Surwit diet and derivatives

As a counterbalance to the papers documenting the obesogenic effect of PUFA containing diets I'd like to have a brief aside about the Surwit diet. There's a nice list of the ingredients here.

The first thing to say is that it is based around hydrogenated coconut oil. I would guess this is fully hydrogenated coconut oil, though the manufacturers do not specify. To supply a small amount of PUFA some soybean oil is added to give just under 7% of fat as PUFA which, at 60% of calories as fat, translates to 4% of total calories as PUFA. That is low yet the diet is one of the most obesogenic on the market.

There is more to obesity than PUFA (gasp).

The whole drive of the Surwit diet appears to be to supply glucose in a form which will be rapidly absorbed and so allow penetration beyond the liver and in to the systemic circulation. Maltodextrin is used for this. The diet uses a medium chain length polymer of glucose which has a glycaemic index in the same ball park as pure glucose.

Systemic hyperglycaemia is combined with sucrose at 17% of calories to induce pathological insulin resistance and a little extra hyperglycaemia. This is combined with the normal physiological insulin resistance associated with oxidising saturated fats. The need for extremely high levels of insulin to maintain normoglycaemia appears to be adequate to force lipid storage in the face of adipocyte insulin resistance. It certainly works, even with minimal PUFA.

Then I got side tracked in to Surwit's early work. A great paper is this one using F1850 for a publication in 1988:

Diet-Induced Type II Diabetes in C57BL/6J Mice

F1850 is still interesting despite having a bit more linoleic acid (around 7% of calories). This still feels like quite a low dose for a mouse diet. The paper has some great graphs. Let's have a look and ask some questions.

Take two mouse strains (Bl/6J and A/J mice), feed both on sucrose, maltodextrin and modest linoleic acid lard supplying about 7% of calories as PUFA. Both strains get fat, like this:

The bottom two lines are the two strains of mice on standard crapinabag and we can ignore these. Today's quiz is to identify the top two lines based on the fasting blood glucose/insulin data.

Here are the fasting insulin and glucose levels after 24 weeks of exposure to either control or obesogenic diet:

Grey columns represents the crapinabag fed mice, black columns the obesogenic F1850 diet fed mice. It is quite clear that while the A/J mice became modestly insulin resistant it was the Bl/6J mice which became severely insulin resistant, with marked increases in fasting insulin and glucose. On the same diet as the A/J mice.

Now, match the mouse strain to the upper traces on the weight gain graphs. We can ignore the crapinabag fed lower lines. Of the two upper lines one represents a set of mice which is fatter than the other. Are B/J or Bl/6J fattest? From the insulin data...

If you carry the idea in your head that insulin causes obesity you might expect the hyperinsulinaemic Bl6/J mice with a fasting insulin of 150microU/ml to be fattest. If you consider that the mice on sugar become fat because they find the sugary food more "rewarding" (it's the same food, idiot!) you might come to the idea that obesity is caused by overeating and that obesity secondarily causes insulin resistance (no sniggering at the back there). And both are incorrect.

The fattest mice are the A/J mice. They are fattest because they are the most insulin sensitive.

Insulin signalling, not insulin per se, causes fat storage.

The Bl/6 mice, on the same diet as the B/J mice, are more insulin resistant so resist insulin induced weight gain. Significant weight gain still happens because gross hyperinsulinaemia can overcome insulin resistance. But the greater weight gain for the A/J mice is much easier by using less insulin combined with lower insulin resistance.

The A/J mice become "fat but fit" based on glucose/insulin levels. Given long enough they will, undoubtedly, join the Bl/6J mice but they have a longer way to go to become adequately obese to resist insulin. But I have no doubt this will happen on F1850.

I think the difference between the strains is genetic and that Bl/6 based mice generate enough ROS to generate significant insulin resistance at much lower levels of insulin signalling than B/J mice do. If I had to guess at a gene I would go for their truncated supercomplex assembly protein causing failure of supercomplex formation and so allowing electron leakage to molecular oxygen from the ETC at times when no such thing should happen, at least not until the CoQ couple is a great deal more reduced.

But that's just speculation, which is fun.

Humans look more like B/J mice (normal ETC) than Bl/6J mice to me.

Bottom line: Insulin signalling is what makes you fat. Insulin resistance resists this. It's all in the data.

Peter

Addendum. Insulin sensitivity is a Good Thing. But it makes you fat, which is a Bad Thing. Let's rephrase that: Insulin sensitivity is a Good Thing provided you don't use it! Perhaps that concept is worth a post in it's own right.

The miracle of safflower oil (4) Soybean oil is just as good

I picked this paper up from George Henderson via twitter

Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial

which is part of the same study as this one

Effects of Macronutrient Distribution on Weight and Related Cardiometabolic Profile in Healthy Non-Obese Chinese: A 6-month, Randomized Controlled-Feeding Trial

The study is amazing. The researchers provided all of the food to all of the participants for six months. The only fat source was soybean oil. It could almost be a rodent study. This is what the study says:

"The three diets were isocaloric, the primary distinguishing feature being their fat and carbohydrate content (Table 1). By replacing a proportion of energy derived from carbohydrates (white rice and wheat flour, the most consumed carbohydrate sources in China contributing to 70% and 17% total carbohydrate respectively) with fats (soybean oil, the most consumed edible oil in China rich in unsaturated fatty acids)..."

Just a few things to point out: The diets were isocaloric. No one was allowed to select their calorie intake. Blokes got just over 2000kcal/day, women got 1700kcal/day. Some supplementary fruit was allowed, to be recorded as and when eaten.

Here are the baseline diets for each of the intervention groups:

Here is what the intervention diets looked like:

Particularly note the exact match of calories normally eaten at baseline compared with that supplied by the study intervention, which was utterly accurately measured out in the study kitchen.

What happened to the weights during the intervention? This did:

The yellow line is 24% PUFA, red is 18% PUFA and blue is 11% PUFA, all by energy intake.

The first thing to say is that all participants lost weight. I guess that has something deep to say about the accuracy of three day dietary records!

However the weight loss was far from uniform and was clearly inversely related to the level of PUFA in the diet. Less PUFA, greater weight loss, 2kg in eight weeks for the lowest PUFA group. This cannot be explained by reduced food intake because all food calories were provided, in exact amounts, by the study kitchens. Diets were isocaloric...

Protons would suggest that the higher the PUFA content the more dietary fat was "lost" in to adipocytes then not subsequently released. From the cico-tard point of view just over a kilo of fat was "not released" from adipocytes over eight weeks of weight loss in the high PUFA vs the low PUFA group. That's 1000g over 56 days or just under 20g/day. This would have to be countered by a decrease in metabolic rate, in NEAT or specific activity. Or more cheating, recorded or not recorded. The study authors assure us there was no cheating.

After eight to 12 weeks all subjects started to regain weight. The regain slope suggests about a kilo per year on a rigidly fixed calorie, weight reducing food intake.

These people were 23 years old and weighed 60kg. If they stuck with this diet over 30 years they might end up at 90kg. Of course this wouldn't happen if they really stuck with the diet. As weight gain tried to continued on a fixed calorie intake, hunger would increase.

You cannot argue with hunger for 30 years. The subjects would break the diet and eat more. This manifest lack of "willpower" or gross "gluttony" would take the blame for the increased weight gain, which would be blamed on the increased calorie intake.

But the weight regain was already there on a rigidly fixed calorie intake. A calorie intake which gave eight weeks of initial weight loss. This still gave a progressive weight gain with no declared increase in caloric intake.

The beauty of PUFA and the Protons concept.

Peter

NB It is difficult to emphasise how good this study is. Just ignore anything the authors have to say.

The miracle of safflower oil (3)

TLDR: PUFA in a mixed diet are obesogenic. PUFA under hypoinsulinaemic conditions are not. I doubt they get a free pass long term.



There have been some interesting snippets on Twitter recently, triggered by Diet Doctor's discussion about vegetable oils here. Perhaps the most controversial quote is this one:

"Disclaimer: Vegetable oils are routinely recommended as “heart healthy.” There is high-quality evidence demonstrating that replacing saturated fat with vegetable oils reduces LDL cholesterol levels. But at this point, there is inconsistent evidence whether this translates into fewer heart events or lower rates of cardiovascular mortality".

This is absolutely incorrect for people with pre existing cardiovascular disease as it was found, in a randomised control trial using safflower oil, that increasing vegetable oil for bulk calories will increase all cause mortality (p = 0.05), cardiovascular disease mortality (p = 0.04) and coronary heart disease mortality (p = 0.04). Mortality is an utterly hard end point and particularly the all cause mortality is an end point which cannot be argued with.

Let's rephrase that: in the context of a mixed diet in people with established heart disease vegetable oil (from safflower seeds) is going to increase you risk of death, especially from cardiovascular disease.

The main issue is to ask whether this still applies under low carbohydrate eating conditions. Given the role of insulin in CVD this is far from certain. But context will be crucial here and who would like to be the guinea pig?

The interesting twitter conversation goes like this:

Dr Westman: "In 20 yrs of clinical research and practice using LCHF/keto, I’ve never even mentioned reducing omega 6s, and it works wonderfully. Just cutting carbs gets the job done!"

Tucker: "I disagree, but @drericwestman is an excellent physician who does great work. This is more about determining ultimate causation so we can address people who can't just go low-carb, which is most of the planet".

I think both people are correct. I came to LC because it works. Over decades I've read studies where it works pretty much invariably on a group basis and studies from the mainstream usually advise progressively increasing carbs if they want to knock low carb and secure future funding. You have to pay the mortgage.

I am perfectly willing to accept that consuming carbohydrate in a rapidly absorbable form will overwhelm the liver's ability to protect the systemic circulation from hyperglycaemia so will require systemic hyperinsulinaemia to control that systemic hyperglycaemia. In particular hyperinsulinaemia comes with its attendant problems (ie most of medicine) but obesity only occurs when hyperinsulaemia is marked enough to overcome insulin-induced insulin resistance. I have no doubt this can occur without PUFA but I think it is massively easier in the presence of PUFA, which delay normal insulin-induced insulin resistance in the immediate post prandial period.

The role of polyunsaturated fatty acids is to stop adipocytes developing insulin resistance by limiting ROS generation. Combining hyperinsulinaemia with hypersensitive somatic cells is a recipe for maximising lipid storage in adipocytes and simultaneous packing lipid in to muscles, pancreas and anywhere else you care to imagine that sprouts an insulin receptor (most brain cells excepted).

Eating a low carbohydrate diet side-steps the problem by reducing absolute levels of systemic insulin. Down a set of unrelated rabbit holes I'm looking at what might control hunger under LC eating and PUFA may have some influence on this, but it is clearly a small effect when compared to the same dose of PUFA combined with an insulogenic diet.

Ultimately at low levels of insulin it doesn't matter how well or badly adipocytes respond to/resist insulin. There is so little insulin about that FFAs and ketones are able supply the body's energy needs, given some excess fat (especially visceral fat) available to be utilised.

Back to long term speculation: Do PUFA matter for non-insulin reasons on a low carb diet? Recall that López-Domínguez et al used a low calorie semi-starvation model (which is a partial mimic of low carb eating) to look at longevity in rodents (post is here). It certainly matters under their study conditions but the effect is small enough that I doubt it would show in any way for someone at 40 years of age under a year or two's exposure to a high PUFA but low carbohydrate diet. For those of us in this for the long haul it's much easier not to be the test case and PUFA avoidance seems prudent to me.

And I am undoubtedly still a low carb eater.

Peter

The miracle of safflower oil (2)

Just a brief mention of this one:

Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis

merely because they used the same miraculous safflower oil as featured in the last post. This was a secondary prevention trial and increased safflower oil derived linoleic acid to around 15% of calories, again with no attempt to remove the ubiquitous industrial trans fatty acids from the control diet.

Here is the all cause mortality over 5 years

It's interesting that the increased death rate kicked in almost immediately, ie there is a case to be made for direct toxicity rather than the rather abstract concept of accelerated ageing that I've speculated about previously.

Ramsden published these recovered data in 2013. I guess seven years might be a little too soon for it to have filtered down to the World Health Organisation or Public Health England.

Talk about blood on their hands.

Peter

The miracle of safflower oil

TLDR: Increasing insulin sensitivity makes you fat.

This study is a bit of a mess because there are no control groups. People either got the safflower intervention or the conjugated linoleic acid intervention, then they were crossed over:

Comparison of dietary conjugated linoleic acid with safflower oil on body composition in obese postmenopausal women with type 2 diabetes mellitus

I'm going to ignore all of the CLA/post CLA data and look at the subjects who got just safflower oil, a total of eight capsules per day, two with each meal plus two at bedtime, eight grams a day of the oil for the first 16 weeks of the study. The safflower oil was 78% linoleic acid, regularly checked by gas chromatography.

Looking at Table 3 there was no change in total fat mass (and subjects didn't gain any weight on the scales) by DEXA scan while there was a loss of 1.2kg of "truncal" adipose tissue. With a PUFA supplement. It appears that DEXA scanning cannot differentiate between visceral and subcutaneous fat in the trunk area. The authors can't quite claim that there was selective loss of visceral fat but I think it is very likely that this did happen.

Throw in a fall in fasting glucose and a downward trend in fasting insulin levels coupled with a rise in adiponectin, some muscle gain and well, that's pretty impressive. You can, absolutely, see why people might have the idea that PUFA could be very positive for metabolic health.


How might one view this from a Protons perspective, other than reaching for a bottle of safflower oil?

I think the first thing to consider is the (probable) loss of visceral fat. Visceral fat, in my opinion, is utterly harmless. It contains the most insulin sensitive adipocytes in the body. If you are chronically hyperinsulinaemic, especially overnight, your insulin may never drop low enough to release any significant lipid from your visceral fat. So visceral fat is a surrogate for nocturnal hyperinsulinaemia, which is what is actually bad for you.

We have values for 10h fasting insulin; at enrolment it was 19.9microU/ml and this dropped to 18.2microU/ml over the first 16 weeks of the study. I would not expect 19.9microU/ml to maintain visceral fat and 18.2microU/ml to melt it away. I think it is much more likely that the gross hyperinsulinaemia induced by the sort of evening meal recommended by the ADA for diabetic people might well have resolved faster with safflower oil supplementation than it did without safflower oil, ie the duration of the period of gross hyperinsulinaemia through the night was reduced. Fasting levels were unchanged but the time spent above this ought to have been reduced.

We just have to revisit the Spanish study to see why:














This graph is over eight hours, 10 hours would be similar. These are healthy volunteers, the hyperinsulinaemia would be worse in DMT2 patients eating a high carbohydrate meal. Black squares are butter, white triangles are a high PUFA seed oil. The higher the PUFA content of the meal, the faster insulin level drops. Adding PUFA a mixed meal should allow insulin to drop faster and sooner than saturated fats. This happens because PUFA fail to generate the ROS needed to maintain the physiological insulin resistance which ought to occur post prandially to limit calorie ingress in to cells, adipocytes included. This leaves glucose and fatty acids available to signal satiety to the brain. Also noted in the Spanish study was that PUFA induced more rapid clearance of chylomicrons and more rapid drop in FFAs compared to saturated fats. As I wondered at the time, where do the FFAs and chylomicrons go to?

They go in to adipocytes, because the adipocytes cannot say "no" if PUFA generate too little ROS.

So this drug (safflower oil) allows increased insulin sensitivity (reminiscent of the "glitazones") or, rather, it fails to generate the ROS needed to limit the over expansion of adipocytes, which shows as increased insulin sensitivity during peak insulin exposure. This increased insulin sensitivity puts calories in to adipocytes rapidly so reduces the need for sustained hyperinsulinaemia. All adipocytes gain fat, but the faster fall in insulin allows an increase in the time window where visceral fat can actually release at least some FFAs to the systemic circulation via the portal vein and liver. Visceral fat shrinks, non-visceral fat expands.

The "benefit" of reducing visceral fat in this way during fasting is paid for by increasing the non-visceral fat depots in the immediate post prandial period. The extra fat in non-visceral adipose tissue will come primarily from the diet and the lost fat from visceral adipocytes will be used to provide fasting calories. In this particular study, the amount gained by non-visceral adipocytes was roughly equal to that lost by visceral adipocytes, it's probably random chance that the numbers balanced. And DEXA seems a pretty crude technology to use to work in small numbers of grams of adipose tissue, just looking at the non-balancing cited changes in fat and lean tissue mass in the results.

These processes can continue until non-visceral fat mass eventually become high enough that the loss of FFAs due to adipocyte distension over rides the insulin sensitising effect of the safflower oil. At this point overall insulin exposure will increase and visceral fat will return, on top of a higher mass of non-visceral adipose tissue. It will take longer than 16 weeks.

If you are an obese diabetic taking part in a study like this you should see a prompt but transient improvement in insulin sensitivity. This enhanced sensitivity should allow more non-visceral fat gain until you convert to being a somewhat more obese diabetic. It nicely illustrates that extra PUFA convert you from being established "obese" to being "pre-more-obese". Time is all that is needed to convert you from being "pre-more-obese" to simply"more-obese".

But your lab numbers will improve transiently in the first part of the intervention.

Peter

Double Bond Index and longevity in humans

Preamble: I've had this post written for some time (there are a fair few in this category) but this tweet from the World Health Organisation has prompted me to hit the publish button. In particular this piece of advice begs the question of incompetence vs malicious intent (I doubt the latter):

Here's the post:

I thought I would revisit the idea of trans fatty acids because the late Fred Kummerow got an honourable mention on twitter recently. He is largely responsible for the removal of industrial trans fatty acids from the food chain. No one would argue that that was not a Good Thing.

Back in the 1970s a study was completed which applied a diet from which saturated fats were largely removed and linoleic acid, mostly from corn oil, was increased to about 13% of calories. In a "control" diet saturated fats were as unchanged as practical and linoleic acid limited to just under 5% of calories. That should be a pretty good test of the miraculous benefits of dietary PUFA for blood cholesterol lowering.

However the "control" diet just happened to be specifically increased in industrial trans fatty acids from commercial margarine (1960s style USA margarine), though no one knows by how much, ie there was no genuine "control" diet.

This is what the diets looked like

Cholesterol lowering diet:

"Liquid corn oil was used in place of the usual hospital cooking fats (including hydrogenated oils) and was also added to numerous food items (for example, salad dressings, filled beef (lean ground beef with added oil), filled milk, and filled cheeses). Soft corn oil polyunsaturated margarine was used in place of butter. This intervention produced a mean reduction in dietary saturated fat by about 50% (from 18.5% to 9.2% of calories) and increased linoleic acid intake by more than 280% (from about 3.4% to 13.2% of calories)".

"Control" diet:

"It was designed to appear similar to the experimental diet. Notably, free surplus USDA food commodities including common margarines and shortenings were key components of the control diet, making the daily per participant allocation from the state of Minnesota adequate to cover the full costs. As common margarines and shortenings of this period were rich sources of industrially produced trans fatty acids, the control diet contained substantial quantities of trans fat. Compared with the pre-randomization hospital diet, the control diet did not change saturated fat intake but did substantially increase linoleic acid intake (by about 38%, from 3.4% to 4.7% of calories)".

You have to wonder about the inclusion of trans fats in the control diet. Did Ancel Keys (co-principal non-author) realise, even as long ago as the mid 1960s, that trans fats were bad? A little stacking of the deck has never been been considered an issue when it might help support the lipid hypothesis.

The experiment, designed to confirm the benefits of PUFA, failed completely. There was zero benefit from cholesterol lowering using dietary linoleic acid. Keys never published the results, hence my use of the term "co-principal non-author" because non published study results cannot have any authors. Happily enough data were excavated by Ramsden et al 40 years later to be published in 2016 as

Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73)

There was, overall, no effect on total mortality when comparing the two interventions. To rephrase that: Increasing dietary linoleic acid was no worse than increasing trans fats, overall.

OK. So we could stop there with nothing more insightful than an observation of the moral and scientific bankruptcy of the architects of the lipid hypothesis. Nothing new there.




But what we actually have here is a study comparing two diets, one with a marked increase in the double bond index (DBI) of the lipids vs one with a modest increase in DBI, if we ignore the problems of trans fats.

We have something resembling the CRON mouse study in which lard as the lipid source gave a greater longevity benefit compared to fish oil or soya oil. We can view the present study as an intervention which altered mitochondrial membrane lipid composition in a direction of enhanced ageing based on increased DBI of those membrane lipids. But this time in humans, and with no calorie restriction.

Rather than looking at specific diseases we can ask whether increasing the DBI of your mitochondrial lipids might simply make you biologically older than your chronological age. This should show in the all cause mortality data, irrespective of the cause of death (ignoring "One flew over the cuckoo's nest" scenarios, even though this was a mental hospital study). However this would be hard to isolate in younger people because they are far enough, chronologically, away from death that ageing them by 10 years (a totally fictitious value, merely used for illustrative purposes) wouldn't show up much in all cause mortality. Assuming the risk of death at 40 years of age is similar to that at 50 years of age, nothing will show.

But, if you are 65 years of age and eating 13% of your calories as corn oil derived polyunsaturated fats makes you behave biologically as if you are 75 years of age, this just might show as increased all cause mortality.

Ramsden provides us with these graphs. In people under 65 years of age nothing shows:

but in people over 65 years of age there is visibly increased all cause mortality in the corn oil subjects:

Because the raw data for these graphs could not be recovered it is impossible to perform any sort of statistical analysis but it looks to me like there might be some indication that basing your diet around corn oil PUFA might be worse than eating trans fats, late in life. Given the raw data I suspect it might be possible to calculate how much linoleic acid might shorten your lifespan and by implication I would expect it might also shorten your healthspan, which could actually be worse.

Trans fats come out unexpectedly well. You have to wonder how much more benefit removing linoleic acid might provide, especially if you are an elderly person trying to avoid ARDS in the ITU.

Peter

ARDS isoprostanes and isofurans

This study from 2012 uses a model and it's based on mice. No one, ever, develops ARDS by inhaling reagent grade lipopolysaccharide following an intra tracheal injection of said LPS. So some caution.

Low levels of tissue factor lead to alveolar hemorrhage, potentiating murine acute lung injury and oxidative stress

I was interested, not because of the tissue factor knockout, but in the control group because I wanted quantification of how much haemorrhage occurred in to the alveoli during the progression of ARDS. I was modestly interested in the concept that pulmonary haemorrhage might reduce systemic haemoglobin value, elevate bilirubin, elevate ferritin and induce oxidative stress due to free haemoglobin or its derivatives. It can do some of these things but what caught my eye was the section on inflammatory markers within the small "human" arm of the study.  This is what they found in real people with real ARDS:

"Patients with diffuse alveolar hemorrhage had progressively increasing BAL isoprostanes and isofurans as their sequential BAL aliquots become more bloody. These findings suggest that liberation of free hemoglobin into the airspace and intraalveolar lipid peroxidation may be important mechanisms of clinical acute lung injury".

I would just comment that while both isoprostanes and isofurans measured in the study are arachidonic acid non-enzymic derived peroxidation products I can see no reason why the toxic derivatives of linoleic acid peroxidation would not also be formed, though these weren't measured in the study.

This would fit well with the likelihood of who is most likely to develop ARDS being predicted by the proportion of polyunsaturated fatty acids in their plasma free fatty acid pool on admission to the ITU.

The role in ARDS of pulmonary haemorrhage, intra-alveolar red cell lysis, free haemoglobin and severe oxidative stress in the airspaces is fascinating and is likely to be a routine feature of all types of ARDS. I got here by trying to decide whether the widely discussed concept that SARS-CoV-2 might be doing something special based on viral protein modelling suggesting the displacement of the Fe atoms from haemoglobin could be causal of whole body damage via systemic hypoxia. Looking at the clinical data coming out of Wuhan and what we have known about ARDS for decades makes me doubtful that we need the "iron hypothesis". I'd not say that it is incorrect, just that an awful lot of the clinical data fit with a severe viral infection induced ARDS including pulmonary haemorrhage in patients loaded with polyunsaturated fatty acids.

Peter



I wrote this post some time ago and felt it wasn't really interesting enough to put up, but the iron/haemoglobin idea keeps resurfacing. Loss of Fe from Hb will undoubtedly impair oxygen delivery but it would not cause arterial oxygen desaturation without concomitant lung dysfunction. With normal lung function whatever undamaged haemoglobin remains would saturate perfectly well. A pulse oximeter would still render a reading of 100% saturated even if little functional haemoglobin remained and tissue oxygen delivery was very low, assuming the colour of the haemoglobin derivatives did not interfere with pulse oximeter function. This is the situation in "normal" profound anaemia. In one of the Wuhan reports clinical anaemia on presentation was undoubtedly associated with decreased survival (though this was not related to mean haemoglobin levels) but equally so were decreased platelet count and decreased albumin levels. These would be compatible with serious problems from multiple tissue haemorrhage, lungs included, as part of the advanced stages of SIRS (systemic inflammatory response syndrome) where DIC (disseminated intravascular coagulation, better known as Death Is Coming) becomes one of the terminal features.

The discussion of mechanical ventilation techniques in causing/avoiding pressure injury to the lungs is almost as old as the eternal discussion of colloid vs crystalloid for volume resuscitation. Personally I prefer crystalloids and would favour IPPV techniques which avoid barotrauma to the lungs if at all possible. But that's just me.

Look after your lysosomes: Hydroxychloroquine

This fascinating:

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

Forty two patients were enrolled. Sixteen were not given or refused hydroxychloroquine and none of these were admitted to the ITU, none walked out of the hospital and none were nauseated enough to withdraw from the trial.

Of the 26 patients given hydroxychloroquine three were subsequently excluded from the study because they were admitted to the ITU. Oops. One died (not one of those admitted to the ITU). One walked out of the hospital and never came back. Another was too nauseated on the drug to continue in the study.

Exclude these six patients and in the remaining 20 patients hydroxychloroquine was reported as successful at clearing the virus on nasopharyngeal swabbing.

You have to wonder if the poor patient who actually died while taking hydroxychloroquine ended up with high pH lysosomes which leaked enough cysteine to extract the FeS clusters from the nearby complex I FeS chains. Or simply died of pneumonia before he/she could be admitted to the ITU. We'll never know. I hope the patients "lost" in to the ITU made a full recovery.

Perhaps the patients who accepted hydroxychloroquine were simply iller in the first place and were so more willing to accept an experimental drug. I do hope so but I feel that the initial data on hydroxychloroquine are not looking too promising.

Peter

Edit: On the plus side there might be an effect if given early. However only time and trials will tell if there really is an effect or whether Turkey happens to have done several other things correctly in addition to using hydroxychloroquine. At least they are not reporting toxicity. End edit.

Coronavirus is possibly everywhere

This tweet

https://twitter.com/Yascha_Mounk/status/1246240181440540672

links to this news report

https://www.lastampa.it/topnews/primo-piano/2020/04/02/news/coronavirus-castiglione-d-adda-e-un-caso-di-studio-il-70-dei-donatori-di-sangue-e-positivo-1.38666481

which should be headline news everywhere.

In Lombardy 40 out of 60 blood donations from healthy donors with no history of coronavirus illness are seropositive. They have been exposed, infected but were never ill.

In comments to a pervious post I suggested that the best advice re coronavirus was a) try not to be elderly and b) try not to be diabetic.

Obviously assessment a) was incorrect.

Being elderly is probably only a problem if you drop in to category b) as well. ie age is a surrogate for risk of metabolic syndrome or as Kraft would have described it "diabetes in-situ". There is a simple solution to diabetes in-situ.

Testing of UK blood donations, if it duplicates Italy, should allow some return to normality with continued or increased protection for those most at risk while we get their metabolic syndrome under control. That should take a few weeks of LC eating and might have to be maintained long term. Damn, bacon and eggs for breakfast every day and steak with broccoli and 'shrooms for supper. Cheese and olives for lunch if you're hungry. Sounds awful I know but sacrifices will have to be made.

Peter