Update

Well, we're moving to Glasgow, the coolest, cloudiest and probably most UVB deprived city in the UK. But it does have some advantages. Despite there being no surf within easy access, there are rivers which are quite impressive.




This is the Orchy, the picture is of me in a miss spent youth (circa 1977ish) and it had been raining for a solid month, so a normal August in the hills north of Glasgow... I still remember vividly the feeling of paddling round the first bend below Bridge of Orchy, in the middle of a river as big as the Trent in full flood, and realising that it went down hill in front of me, rather steeply, and there was nowhere to go except down... Thank goodness for brown underwear.

So life is a mix of building work, chasing nurseries, chasing rental accommodation, organising a trip to start house hunting, chasing a plumber, builder, plasterer, finding the shower unit won't fit the bathroom, starting to ebay the shower and my motorcycle, rehoming the chickens (tragic this aspect, what will Squiggs do with no Penelope chicken to cuddle, the cats are worried). You know the stuff... There seems to be an inordinate amount of cutting and stitching to do at work too.

By hook or by crook my wife's pathology residency starts 3rd of August in Bearsden and I've handed notice my notice in for 17th July. It's a little tight! But very exciting.

Peter

Sabbatical

I was looking for Mary Enig's "Know Your Fats" on the bookshelves a couple of days ago and came across my unopened copy of Edward Tenner's "Why Things Bite Back" next to a 2/3 read copy of "Mistakes Were Made", an unopened copy of Desolate Landscapes and a recently arrived copy of Prothero's Evolution. John Peel's biography is part read (fascinating and sad to watch the progress of metabolic syndrome through the illustrations!). I have two novels from my daughter, unopened since Christmas and there's my wife's copy of Neverwhere that I'd love to read. I also keep getting emails from Lovefilm to ask why it takes me a month to watch "Iris".

This is trying to tell me something.

I've also finally accepted to an invitation to speak to a group on diet and health in the near future, which will be a fair undertaking. Plus we have to have the house sold by the end of July which is not a minor objective.

So I think I may be going to have to take a bit of a sabbatical from blogging in the next few months, until we are settled in to wherever the post PhD job market takes us and I have found work too.

Sorry for this, but stuff creeps up on you and you need to think, read and live, as well as blog!

As Richard commented off blog, there will always be papers I can't resist a two liner on (like the last one on AMI) but there is just too much to get done...

Back in the Summer, all things being equal

Peter

EDIT: The comments thread on this post has been used by a proponent of a particular view of life which is labelled, by them self, as the HED, the High Everything Diet. I'm leaving the comments in place as they are fascinating in their own right. A reasonable but slightly overgeneral idea of what I personally feel is going is available here.

Please bear in mind that it looks like, while the proponent is mentally unwell, he is also very intelligent and it's YOUR health that YOU are playing with. Play safe on the net.

It's never too late to normalise your glucose (so long as you are still alive)

I've just plotted the risk of being dead in the near future vs post admission glucose for coronary patients in this study. Haven't seen the full text so I've no idea whether there was an acute drop in LDL cholesterol in the survival patients, to keep cardiologists happy, but I guess not or they would have mentioned it. In fact, if you had to guess, you could do worse than to guess that an acute drop in LDL would come accompanied by a black cloak and scythe.

Anyway here are data from the abstract in graph form. Enjoy.


Although it is possible the hyperglycaemia is the problem per se, it is equally possible that it simply reflects underlying insulin resistance. But I doubt anyone is going to ask for an IV glucose infusion plus some diazoxide post MI to find out!

Peter

Cholesterol within nations studies

These are the slides from the within-countries discussion on cholesterol and heart disease. I've allowed the sarcasm back in, which was strictly limited when the slides were originally presented. OK, there is a correlation. In fact, if you are a bloke, having a cholesterol above that certain magic number on the graph is clearly catastrophic and boy, are you in trouble. No statins to save your life in those days!



But what is the mystery number which sentences you to cardiac death? Obviously the original Framingham study did not use a random scale. But the scale used in the study was highly non linear. Here is the same graph with the real numbers added.



Once you have realised quite how unlinear the scale is I would just like to draw your attention to that number on the bottom right written in RED. No, it's not a typo. That really is 1124mg/dl. Okaaaaaaaaay. Hands up if you think a TC of 1124mg/dl is part of a normal distribution of cholesterol values in a "normal" population. Are there any conditions which elevate cholesterol and increase the risk of heart disease? Answers on a postcard to any endocrinology department you happen to know the address of.

Anyway, next thing to do is to linearise the scale. I've been kind and left the upper data point in the middle, not placed it at the upper end, of the range quoted:




Now here is my main cheat, and I admit it's a cheat. There must be a population towards the upper end of that last data point who have medical problems to give them an increased risk of heart disease. Cushings Syndrome and hypothyroidism are two for starters. So I would argue that it is only fair to the representatives of this subpopluation that the risk scale is extended up for their benefit. 100 "events" per 1000 in this group seems possible, hence the extended scale:



So let's go back and look at the initial random points and leave the top cholesterol data point where it belongs, about a yard to the right of your screen:



Ah, that's better. Some semblance of honesty now. But again, not quite as convincing as the first graph. BTW did anyone notice that the left hand scale was events, not deaths?

Did the Framingham investiators look at deaths? Hahahahahahahahahahahaha bonk. Sorry, that's me laughing my head off. Of course they did. There is no association between elevated cholesterol and increased cardiac deaths, but the trend is that high cholesterol is protective. Luckily for the Framingham researchers they were underpowered to detect this. A whiff of the low powered studies we see nowadays.

Now let's just look at the MRFIT screenees. These are the many, many people who were looked through before cherry picking the victims for the MRFIT intervention trial which, incidentally, killed more people in the intervention group than died in the the usual care group. Luckily (again) this did not reach statistical significance, though it may have been of some biological significance to those extra people who ended up dead in the intervention group.



The original study had non linear group sizes (like Framingham) to specifically, oh, I mean accidentally, obscure the effects on all cause mortality in the low cholesterol individuals. The graphs above are taken from a later sub-analysis by a rather more honest and objective lead researcher. Such people do exist in cardiology.

The other hysterical aspect of these graphs is that the original data presented from the MRFIT screenees wasn't, wait for it......

It wasn't corrected for smoking!

Yet another re-analysis shows a marked association between TC and cardiac deaths, but only in smokers. About what you would expect if LDL cholesterol was doing its best to repair smoking induced damage and failing.

The association is still present in non smokers and is statistically significant but so much weaker that the biological significance is highly debatable. It probably represents sucrose intake.

So in summary, the original MRFIT screenees study (presented as the clincher for cholesterol causing heart disease) obscured the scary aspects of low TC and, err, forgot to correct for smoking!

Don't you love the foundations of modern cardiology! Can't sum up MRFIT better than Dr Werko.






For a breath of fresh air it's worth going to Norfolk in the UK.



This innocent little graph is plotted from the EPIC Norfolk data. Now I'd hate to suggest that being hyperglycaemic has anything to do with heart disease, but you can read the graph as well as I can. Association not causation. And of course we know that eating fat causes hyperglycaemia, just ask any diabetologist. Shrug.



The weird thing about UK researchers is that they give you the raw data, it's not a matter of a little table of regression coefficients corrected for this, that and the other. You can read the results tables and plot the graphs. They even give you raw smoking data. And of course you get both TC and that evil killer, the LDL level. Let's plot them on the same graph as the HbA1c vs relative risk of cardiac events.



Personally I'd be looking to minimise my HbA1c rather than my LDL-C.

But then I would say that.

Peter

In the gym

We were discussing weight and BMI at work and the secretary who has named me Tigger was pretty adamant that that I was at least 2kg too skinny. I thought about it for a while and decided she was right so I'd set up a gym at home and see if I could put on a couple of kg of muscle, rather than fat. In general all of my exercise is opportunist at the moment. So here's the gym:



I can just lift one end of this railway sleeper and lever it to above my head. My workouts consist of moving moving it about. I spend about 30-60 seconds a day doing this. Been doing it for about a week and, despite muscle gain, I've dropped below 64.0kg for the first time in ages. I'll give it a month and see how I feel. So much for using exercise to gain weight!

Peter

Fructose, Glucose and Cholesterol

This paper came my way via Eddie Vos, through a discussion in the THINCS group.

OK, what's going on in the paper? It's the metabolic ward study to end all metabolic ward studies. Routine criminals who volunteered to live in a "food proof" prison and to eat a diet based on pure chemicals. This is a prison within a prison:

"The described study was conducted in an especially isolated wing of the California Medical Facility (CMF), a state institution for adult male felons. The isolated area included large indoor recreation, lounge, and shower areas, and 24 individual cells, and was so located as to prevent completely the passage of any food through or near the area."

And what yummy food did the inmates receive?

"These diets were unique in that a) their essential and nonessential nitrogen source was provided exclusively in the form of optically pure L-amino acids and b) they were administered as single, crystal clear aqueous solutions that were nutritionally complete in themselves. In essence, the diets were composed of balanced (but varying) proportions of L-amino acids, the required water-soluble and fat soluble vitamins, the pertinent mineral salts, glucose or other simple sugars as the source of carbohydrate, and ethyl linoleate as the source of essential fat."

Apparently the various versions of the diet all tasted disgusting, for want of a better word.

Apart from the interest of human experiments along these lines, there were a few other tweaks they applied. First we have to note that these diets were essentially ultra low fat diets, the same family as the diets used by McDougal and co. There is not a grain of white rice which does not end up as blood glucose. If you eat brown rice there is a split between the fibre and the minerals it is depriving you of (you know where they get flushed) and the starch, which ends up as blood glucose. So these are seriously low fat, high carbohydrate diets.

What happens when you feed an elemental diet based on glucose alone as its calorie source? Blood cholesterol drops, from a normal value found in a non statinated male of 227mg/dl (while eating 1970s style prison food), to a cardiologic near Nirvana of 160mg/dl. Replacing 25% of the glucose with sucrose produces a rise in cholesterol to 208mg/dl. Removing the sucrose and going back to pure glucose drops the cholesterol level back down to 151mg/dl.

Is that good or bad? You need to remember the old adage that the best cholesterol level is one that has not been measured. But what is happening probably goes back to that short section of the ApoB100 protein which glycates particularly easily, discussed here. I think it is worth pointing out again that fructose should never penetrate in to the systemic circulation, so its whole body damage should be indirect. It probably does this through the induction of hepatic insulin resistance. Fructose has to be metabolised immediately and the end result is raised intracellular hepatic triglycerides. We've seen before that a decent supply of intra cellular lipid makes a cell say no to glucose and that it does this by exhibiting insulin resistance. The liver normally stores glucose in response to insulin. Rendering it insulin resistant would logically stop it storing glucose and pour the stuff out in to the systemic circulation...

That's the basis of this post and it needs bearing in mind when we look at cholesterol variation and heart disease with a given population. But there's an aside first that really creased me up...

A quick pubmed looking for a reference to fructose and insulin resistance (there are hundreds) produced this gem, hot out of cyberpublishing a few days ago.

The group used an antisense oligonucleotide, which is a short section of DNA, RNA or a similar synthetic drug which specifically blocks the activity of a corresponding section of messenger RNA, which means the the relevant gene no longer gets successfully transcribed. By doing this they turned off lipid synthesis in the liver in response to fructose. No hepatic insulin resistance despite fructose intake: Wow!!!!!!!!!! Take this drug and you too can drink Pepsi Max without turning your liver in to foie gras. What else does it do? Oh, it lowers insulin resistance, whole body! Superb, give me some.

Oh oh, it's your butt which soaks up the plasma glucose... As they say of their own technique, it resulted in:

"increased insulin-stimulated whole-body glucose disposal due to a threefold increase in glucose uptake in white adipose tissue"

Translation: "our wonder drug makes you fat".

It is also described as a potential "treatment of NAFLD, hypertriglyceridemia, and insulin resistance associated with increased de novo lipogenesis", I would add "by making you fat". I'd also add that this de novo lipogenesis can easily be avoided by avoiding the fructose in the first place.

What is not remotely obvious from the abstract is: Where does the fructose go to, if it's not used to converted your liver to foie gras?

I guess it's either going to glycosylate your liver (sounds great for longevity) or spill in to your systemic circulation, where it can glycosylate whatever it come in to contact with.... Or it might just overload each liver cell with more pyruvate than it knows what to do with. Now there's grist for the mill of unintended consequences!

Back to the real world:

A fructose intake of 12% of your calories makes your metabolism unhappy enough that it has evolved a technique to increase cholesterol levels under these rather rare (until recent times) conditions. It probably has knock on effects through hepatic insulin resistance resulting in hyperglycaemia and all of the damage that this leads to.

While some fructose is perfectly OK (I too eat home grown fruit in season and a certain amount of sucrose) I suspect a large amount is not OK.

Under highly defined conditions, fructose raises your total cholesterol level.

Peter

EDIT: Sue has pointed out, off blog, that the other reason for a fall in cholesterol is due to minimal production of triglycerides. If glucose is being consumed within the ability of the liver to store it as glycogen there is no reason to convert it to fat and so there is no fat to export as triglycerides. Fructose immediately converts to fat and any fat produced in excess of the needs of the liver will be shipped out as LDL precursor particles, raising both LDL and TC.

Both mechanisms are fructose related but not fructose specific. The average trigs were 93mg/dl but the study did not split anything other than TC by the sucrose/fructose periods early in 19 weeks of the initial part of the diet. The volunteers remained pretty well weight stable throughout, as far as I can see.

So you have a choice of two mechanisms, there may be more, but the association still seems to hold that TC is a marker of fructose intake, with a number of confounders once you get off of chemical diets. BTW the TC went back to a normal >200mg/dl on return to normal food. Or uless you have a TC like mine (and a few other folks), which is a law unto itself.

That FSA apple

It seems that the FSA is suggesting that eating enough fructose will make a maggot eat your heart out! Some sense at last. Oh no! They think that apples are GOOD for you. But a maggot has certainly eaten a heart out of the apple... I suppose it's as accurate as suggesting that the temperature-drop induced phase change from liquid to solid of saturated fat, the one which blocks drains, will also block your arteries. Perhaps the FSA has a heart of ice!

My taxes are paying these idiots' wages!




To quote JohnN:

"What the apple hates anthropomorphically is the relentless human selection that gives rise to the grotesque size and fructose content of its fruit"

I love the concept of apples as grotesque!

Peter

Cholesterol presentation: Between countries

OK, this is the graph of heart deaths plotted against fat intake, produced by Ancel Keys in 1953. It's a beautiful curve, utterly convincing to any Congressperson looking to find fame by funding a cure for heart disease:



Unfortunately Excel doesn't do nice sweeping curves, so I've mangled it by eye to a straight line thus:



Which is still very convincing. Slightly less convincing is when the choice of different countries from the same data bases suggests that dietary fat has nothing to do with heart disease and that heart disease is very rare anyway:



Of course choosing a few other countries might have given a negative correlation:



And, with a little effort, we can see that if only we could just get everyone's fat intake above 40% of calories heart disease would be a thing of the past, just so long as we chose the correct countries to look at:



So let's stop playing and look at the whole database from which Keys carefully selected his six countries:



OK, there IS a correlation. It's pathetic, especially compared to the original line swept in by Keys. Of course things get worse if you add in the Masai, the Inuit, the Rendile, the Tokelau and a few others, shown as red dots:



At this point you would have thought that the name Keys would have become a joke and people would simply have ignored him as a self publicising evangelist with scant respect for the truth. But Keys was nothing if not determined. In 1958, the year after Yerushalmy and Hillebo had shown him to be a charlatan, out came this paper explaining the mechanism by which the high fat diet apparently caused heart disease, even if it didn't. Serum total cholesterol!!!!!! Picture credited to Dr Ravnskov (couldn't get the original).



Of course adding a few data points, which Keys had conveniently forgotten, gives this plot, again credited to Dr Ravnskov:



Anyone for a straight line? These studies are the core of the lipid hypothesis. They are where it all came from and the "science" is total junk.

As a final comment on between nation studies this figure, credited to Dr Kendrick, shows the rates of death from CHD plotted against the percent of a given population who are frankly hypercholesterolaemic. He extracted the data from the little discussed MONICA study:



Obviously living in Russia, Northern Ireland, the Czech Republic or Lithuania is bad news for CHD. Forget cholesterol.

That's as much as there was time for on between nations studies. Essentially they provide absolutely no support for dietary fat or serum total cholesterol as causes of coronary heart disease. It seems impossible that they should have spawned the current climate of cholesterol psychosis, but they did.

Within nations studies comes next.

Peter

OK, time to knuckle down to five very long days at work...

Fructose and heart attacks

Hats off to Dr Briffa for this link. It's Willett of the weird PCOS diet again, but this one is useful. As far as I am aware sweetened drinks are not sweetened with glucose. It's sucrose or HFCS. Dare I use the F word? OK. Fructose. There. I said it again.

You want a heart attack? F.

Peter

Food: African Beef Stew

Just realised I never posted this recipe, the peanuts are distinctly neolithic but the flavour is yummie. Occasionally... It's on the top of the cooker now!

Peter

African beef stew, serves 2, maybe 3...

ingredients:
1 lb diced beef
Tin tomatoes.
Medium carrot, sliced.
Medium onion, chopped.
50-75g butter, depends on how fatty the meat is.
50g peanut butter.
Bayleaf.
About 200ml water, to just cover meat.
Salt and pepper to taste.
Fresh root ginger, however much you like.
3 cloves garlic, crushed
Pinch Cayenne pepper
Pinch ground cloves
Tablespoon vinegar or lemon juice.

Place all ingredients in a casserole, bring to boil, stir well, cover, place in oven at gas mark four for 2-3 hours until meat melts in the mouth. Stir every half hour.

Can be cooked very slowly on top of the cooker.

Fats and absorbing endotoxin

Chris sent me a very interesting link a while ago and it just brought home to me how difficult it is to interpret a study in isolation. In fact, how random the world is in terms of what anyone does or doesn't know.

Bacterial endotoxin is a breakdown product of the cell wall of gram negative bacteria. It's a lipopolysaccharide and even quite small amounts of it are extremely unpleasant. In overwhelming gram negative infections killing the bacteria releases endotoxin which can itself be fatal to the patient. Not killing the bacteria can have the same effect on mortality, so the best advice I can give is to avoid overwhelming infection.

Now the scary thing is that eating a high fat meal, probably based on any fat which generates chylomicrons, markedly increases you uptake of endotoxin from your gut, which is obviously full of gram negative bacteria. Eating short chain fatty acids or carbohydrate does not have this effect.

OK, so the prediction from this research is that eating a diet which generates chylomicrons will produce all sorts of nasty changes in your body. Hmmmmm, well maybe, but I've not noticed.

Then came a fascinating random paper through my wife's journal club meetings, which are a routine part of her PhD. It's about superinfection with resistant bacteria when broad spectrum antibiotics are used. This is a routine problem for anyone in medicine, especially patients. The concept is very simple, you kill off the susceptible commensal bacteria in the gut and resistant pathogens have no competition, so they have a field day and superinfection causes severe problems for the unlucky patient.

Simple, straightforward and wrong.

It turns out that the immune system, that is the innate immune system (of course), continuously monitors the contents of the gut by looking at endotoxin production. Lots of bacteria mean lots of endotoxin and an active, on-guard innate immune system. Kill off 99% of your gut bacteria and exdotoxin production drops. The innate immune system goes on vacation and clostridium difficile gets in and wipes out your granny.

Simple administration of oral endotoxin to the experimental mice stopped this effect completely.

So yes, it looks like chylomicrons carry endotoxin. Phew. That's better than a clostridium difficile infection!

Reminds me of Uffe Ravnskov's paper on the benefits of LDL cholesterol in gram negative septicaemia. Must dig it out for an airing.

Peter

Fructose and triglycerides

Here's another interesting anti fructose snippet.

Slowly, slowly a tiny step at a time. The strange thing is that these people probably think it's the triglycerides that kill you. Probably their next step is to theorise that if they just had a drug to stop apples raising triglyceride levels you could eat that apple without raising your risk of a heart attack. But what if it's the fructose per se that is the problem and the trigs are just a marker of how much fructose you have eaten? The apple hates you for eating it and it will have its revenge.

Peter

The cholesterol fed rabbit

This video clip reminded me to put up the first few slides from the cholesterol skeptic presentation late last year. Squiggs is cooking scrambled eggs to feed to his toy rabbits, and to himself of course. It's Leonard Cohen in the background.



I began the talk with a quick overview of cholesterol. How it was originally Bad, then it was subdivided in to Good and Bad. Then the Good became good Good and bad Good. And the bad became bad Bad (small dense LDL) and good Bad (large fluffy LDL). Of course not forgetting IDL which can be good or bad depending on when it occurs! And triglycerides were Bad (big trigs) unless, of course, they were Good (small trigs).



But the initial studies simply used total cholesterol to start the ball rolling, a measurement which is now generally considered irrelevant. The ball should have stayed still.

Next was a brief overview of the metabolism of the rabbit



the fact that it is a fibre-vore which runs its metabolism on free fatty acids derived from cellulose fermentation in its hind gut, usually eating Timothy Grass as its sole food.



Timothy grass is 0.6% fat fresh weight and contains no cholesterol. The lipid hypothesis was derived from feeding rabbits up to 5% of their food as chemical cholesterol dissolved in Wessen oil, which is mostly linoleic acid. This even shocked Ancel Keys!



Ultimately the stupidity of transferring this model to the cause of atherosclerosis in humans has to be summed up by Ancel Keys in one of his few moments of lucidity



The final slide in this section was looking at the cholesterol fed rabbit in human terms, including the chap who ate 25 eggs per day for 13 years plus.



Next was the Six Nations Study

Peter

Vitamin D3 again

For UK people looking to measure 25(OH)D3 (and a few other parameters thrown in it seems) Sue sent this address

http://www.biolab.co.uk/vitamins.html

Very reasonable cost but you will need guarenteed next day delivery or a courier, and time the sample appropriately too.

Peter

Vitamin D3 supplements

Just got my 25(OH)D3 result back, 124ng/ml. Bit on the high side so I'll back off from 12,000 iu a day to 9,600 iu for the rest of the winter and maybe do 7,200 iu/d if I get some sun this summer... Roll on

Peter

EDIT: Ionised calcium 1.16mmol/l, normal range 1.12-1.37. No suggestion of hypercalcaemia.

Multiple Sclerosis and Optic Neuritis

This post, like the first on MS, started with the conversation I had over lunch with Prof Ebringer and has been kicked around in my head for a few months afterwards. Here's the next phase.

The immune system is quite complex. Apart from defending us against microbes it appears to be quite important in healing. The formation of antibodies against damaged tissues seems to be quite routine and is probably part of the normal healing process. When those auto antibodies are made against proteins which are not limited to the damaged tissues you can get auto immune diseases in the aftermath of injury. Best documented is pemphigus, where the initial antibodies to skin proteins can be produced in response to damage by anything from UV radiation or thermal burns to surgery or drug adverse reactions. Sometimes the problem goes away with removal of the trigger or after healing of the injury, other times it's there for ever as a self perpetuating, on going, catastrophic problem with auto immune attack on the skin.

Let's talk optic neuritis and multiple sclerosis. Optic neuritis is an inflammatory injury to the optic nerve. Usually it has no obvious cause (think gluten!) but occasionally it comes directly associated with sinusitis. The sinusitis does not have to be caused by acinetobacter, any infection will do, it can even be subclinical.

Treatment, by aggressive surgical and medical management can produce prompt resolution of both the neuritis and sinusitis if a correct diagnosis is made (difficult if the sinus problem is subclinical and an MRI is not available!). The theory linking the two problems seems to be a localised inflammation, plus venous spread of a frightening soup of inflammatory mediators from the sinus past the optic nerve.

The nerve is clearly injured, as reflected by the chunks of lost vision. The injury is not permanent if the sinusitis is successfully treated. The question to me is whether there is enough damage to the optic nerve for the myelin sheathes to be recognised by the immune system as needing antibody production, aka skin burns and auto antibodies to skin. If the damaged nerve does trigger antibody production you are set up with anti-myelin antibodies, which just might have you set up with an on going anti myelin syndrome, call it MS.

About half to three quarters of the people who get idiopathic optic neuritis go on to develop MS. The question to me is whether these are the half or more who had acinetobacter in their sinuses or those who developed auto antibodies to their myelin as a direct result of inflammatory mediator damage. I don't think there is information available which allows us to come to any conclusion about this. It is even possible that the initial priming of the immune system by direct nerve damage from sinusitis can be maintained and promoted by chronic acinetobacter respiratory infection or vice versa... A number of MS patients may be straight gluten toxicity mediated by the innate immune system in the absence of antibodies to anything.

The idea (somewhat abstract) of antibodies to damaged nerves is interesting as it has similarities to immune mediated damage to nerves seen in the various experimental autoimmune encephalomyelitis models used to study MS. These are interesting in their own right and being injected with nerve tissue, especially from other species, appears to be a particularly potent way of generating "MS like" syndromes. They can be another post.

Peter

Multiple Sclerosis and Hydrogen

Thanks to Stephan for getting me re started on this post. Hydrogen matters.

I've been interested in diet and MS for some time. JK has apparently treated a small number of patients and Barry Groves has an interesting section on Second Opinions, mostly discussing a small series of 15 patients treated by Dr Lutz, plus a lady who put her MS in to remission by following the dietary advice in Eat Fat Get Thin.

Lutz is very interesting and cautions against aggressive, sudden onset LC nutrition in this disease as there can be a severe flare. He also mentions this phenomenon in a number of (non MS) sections of Life Without Bread. Being a medic he has the facility to use corticosteroids under these circumstances and did so as needed. There is probably a whole post related to this idea, but I think it holds water.

Anyway, MS appears to be manageable using diet. I'm going to try and look at some of the aspects as to why, though there seem to be several related ways of developing MS, which complicates matters. Intestinal dysbiosis and hydrogen production are probably crucial to development and offer some plausible mechanism for achieveing remission.

As we all know, helicobacter gastritis is facilitated by hydrogen gas produced from carbohydrate fermentation in the colon (or the small intestine if you have adequate dysbiosis). Interestingly helicobacter appears quite happy to colonise both your respiratory system and the calculus on your teeth, presumably given enough hydrogen. The authors of the paper which looked at the role of hydrogen speculated that other infections, particularly of the respiratory tract, might also be facilitated by access to hydrogen.

One other bacterium which appears to be extremely fond of hydrogen is acinetobacter. In its free living guise, just look where you can find it. All you have to do is to give some legumes the equivalent of intestinal dysbiosis by modifying their nitrogen fixing bacteria to "excrete" hydrogen, plant them in a field and there are the acinetobacter, eating it up.

Acinetobacter bacteria are ubiquitous in soil, as commensals on skin/ mucous membranes and as pathogens. The pathogenic species love the respiratory system of critically ill patients and have an initial preference for the sinuses before generalising in to the lungs, blood stream and mortuary.

Respiratory infection, especially sinusitis, has a very long and respectable association with MS. This paper gives the picture:

"MS and chronic sinus infection were also significantly associated in the timing of attacks, in the age at which patients suffered their attacks, and in the seasonal pattern of attacks"

The p value for the association was p<0.0001, quite impressive provided you remember it's an association in a retrospective observational study, not an intervention trial.

I am interested in Prof Ebringer's work on MS and acinetobacter. Prof Ebringer has a systematic technique for seeking out peptides in bacterial proteins which might reasonably be associated with auto immune diseases in humans. Obviously, for MS, you are looking for amino acid sequences in bacterial proteins which resemble a protein in myelin, the one which is targeted for attack by the immune system to give MS. Plus a few other neurological protein targets.

Acinetobacter has such peptide sequences in several rather obscure sounding enzymes. The next question is whether patients with MS have elevated antibodies to acinetobacter bacteria. Yes, they do and they also have elevated antibody counts against synthetic peptides identical to those putative trigger sequences too.

So where does that leave diet? I'm not a great enthusiast for using antibiotics for treating chronic recurrent sinusitis. Drugs are great for acute life threatening problems, or even for acute onset severe sinusitis. Guessing the correct one is part of my job. But bacteria like acinetobacter and its close relative pseudomonas (which shares similar myelin resembling peptides) simply laugh at the pharmaceutical industry's offerings. No, reducing the pathogenicity of these bacteria requires manipulation of their environment.

As an aside on pseudomonas, I was a student in Camden Town just after the IRA bombed the Tower of London in 1974. The many burns patients from this particular episode (which made you quite uncomfortable walking past litter bins in central London) were successfully treated for potentially lethal pseudomonas infections using the vinegar and hair drier technique mentioned above, when all of the antibiotics available at the time were useless. This was cutting edge for our pharmacology lecturers and it certainly taught me something about bacteria.

Back to acinetobacter and respiratory infection. I still get colds. So do my wife and son. LC friends do too. But the chronic persistent gunky nasal discharge, chronic sinusitis or persistent cough (for weeks or even months for some) that used to be a routine sequel to colds are a thing of the past. Respiratory bacteria live in an oxygen rich environment. Hydrogen, as noted by Stephan, Kwasniewski and NASA, is a very high energy molecule in the presence of oxygen. It can power a respiratory infection just as well as it can power an Apollo rocket. No hydrogen means no fuel.

Acinetobacter live everywhere. Having them in your nose is common. We've probably always had them. Converting that balance to a chronic purulent sinus infection is arriving in the modern world.

Getting rid of sinusitis strikes me as one route to removing the most likely trigger factors for MS. Marked reduction of hydrogen production from gut dysbiosis is probably essential to this. That means minimal fibre, minimal fructose, minimal gluten, minimal flatulence. Anything else we can do to normalise our immune function after that will probably help too.

But for someone with MS and a weakness for baked beans, hmmmmmm......

Peter

Saturated fat and the FSA

Well it looks like the doner kebab defamation is just a tiny part of a more concerted attack on saturated fat by the UK Food Standards Agency. After Chris ruined my morning by forwarding this link (thanks Chris! No, seriously, we need to know that stuff like this is happening...) I spent some time browsing the FSA web site. Ugh.

A brief snippet looks like this, on colorectal cancer

"There are thought to be a substantial number of dietary factors, and factors related to the diet, which may modify the risk of colorectal cancer, e.g. diets rich in plant foods are thought to be protective. The mechanisms by which dietary factors can alter the risk, and a clear causal link between diet and the risk of colorectal cancer, are yet to be fully established"

Especially the way they say that there is no "fully established" mechanism or "clear causal link" between such practices as eating plants and colorectal health, there is an assumption being expressed here. Maybe I should email them some of the papers from the WHEL study. Or maybe emigrate. Unfortunately the FSA seems to rule Scotland too, so not much benefit from heading north of the border...

The main up side is that even in the USA it looks to be possible, as Richard shows, to buy good quality food, though it might not be available in every location. I can see us going the same route. Food elitism for the educated. The rest eating what JK describes as slave food.

Peter

Hunting, gathering and starving

I like Ray Mears, or to be more accurate, I enjoyed the TV series he and prof Gordon Hillman made for the Beeb back in 2007. This is probably the one set of programs, other than the Simpsons, that I've watched in the last five years.

Their struggle to find, and then render edible, any sort of bulk carbohydrate in a temperate climate was amusing, especially when they offered the camera crew a taste of one of the less edible concoctions they had produced! The fish and the venison looked good.

The camera crew are very important. Whenever I see advertising for a jungle survival documentary I always think first of the poor camera crews in deepest Borneo or wherever, lugging all their food around as well as their film gear. It must be hard filming someone living off the land while subsisting on baked beans, but then television is a hard calling. Happily Survivorman is self filmed, which limits the suffering of film crews.

The post by Dr Davis had me thinking about evolution and survival, especially these lines:

"The Survivorman show documents the (self-filmed) 7-day adventures of Les Stroud, who is dropped into various remote corners of the world to survive on little but ingenuity and will to live. Starting without food or water, the Survivorman scrapes and scrambles in the wilderness for essentials to survive in habitats as far ranging as the Ecuadorian rainforest to sub-arctic Labrador"

Looking at this sort of TV entertainment (which is probably very good TV, I'd probably enjoy it) as a lead to how humans ate before civilisation strikes me as a bit flawed. There are actually a few places on Earth which are fundamentally uninhabitable, but then no one lives in them. If there is food and an even remotely hospitable environment, we seem to have moved in there long ago, before eventually being wiped out by the forefathers of TV crews.

But we weren't hungry, at least not for most of the time. Population size is controlled by food supply, humans live in tribes of between about 20 and 80 individuals and a tribe will have a territory of a size appropriate to support itself. The members of the tribe will be highly adept at obtaining adequate food supplies from that area. If this is impossible then the tribe would either be smaller or it would be somewhere else. Or dead.

Everyone alive today comes from a very, very long line of successful hunter gatherers. The only reason we are here is because what our distant ancestors did was highly successful. Anyone who's great great great great (X100)th's grandmother died of starvation before having any children is not here today. We are the product of success.

That is tribalism as it has always been. All tribal humans are fully equipped with absolutely everything they need in terms of utensils and knowledge to survive in reasonable comfort where they live. If the comfort is too great, humans will breed to use up the extra food supply. Tight times may be intermittent, but they function to reduce the population slightly and maintain the balance. Tribalism got us here and the phenomenon of a solitary struggle to survive in extreme conditions is a product of Civilisation. The struggle often comes from the ignorance of tribal survival knowledge. Even a group of 100 individuals do not make a tribe. Look what happens when you put over a hundred Royal Navy explorers on to the Arctic ice in 1845 without tribal knowledge or behaviour. Probably with complete disdain for the natives.

This is the unsuccessful Arctic expedition of Sir John Franklin, when all 120+ men perished. The accounts are quite depressing but what is most interesting is that in this extreme, lethal environment where explorers (at the then cutting edge of British naval ability) were starving to death, over 100 native Eskimo were living. Living as they always had, men and women, making babies and looking after toddlers, routine tribal stuff. To the Inuit, fully educated in tribal life of the area, Franklin's expedition died of starvation in a food aisle of Sainsburys. A good speculative account, such as could be made out in the 1930s, comes from Stefansson's "Unsolved Mysteries of the Arctic", cheap on Amazon and far more detailed than anything on Wikepedia, though it lacks some of the modern forensic evidence.

The follow-on from this is the complete lack of respect for the early explorers amongst the Inuit.

The Inuit were there in the Arctic, which was an extreme environment to the Victorians, because there was enough food, shelter and warmth for them to live family lives there. It may not always have been comfortable, but it was successful. They certainly were not struggling to survive. A man alone with a camera is not where they were ever at.

Peter

My favourite source of thought on human evolution is, as always, Daniel Quinn.

Kebab update

Slightly mixed news on the kebab front for UK fans of saturated fat. While a single average doner can give you, if you're a woman, a cracking 346% of you nanny state saturated fat allowance, the down side is that some kebabs contain trans fats. While I'm probably not as phobic about trans fats as some (since reading this table here, where 2.2% of calories from trans fats was associated with significantly less progression of CAD than 1.0%! Discussed here), I'd still prefer not to eat them at all. Of course, with the level of disingenuity in this and similar reports, they could be refering to vaccenic acid and conjugated linoleic acid from ruminal bacteria. Who knows?

A wine glass and a half, nearly two, of fairly saturated animal fat seems to be an excellent base for a meal, although the article describes this as drinking, pardon my quick retch in the corner, that much "cooking oil"!!!!!

Main stream nutrition seems to have it in for kebabs at the moment. There must be something seriously good about that much fat to draw such fire...

This evening's kebab was very good.

Peter