Gluten ataxia

Nottingham and Sheffield are about 30 miles apart. If you have neurological problems presenting as ataxia and live in Mansfield you can either go North to Dr Hadjivassiliou's group, who will undoubtedly work you up for gluten induced problems.

Or you can go South to The Queen's Medical Centre, where you may not get worked up in the same manner. In fact, this letter to the editor of the journal Brain is about as critical as respectable doctors get of each other in public.

It is particularly notable that the main reference cited by Wills and Unsworthy for the incidence of coeliac disease only tested antibody positive patients and only accepted them as coeliac if they had intestinal signs on biopsy. Clearly depending on EMA antibodies, as used in Cook's study, missed many patients so the incidence of intestinal coeliac disease MUST be underestimated.

"The value of EMA as a screening tool is therefore limited"

Still, an incidence of 1% is massively higher than was the accepted incidence 20 years ago. This estimate will continue to increase as people realise how widespread the problems from wheat are.

Backing away from intestinal disease as a pre requisite for gluten problems:

The whole point of Hadjivassiliou's work is that there may not be ANY gut signs with neurological gluten induced disease.

We know full well that the zonulin system in the gut is disrupted by gluten. This is irrespective of the presence of intestinal coeliac disease. Once the gut is permeable to proteins you can take your pick of auto immune diseases. If you get neurological problems AND gut problems Nottingham might accept that you have gluten ataxia. If you get neurological signs without gut damage then it's time to get in your wheelchair.

Sheffield will drive you to a gluten fee diet. It might just work.

If I lived in Mansfield and had some weird neurological disease, personally I'd head North to Sheffield.

Peter (Born in Nottingham but Sheffield is good, just don't take your car)

Low fat moods

These two papers caught my eye. The first is observational and uses very limited in data points but clearly suggests the hypothesis that sugar is a cause of major depression. The biochemistry is supportive of this, a high carbohydrate meal increases blood insulin, which increases blood tryptophan, which increases brain serotonin.

So you fall asleep after a high carb meal.

I used to be a standing joke in our family before I went LC. One of the joys of avoiding rice and pasta was getting my evenings back. The aftermath of sleeping through a serotonon spike is that about three to six hours later your brain serotonin plummets and you can't sleep. Ah, those nights of looking at the clock every five minutes from 2am to 4.30 am. The switch to LC not only gave a good night's sleep every night but I woke feeling good each morning. That's better.

So I find it highly plausible that sugar causes depression. Kick your serotonin system often enough and it will go on strike. Or develop "serotonin resistance" comparable to "insulin resistance".

The second paper looks at the effect of a low fat diet on mood. The abstract is self explanatory and here are the important lines:

"ratings of anger-hostility significantly increased in the intervention group after 1 month on the low-fat diet"

and this

"The results suggest that a change in dietary fat content from 41 to 25% energy may have adverse effects on mood"

One month is VERY rapid for a mood disorder to emerge. Healthy volunteers are not usually prone to anger hostility episodes. This is an intervention study with the subjects acting as their own controls. It's good.

Next time you get carved up in a minor road rage episode, just ask yourself if the perpetrator will have had bacon and eggs fried in butter for breakfast. Alternatively perhaps a bowl of sugared cereals lubricated with skim milk followed by toast and jam lubricated with a low fat spread. Probably has a heart problem and is on a statin too. Anger hostility rating? Is this problem growing?

Dr Ancel Keys again?

Peter

Obviously what is missing from the second study is a period when the subjects ate 80% fat in their diet. I assure you it feels good.

Getting fat is bad when you stop

There comes a point beyond which getting fat becomes counter productive. This happens when you are too fat. What do I mean by too fat? Being fat is supposed to have survival benefits... I was thinking along the lines of type 2 diabetes, an enormously complex disease.

This problem is obviously "associated" with obesity, yet most obese people do NOT develop diabetes. Plus many thin people can and do develop type 2 diabetes.

From my perspective I think that type 2 diabetes occurs when people loose the ability to put on any more fat. This can happen at assorted body sizes, not just the seriously obese. In fact a huge person who is still gaining weight may well be safe.

We know that obesity requires just a small excess of fat per day to be locked in to adipose tissue by the insulin produced in response to dietary carbohydrate.

That's fine for a few tens of years. But there are limits on both the number of fat cells and the size to which they can be pumped. Eventually they get so full that they just say NO to any more fat. Bearing in mind that it is insulin which puts the fat in to fat cells, the easiest way to say NO is to refuse to put out any insulin receptors, the phenomenon of insulin resistance.

What happens when a fat cell refuses to listen to insulin's storage message? Well, it allows hormone-sensitive lipase freedom from insulin's restraint. This results in an outpouring of the energy set aside, over many years, for a rainy day which never came. Non esterified fatty acids (NEFA) in the plasma increase rapidly. NEFA are the high energy rival to glucose for cell power supply. The control of NEFA flow is at their release point (fat cells), not their uptake point. When the adipocytes thumb their nose at insulin, they release a flood of inappropriate energy which is taken up by just about every cell that can remotely use NEFA for fuel.

Packing NEFA in to cells beyond their wildest possible needs means that they have no logical use for glucose. Muscle tissue is the primary "sink" for glucose. Muscles love NEFA. Once they are packed with NEFA why should they accept glucose? They just say NO by becoming insulin resistant too. If there is no where for glucose to go, it builds up in the bloodstream (especially if you live on bagels and waffles) and you get the label of type 2 diabetes.

Much of this I worked out by slogging sentence by sentence through Dr Raz's article here. He gets hopelessly lost in ideas on treatment. His basic idea is that because the problem is one of excessive fat storage (it is) and the stored fat is from dietary fat (it is) then the correct approach is to reduce dietary fat (WRONG). The correct approach is to reduce the hormone which is causing the excess storage. That is insulin. The spectacular success of low carbohydrate diets for management of type 2 diabetes clearly show this is the way to go.

As soon as you drop insulin levels the fat cells, no longer over bombarded with the message to hyper-inflate themselves, start to listen to the voice of reason. Basal insulin can inhibit lipolysis to levels appropriate for energy needs of the body. Blood glucose normalises because the bagels are in the bin, not your bloodstream. Lipolysis without carbohydrate overload allows ketosis which controls appetite.

I also had some fun with this paper, which gets the prize for worst title ever on a diabetes paper.

Please Pass the Chips: Genomic Insights into Obesity and Diabetes

I guess that the chips are bits of information. I couldn't find anything in the paper about what I would call chips. It is an American paper so I guess they would have used the term French Fries if they had really meant chips... Still, an appalling suggestion for a diabetic diet.

Anyway. The paper has some interesting points. Ignore all the garbage about micro arrays and gene switching etc etc. Throwing money at a problem does not always mean that you understand it.

No, they discuss the lipodystrophies, spontaneous in humans and engineered in lab animals. The basic message is:

Total absence of fat cells equals severe type 2 diabetes, in an organism without any fat at all.

No fat cells means nothing to listen to insulin, so nowhere to store energy. The lack of adipocytes is the equivalent of being born with 100% ineffective adipocytes. If you have no storage space you have to shove your dietary fat in to whatever tissue will take it. Once the tissue, particularly muscle, has a generous supply of fat it will, as above, say no to glucose.

So, as I see it, type 2 diabetes is a condition where adipose tissue cannot accept energy, either through years of hyperinsulinaemia or because it never actually formed. The end result in both cases is muscle fatty acid build up to a level which causes glucose refusal.

You then pee the glucose down the loo. Or eat LC and fix your problem. If you have a lipodystrophy I'm not sure how effective LC eating would be, but it certainly works for standard type 2s.

Peter

Getting fat is good

After discussing the two rat experiment and applying it to Kitava, it must be pretty obvious that getting fat in the good times improves your chances of surviving the lean times.

Being fat is good for you.

Anyone going in to the next poor harvest with a BMI of 18.5 is significantly less likely to come out alive for the next good harvest than someone of BMI 29.9. Thinking Kitava here, same applies to hunter/gatherers. But is it possible to have too much fat?

Well a BMI of 18.5-25 is considered "ideal". Looking at this paper we find that:

"Overweight was not associated with excess mortality (-86,094 deaths; 95% CI, -161,223 to -10,966)"

That is BMI 25-30 has lowest all cause mortality. Lower mortality than our ideal target range. Perhaps it's time to move the goal posts. Maybe BMI <25 should be a cause for concern. I'm in trouble on that one!

My only consolation of running my own BMI at 20.5 is that being slim on a high fat diet is almost certainly not as bad for you as when you are on a carbohydrate based diet. It may be good for you. No one will ever find this out looking at USA health statistics. On their Food Pyramid everyone suffers.

Peter

PS I tried to understand this paper in depth and it is strictly for the statisticians. I'll have to take Katherine Flegal's word for the results being true.

Professor John Yudkin and Dr Ancel Keys

Here's a page or so (p163-4) from John Yudkin's book "Pure White and Deadly", 1972 edition. Yudkin begins the chapter with an apology for talking about such uncomfortable disagreements in public. But he liked the truth.

This quote covers opinion from Prof John Yudkin and Dr Meyer Friedman. You can hear their dislike of Keys. Keys was the architect of what has become the current world obesity epidemic and never one to let the truth get in the way of a good idea, as with his six nations "fat causes heart disease" study. Unfortunately Meyer's list of those easily misled did not include gullible politicians who set food policy. Keys was a very successful politico, with intense conviction of his own correctness. Fine if he had been right, which he wasn't.

Yudkin begins:

I have already mentioned Dr Ancel Keys and his pioneer work in relation to diet and heart disease. A year or so ago he wrote a memorandum which he sent to a large number of scientists working in this field and which with very few changes has now been published in a medical journal 'Atherosclerosis'. It consists entirely of a strong criticism - I nearly said virulent criticism - of the work I have published from time to time on the theory that sugar is the main dietary factor involved in causing heart disease.

The publication contains a number of quite incorrect and unjustified statements; for instance; that we had never tested our method for measuring sugar intake; that no one eats the amounts of sugar that we and others have used in our experiments; that it was absurd of me in 1957 to use intemational statistics of 41 countries as evidence for the relationship between sugar and heart disease (exactly tbe same statistics that Dr Keys had previously used for only 6 selected countries to show the relationship between fat and heart disease).

He ends by triumphantly pointing out that both sugar and fat intakes are related to heart disease, but that the cause must be fat, not sugar, because he had just found in 1970 that fat intake and sugar intake are themselves closely linked. You will remember my own discussion of this link in Chapter 5, based on the fact that, as far back as 1964, I had shown this relationship to exist between fat intake and sugar intake. Let me therefore quote from a recently published book Pathogenesis Of Coronary Artery Disease written by Dr Meyer Friedman, another distinguished worker in this field:

"It is sad, for example, to observe that essentially honourable investigators omit published data (including some of their own data obtained earlier) which refute or call into question their contemporary data and the interpretations they have made of them. It is even sadder to observe how these same observers eagerly and indiscriminately collect studies (no matter how poorly or incompletely performed) supporting their respective hypotheses but peruse with the most "nit-picking" and distrustfuI eye other studies which tend to subvert the interpretive verity of their own. But this is not really a very important cause of our present confusion because only a few investigators indulge in these practices and their foibles are quite well known to their scientific peers. They essentially succeed in misleading only themselves and those physicians and laymen who can not be expected to know of the self-imposed enslavement of these investigators to their respective concepts"

Hmm, Friedman on Keys sounds like Ravnskov on Keys' modern followers.

Plus ça change (plus c'est la même chose)

Peter

Two rat experiment

While I'm talking about fat I ought to just run through the two rat experiment described by Daniel Quinn.

You place a breeding pair of rats in a very large cage with, let's say, 5kg of rat food. At the end of 24 hours you remove any left over food, put in a fresh 5kg and repeat the process ad infinitum. Remove the excess, never allow more than 5kg. Clean them out occasionally.

They will breed. Their children will breed. Their children's children will breed. The population will grow. Eventually there will come a day when there is no rat food spare at the end of 24 hours. The young rats will continue to grow, maybe some of the older ones will die, those in their prime may loose a little weight. That's life for rats in the cage.

Ultimately an equilibrium will be reached between 5kg of food and a dynamic population of rats. That population will not fluctuate wildly.

You cannot make new rats out of thin air. Older rats dying will free up some food supply so more youngsters will survive. It will balance out.

This was exactly the situation for the humans on Kitava when Lindeberg did his study. On an isolated island, using limited subsistence agriculture and no external power or fertiliser input, there must be a balance struck between population and food.

Back when everyone on the Earth either subsistence farmed or hunted/gathered the same situation must have applied. Hunting on the neighbouring tribe's patch might be highly unpopular and this would set limits on food availability, even with a full continent to use. People were everywhere that would support life.

I don't think that continuous hunger was ever the norm, but obesity would be unheard of. A sustained glut of food would produce extra sprogs to take up the slack. Hard times would be hard on the vulnerable. We humans did this successfully for millions of years. We are no different to rats. We can only breed to our food supply, but we always will breed to that supply.

There never was enough spare food for obesity until the Egyptians started with storable Spelt. It all went down hill from there.

Peter

Getting fat, staying fat, follow on

One kilo of lard contains 9,020kcal of energy. A chunky 40kg of lard represents 360,800kcal.

In the simplistic world of calories-in versus calories-out, how many excess calories per day is this, spread over a reasonable weight gain period? Let's assume it was gained over 20 years, or 7,300 days, ignoring leap years.

That gives 49kcal/day of stored fat. If calories-in equals calories-out anyone carrying 40kg of excess weight could have stopped it by eating just one tiny spoonful less of butter per day. EASY. For goodness sake, these people must be such weak willed, greedy slobs that we should withdraw NHS medical care until they get their act together and stop pigging out on a spoonful of excess butter per day.

But just a minute, how many obese people WANT to be obese? If you believe the calories-in calories-out drivel, weight loss should be easy. Anyone can back off this much butter. Weight Watchers would go bankrupt.

But telling an overweight person to avoid eating fat (gasp, all those calories per gram) means that their diet must be based around carbohydrate. Which raises insulin. Which blocks fat loss. Just 49kcal of blocked fat loss each day over 20 years equals an obesity epidemic. It's not the calories from dry bread, spread with low fat goo, that does this but the insulinaemia that goes with it.

Most people do not read biochemistry texts for fun, they expect their nutritionist to have been paid to do that.

Peter

PS How DO people loose weight on low fat diets? They eat low everything, get hungry and dip their insulin low enough between meals to loose weight, especially in the early hours of the morning. This is hard, especially to sustain. Fat is your friend when you want to loose weight. No hunger in ketosis.

Getting fat, staying fat

Fat gets in to fat cells from lipoproteins in the blood stream. Dietary fat is transported in chylomicrons, big fat ladened lipoproteins made by the gut wall. Their production is as random as fat consumption is variable.

Our the bodies never just move fat molecules intact. They are always broken down in to fatty acids, moved across cell membranes in this form, and then reassembled in to triglycerides for long term storage.

The enzyme which performs this break down process is called lipoprotein lipase. Lipoprotein lipase is thus essential for fat storage. That's important.

Fat breakdown, for use as an energy supply, is performed by a completely different lipase, this time it is hormone-sensitive lipase. This enzyme acts on the stored triglycerides inside fat cells and releases free fatty acids in to the blood stream. This is a highly regulated process, finely tuned to supply the energy needed by the body. It is very different from the bulk transport of dietary fat in lipoproteins. As such, the fatty acids can be transported in free form called non esterified fatty acids (attached to albumin in plasma) and simply released as they are needed. Hormone-sensitive lipase is crucial to fat breakdown. That's important too.

It is very obvious, from its name, that hormone-sensitive lipase is under hormonal control. The only hormone which turns off this lipase is insulin.

This paper (From way back in 1964, this is not new information. Physiologists asked very basic questions in those days) shows clearly that insulin, at levels way too low to do anything related to glucose, stops the release of fatty acids from fat tissue. So anything which raises insulin levels blocks fat break down. Carbohydrate raises insulin levels. Insulin blocks fat breakdown. Carbohydrate blocks fat breakdown.

Back to that other lipase, the one that puts the fat in to fat cells in the first place. Is that under any sort of control? Of course it is, our bodies control everything. Guess which hormone controls lipoprotein lipase.

Yes, insulin again.

So insulin has two effects on body fat. It puts it on and keeps it on.

But dietary fat, the primary source of the fat we store, has absolutely no effect on blood insulin levels what so ever. You can eat a block of lard and not budge your insulin levels one iota (or a cup of cream, much more enjoyable). What causes us to store dietary fat, as a big bum or tum, is dietary carbohydrate, because it elevates blood insulin level more than any other food source.

So the take home message from this post is that insulin is the key hormone for fat storage. Dietary carbohydrate makes you store dietary fat, and eating carbohydrate stops you burning stored fat.

It makes you think of those Swedish children. Eating sugar makes them fat, eating saturated fat keeps them slim. Now you know why.

If only nutritionists understood this.

Peter

PS does eating half a kilo of lard per day make you put on weight? Possibly, as there is a basal rate of lipoprotein lipase activity irrespective of insulin levels. More importantly, have you ever tried to actually eat 500g of lard in a day? Palatability apart, if you did actually succeed, you would feel dreadful and I doubt you would be tempted to repeat the experience. The vast majority of people on mildly ketogenic high fat diets seem to stabilise their food intake somewhere between 1500 and 2500kcal/day. That is appropriate for weight loss or weight stability, depending on your baseline weight and activity level.

Sugar poisoning

I don't think much of the cholesterol hypothesis. OK, it's junk.

But I do find cholesterol levels interesting, in so far as they reflect the degree of carbohydrate poisoning a population is suffering. Researchers are starting to understand this, though I guess they still think the cholesterol levels really matter, rather than looking at the primary problems with glucose and insulin. Obviously low HDL and high triglycerides are appalling things to have because, in general, they represent sugar poisoning.

A chink of light occurred with this study. It's epidemiological, observational and not available in full text without being ripped off by the American Journal of Clinical Nutrition. So not much use to anyone. But the press release by the group contains one of the best lines I've ever seen and gets 110% for deep insightful perception. Here's the line I love:

"Previous research has identified ethnic differences in cholesterol and other blood fat levels that couldn't be explained by genes, obesity, lifestyle factors or diet, Merchant and his team note, but these analyses usually looked at dietary fat, not carbohydrate consumption"

Woo hoo, now there's a surprise! People are poisoning themselves with glucose and fructose and researchers were absolutely focused on dietary fat. FAT! This is not focus, this is preconceived blinkering.

I quite like this line too:

"Reducing the frequency of intake of sugar-containing soft drinks, juices and snacks may be beneficial"

Obviously elimination is highly preferable to reduction, but these people seem to know what they are talking about, though I suspect they still think of triglycerides in terms of hot fat down a cold sewer.

Actually, the other publication from this group looks very sensible too. I'll stop being grudging and just say THANKS.

Peter

J-LIT update

Here's a quick update on the J-LIT study using low dose simvastatin for primary prevention of heart disease.

My thanks to Stan for pointing out that I missed the six fold increase in risk of CARDIOVASCULAR mortality in the lowest cholesterol group compared to the "normal" (200-219mg/dl) cholesterol group in this study.

There it is in Table 6 on page 1092. For goodness sake, it's on the first line! I must have been asleep when I read the paper:

Cardiac mortality relative risk was 6.23 in patients who's cholesterol dropped below 160mg/dl compared to those with TC 200-219mg/dl.

That is; you are more than six times as likely to be dead of a cardiovascular problem if your TC dropped to a level to make the average cardiologist grudgingly happy.

Boy, when you need cholesterol, you need it.

Peter

Best ever statin study?

I missed this landmark paper last year, full text here. Possibly because, as it continues the demolition of the cholesterol hypothesis, it received absolutely zero publicity. I posted about the J-Litt study here, but this one is even better.

The paper is from the Essen group (in Germany) and describes their study comparing normal dose atrovastatin (10mg/d) with high dose atrovastatin (80mg/d).

Same drug, different dose rates, different cholesterol levels. Follow your patients for a year and have the coronary artery calcification progress tracked by electron-beam computed tomography. This is a reasonably well designed study, except see the "phew" comment below.

How much difference does it make if you drop your LDL-cholesterol to 87mg/dl as compared to 109mg/dl?

I think the answer is technically known as "diddly squat". Or zero, zilch, nuthin, nowt.

The answer as to why is pretty clear from table 3 shown here.

Look at the falls in hsCRP and fibrinogen on low vs high dose atrovastatin. They're the same between groups. Ie the anti inflammatory effect and anti thrombotic effects are maxed out at 10mg, so no further benefit is seen at 80mg. From my point of view this is fortunate. Had these pleiotropic effects not maxed out the study might have suggested lowering cholesterol was beneficial. But 80mg of atrovastatin is no better an anti inflammatory agent than 10mg is. Phew.

The paper discussion is an amusing catalogue of excuses and references to studies "better" designed to show the benefits of aggressive statin use. The trick is to use different drugs and give the best anti inflammatory statin at the highest dose rate. Then the lowest cholesterol correlates with, but is not responsible for, the least CV problems. It is also sensible NOT to measure CRP or fibrinogen, otherwise you end up with a study like this one, where people can see what's going on.

This group strike me as genuine medics who believe in the lipid hypothesis and are genuinely surprised that they have trashed the cholesterol hypothesis by accident. Still, I'll leave them with the best line from their conclusions, ignoring the squirming in the discussion and the plea for more time to get an effect. Here it is:

"we did not observe a relationship between on-treatment LDL cholesterol levels and the progression of calcified coronary atherosclerosis"

Peter

Thank you to Dr Davis of Track Your Plaque for citing this unheard of paper

and to

Drs Axel Schmermund, MD; Stephan Achenbach, MD; Thomas Budde, MD; Yuri Buziashvili, MD; Andreas Förster, MD; Guy Friedrich, MD; Michael Henein, MD; Gert Kerkhoff, MD; Friedrich Knollmann, MD; Valery Kukharchuk, MD; Avijit Lahiri, MD; Roman Leischik, MD; Werner Moshage, MD; Michael Schartl, MD; Winfried Siffert, MD; Elisabeth Steinhagen-Thiessen, MD; Valentin Sinitsyn, MD; Anja Vogt, MD; Burkhard Wiedeking, MD; Raimund Erbel, MD

for this excellent study, published in a full-text-for-free journal.

Torcetrapib again

I posted on torcetrapib here but missed some information. You always miss some interesting facts when you don't have the full paper. Those nice people on the HDL forum never mentioned the increases seen in deaths from cancer and infection. Fortunately that made it in to the NY Times recently.

Quote from the NY Times article:

"Besides having more heart problems, patients taking torcetrapib were more likely to die of cancer and infection than those on a placebo. In all, 93 patients taking torcetrapib died, compared with 59 who took a placebo"

and from Dr. Daniel J. Rader of the University of Pennsylvania:

“It appears that HDL evolved as a component of the innate immune system and that its composition is critically important to its function.”

Dr Rader gets this week's prize for least well read cardiologist. It's the LDL that matters! But how many cardiologists would read Ravnskov? After all he is one of the most effective critics of the lipid hypothesis. Would you, as a cardiologist, read papers by someone convinced that yourself and the rest of the cholesterol industry is wrong?

Cholesterol and both arteriosclerosis and infection

Cholesterol and cancer

Note that Ravnskov explains all three of the problems seen in the Illuminate trials.

Again a quote from Dr Rader via the NY Times:

"But over all... it is premature to announce the death of CETP inhibitors on the basis of the torcetrapib experience alone"

My opinion?

He's wrong.

Peter

Maria Thommessen

Maria Thommessen PhD was a prominent Norwegian/international nutritionist. She sadly died of bowel cancer in 2006, aged 47, having fought the disease for 6 years.

Here is a translation from the norwegian (again thanks to Jakob from the AHOA forum) which sums up, for me, the tragedy of a highly intelligent person who has dedicated their life to preventing disease though diet, but has ended up in a wrong paradigm. The one fully backed by mainstream medicine. Her certainty is what keeps me looking for the possibility that I might be horribly wrong to eat high fat, low carbohydrate.

Maria Thomessen:

"I wanted to show that you could think positive thoughts and be optimistic even with such a diagnosis. I was very convinced that I should be able to win this battle. It feels like a paradox that it was I that got cancer. I don't think many have eaten as many carrots as me"

Sigh.

Selling fiber and bacteria

I watch the Simpsons. I consider it essential viewing for the maintenance of sanity. Apparently an awful lot of people with either IBS or "normal" constipation do too, judging by the marketing wizards' placement of advertisements for probiotics and/or soluble fiber in the central ad slot. Drives me up the wall. So how effective are these interventions in improving bowel function?

Well, probiotics appear to be very strain related but can have benefits in some situations. Dr Hunter is a gastroeneterologist at Addenbrooks in Cambridge. Taking a combination of bifidobacteria and lactobacillus that looks remarkably like yogurt minimises anaerobic overgrowth when you are on an antibiotic for helicobacter. Fair enough. I ferment my cream with these bugs.

But the role of probiotics in IBS "has not been clearly defined". Probably depends on who funded the study. Certainly lactobacillus plantarum 299v is not too hot.

Lactobacillus casei strain Shirota is pretty interesting according to the company which sells it. Lovely graphics on the homepage BTW. How much did the web site cost? I guess nothing compared to their TV advertising budget.

But are they needed anyway? Two interventions which do work are compared, by Dr Hunter again, here:

Metronidazole (an antibiotic aimed at anaerobic lower bowel bacteria) is pretty good, reducing peak gas production from 671ml/min to 422ml/min. Obviously no one wants to take metronidazole long term in view of its serious interaction with alcohol and its occasional neurological toxicity. But it makes a fairly convincing case that the problem is a bacterial problem. What do bacteria eat that humans cannot digest? Fiber.

So the other intervention is a no-fiber diet. Peak gas production dropped from 564ml/min to 205ml/min. This looks to be very effective and very interesting.

Both improved symptoms. As fiber is of no use to humans and it appears to feed the bacteria that cause IBS, including good old klebsiella, you have to wonder where the medical fascination with fiber comes from...

We all know where fiber ends up, why suffer the gut problems it causes as it gets there?

Peter

How many eggs per day?

Some people like eggs. This man did. Maybe he still does!

Here's a summary as it's not available on pubmed:

Normal Plasma Cholesterol in an 88-Year-Old Man who Eats 25 Eggs a Day: Mechanisms of Adaptation (1991) Kern Jr, New England J Medicine 324(13):896-899

The effect of dietary cholesterol intake on serum cholesterol level is known to vary among individuals. The homeostatic and regulatory mechanisms which tend to keep serum cholesterol constant operate at different levels of efficiency in different individuals. An extreme case is reported here. A physician and colleagues from the University of Colorado School of Medicine have studied an 88-year-old man who, for ill-defined psychological reasons, has consumed 20 to 30 eggs daily for at least 15 years. This individual has maintained normal serum lipid levels and has no history of clinically important heart disease. He consented to participate in a variety of tests of cholesterol metabolism; the findings were compared with those obtained in an ongoing study of 11 normal volunteers who were tested while consuming normal diets and diets supplemented with five eggs per day. It was found that this individual had extremely efficient mechanisms that compensated for his phenomenally high cholesterol intake. In particular, he absorbed only 18 % of the cholesterol that he consumed; the comparison subjects absorbed 54.6% when on low-cholesterol diets and 46.4% when on high-cholesterol diets. He also showed a doubling of the usual rate of conversion of cholesterol to bile acids, moderately reduced cholesterol synthesis, and a possible increase in biliary cholesterol secretion. "These physiologic adaptations would leave little if any of the dietary cholesterol to elevate plasma cholesterol levels and be deposited in arterial walls."


That's assuming you subscribe to the cholesterol myths anyway. I have to say six egg yolks is my normal daily consumption, only occasionally does it reach nine in a day. Never 25, at least so far...

Thanks to Jakob on the AHOA discussion forum for the above text.

Peter

Arteriosclerosis and saturated fat

Observational studies are useless for proving anything, but they do provide interesting starting points for speculation. They can also give some interesting insights in to human behaviour. I particularly enjoyed the American Paradox study.

On the raw data a high intake of saturated fat didn't quite reverse the women's arteriosclerosis, but after modeling it did. Modeling appears to involve adjusting your results to estimate what the values would have been if your patients didn't smoke, didn't have diabetes, didn't eat cholesterol (gasp) etc.

Glancing through the patient characteristics in table 1 you can see why adjustment might be needed.

Look at smoking. The high saturated fat group had the highest percentage of smokers and a hugely higher pack-years value (34 pack-years) than any other group (all below 18). They boozed the most, ate most trans fats and pooped the least fibre. They may even, wait for it, have eaten an egg a day! On the plus side they obviously had the highest HDL cholesterol and lowest triglycerides, because they also ate the least carbohydrate.

If you had to describe this group in one word it would have to be "naughty". These naughty people did all the WRONG things (according to the AHA) and, after adjustments, began the reversal process of their IHD. Thumbing your nose at the AHA, even in this mild manner (by my standards), looks to be good for you.

The lowest saturated fat group had the highest carbohydrate intake, let's call them the Goody Goodies. They made excellent progress as coronary bypass fodder.

Just observational. But what an observation of disobedience!

Peter

How toxic is wheat?

Well, the first point is that Wheat Germ Agglutinin (WGA), the main lectin in wheat, is an insulin mimetic in tissue culture. A very good insulin mimetic. If you want to give someone, male or female, that "ten-months-pregnant" look you can either use masses of insulin, as produced by an insulinoma or perhaps have them take an insulin mimetic like WGA by mouth with every meal...

But does WGA, a protein, cross from the gut in to the blood stream intact to then have a biological effect? Well, that depends on who you ask and what dose you give. Pusztai, funded by the Scottish equivalent of DEFRA, says that, at high doses, WGA not only crosses in to the blood stream but also glues itself to the lining of blood vessels and lymphatics. I cannot think of a better way of producing an autoimmune vasculitis than sticking WGA to your blood vessels. Or of producing a massive insulin like effect, ie beer gut.

Another group of researchers, funded by the Italian government this time, say WGA doesn't cross their artificial model of the gut lining. They also found WGA wasn't heat stable, in contrast to Pusztai. But both groups do agree that WGA trashes the gut lining cells.

So these two research groups disagree about the penetration of wheat toxicity in to the body, but neither argues with the toxicity per se. I believe Pusztai is correct, especially for those poor people who regard wheatgerm, with its lectin load, as a health food. Apparently they take it in multigram doses. No thanks.

That's before we consider the effect of gliadin from wheat on gut permeability disrupting the tight junctions between enterocytes. Damaging the integrity of the gut allows all sorts of dietary proteins to gain access to the blood stream and, obviously, the immune system. I guess it helps WGA in to the circulation too.

It probably helps the two insulin stimulating peptides derived from the partial digestion of gluten in to the blood stream too.

It probably also helps WP5212 in to the path of the immune system of potential type one diabetics, allowing them to achieve their full disease potential.

I won't mention coeliac disease and schizophrenia. Or gluten ataxia. Or a host of other problems.

Today a drug rep provided pizza for lunch at work. I ate my chocolate and drank my fermented cream sitting alongside the 4 giant pizzas in the rest room. Several people asked if I wasn't tempted to indulge.

Too much information, too much toxicity and ZERO temptation.

There is no doubt about the toxicity of wheat.

Peter

Lipoprotein(a) and oxidised cholesterol

Lipoprotein(a) is a subgroup of LDL cholesterol which has had an extra protein added to it. This extra protein is sticky, particularly to the lysine and proline residues of collagen which get exposed in damaged arterial walls. Like LDL cholesterol, it is a method of applying a sticking plaster to damaged vascular endothelium. If you have lots of damage to your arteries you would expect your liver to make lots of lipoprotein(a). It's not stupid. Lipoprotein(a) is especially needed if you have defective LDL receptors, so in familial hypercholesterolaemia you would expect lipoprotein(a) to be high. That's what you find. Using a second choice repair system is likely to be associated with a poor repair and so with heart disease. It is. Oddly enough, if you live long enough this extra repair system becomes rather important and centenarians have rather high levels of lipoprotein(a). So it can't be all bad.

Anyway, a quick google or pubmed search on lipoprotein(a) will tell you that that it is a risk factor for heart disease (now there's a surprise) and that your blood level is genetically determined, so there's nowt you can do about an elevated level anyway. Wrong.

In the simplistic world of cardiology you lower blood lipids by lowering dietary fat. Under this intensely stupid idea it is impossible to lower lipoprotein(a) by dietary means.

Of course you could still go on and try that low fat idea. The Finns tried it. They, like most of the world, follow the low fat line in heart disease prevention. Just take 37 women who are already down at 70g fat per day (appallingly low to begin with) and reduce it to either 56g with minimal veggies or 59g with lots of healthy veggies plus nuts. Then flip the diets in a crossover study. Let's see what happens to lipoprotein(a). Both diets crank up lipoprotein(a). The 56g low veggie diet increase lipoprotein(a) by 7%. With those lovely veggies it cranked up by 9%. Note, another confirmation that fruit and veggies are BAD.

The converse has been nicely done. Just use a LC diet and lipoprotein(a) drops by 11.3%

Genetically determined hey? Duh.

Oh, and look how the low fat diet, with or without veggies, oxidised the LDL cholesterol. Low fat diets are very nice if you are in the cardiac business. As these squirming editors seem to be. What a load of twaddle. Bad is good. Really. It's good. Really, bad is good.

How many fingers, Winston?

Peter

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