I was a little cautious about the efficacy vs toxicity of chloroquine and its derivatives in my last post.
George Henderson just retweeted this snippet;
https://twitter.com/UnitedRda/status/1244299325963829248
Sadly the narrow line between the degree of raising lysosomal pH to blunt viral replication and that which might release sufficient cysteine to strip the FeS clusters out from complex I can be crossed quite easily, so it appears.
Worryingly Dr Barman appears to have been one of those people with some degree of metabolic syndrome and who might have been someone most likely to benefit from prophylaxis against coronavirus replication.
My own observation during my very rare trips to our local hospital is that medical professionals are far from immune to metabolic syndrome. Couple that with extreme stress, high viral load exposure, severe sleep deprivation and the sort of food/snacks available in hospitals and you have to worry for the health of these people.
None of them want to have metabolic syndrome, a problem which is built in to our public health guidelines. These people are laying their lives on the line to support the lipid hypothesis. Most of their patients are in hospital secondary to the lipid hypothesis. Those developing ARDS in the ITU do so in a large part as a result of the lipid hypothesis.
Just my rather sad view from the sidelines.
Peter
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"Meanwhile, Diederik Gommers, chairman of the Dutch intensive care association, told television talk show Jinek on Friday evening that 66% to 80% of corona patients on intensive care wards that he had seen are overweight. The reason has not yet been investigated, but Gommers said it could be linked to the prevalence of diabetes among obese people, which would make them more vulnerable to the virus. In addition, the extra weight can also make breathing more difficult, he said.
"A specialist on the programme gave a similar picture. ‘Almost all the patients on an IC ward are overweight,’ Peter van der Voort of Groningen University’s teaching hospital said. ‘We don’t know why, but it is very noticeable.’"
"Coronavirus death toll rises, obese corona patients dominate in intensive care" : https://www.dutchnews.nl/news/2020/03/coronavirus-death-toll-rises-obese-corona-patients-dominate-in-intensive-care/
https://www.youtube.com/watch?v=IKOGwg4qHNU
PKD diet and infection.
Cavenewt, the institute monitoring numbers, RIVM, says only 15% of the hospitalized people have diagnosed diabetes.
30% have hypertension. 65% is male. 80% is 70 years and older.
These numbers are roughly the same for the people dying.
They put out statistics every day. https://www.rivm.nl/sites/default/files/2020-03/Epidemiologische%20situatie%20COVID-19%2030%20maart%202020.pdf
Correction: 80% of the deceased is 75 years old or older.
Younger people are in hospital but are not dead. No numbers of recovery are recorded, alas.
Also male is 63,5 percent, not 65.
Tabel 5 is about underlying conditions.
Also I am not Unknown, my name is Anna.
Cave, and the non obese might well be "skinny-fat"...
Kajus, didn't realise that fructose could block the hydroxylation of fit D, interesting.
Peter
That will be vit D not fit D!
Anna, yes, it seems like not being elderly and not being diabetic might be the best plan. Happily everyone has the option to not be DMT2, or at least to side step it if they have stockpiled butter rather than pasta. As for being elderly, that is probably a surrogate for DMT2 in-situ.
Peter
Yes - time to stop the mindless killing of critically ill patients. https://nutritionj.biomedcentral.com/articles/10.1186/s12937-015-0100-6
And I'd say from their baseline total cholesterol that they have all been statinated.
That's a good start! Can you make an emulsion of beef dripping which stays liquid at room temperature?
Peter
Good stuff Cathy! We have played with a lot of different span/tween surfactant/emulsifiers over the years. There might be a good biocompatible one out there. Have to go through my inventory and see what we have on hand.
Someone could design an infusion pump that warmed the dripping or coconut mixture on the way in. Why not?? We could all get together and design a healthy alternative. I don't get it; there are numerous studies showing better outcomes when patients with ARDS have VLCPUFA with a ratio of 2:1 and yet they continue to pump omega 6s in as vile soybean oil. In a current climate of panic and handflapping why has nobody (esp the whipemintopanic epididymologists) had the bright idea of ditching the icky Intralipid and giving patients something less harmful?
And thank you to whoever put the link to the paper suggesting melatonin might be protective with OVID-19. Here is more direct evidence for that. https://www.ncbi.nlm.nih.gov/pubmed/24330221 shame no full text.
Peter, you mentioned mct versions. A butyrate version perhaps? Any lower melting point sfa, more easily emulsified? I guess so. Hell, I'd take IV butterfat, pour it in.
Tell 'em you have a nut or soy allergy perhaps, if you are still verbal enough and unfortunate enough to be in that situation. This is not far from the experience of one of my co-workers only last week who went in for an appendectomy in the middle of all this chaos. She had an anaphylactic reaction to something during the anaesthetic procedure and had to be rescuscitated. She was at work again yesterday!!!
That was me. I'm nobody. Lol!
That's a great idea on the soy allergy idea!
People died in flu epidemics much before the lipid hypothesis was even thought of.
Though I have heard that widespread smoking habit might have been a significant factor then.
Gyan: "Though I have heard that widespread smoking habit might have been a significant factor then. "
As it is now.
And in 1918 mortality was aided by the 20g dose of aspirin that was sometimes prescribed.
Justin, obviously there are a whole load of trials, rct needing doing on anything you stick into sick people involuntarily but I think that if ffa forms of the appropriate lipids could be stabilised and solubilised as opposed to the heavier triglycerides it might be thin enough at room temperature. FFA carried in albumin-like proteins maybe?
Palm oil seems to a have a reasonable lipid profile. There are environmental concerns with some sources of p.o. but also other, ethical sources.
A quick look round pubmed suggests that MCT oils +/- fish oils have all been available, though I've no idea what is commercially marketed nowadays. A recent meta analysis using GRADE suggest the evidence base is of "low" or "very low" quality. Much like enteral nutrition, as in the Food Pyramid, I guess!
Peter
Gyan,
Yes, viruses may have similar basic requirements but they clearly vary in both how good they are at getting their needs fulfilled and in which receptor they happen to use to get in to which cell...
Peter
This presentation does well at showing all the evidence to "date" - unfortunately it is from 2012. I know things filter slowly in medicine but really?? I know how unbelievably expensive TPN is so subbing MCT oil for soybean should not be that big an ask. https://www.bapen.org.uk/members/pdfs/conf_presentations/2012/14.00-14.30-Calder.pdf
@Passthecream - while palm oil may be environmentally a no-no, the amount that would go into TPN would be negligible (from a world perspective) for that purpose surely compared to other uses?
And while I am here among intelligent company and gone half mad with being essentially under house arrest; if you think about the epidemiology of this virus - it does not make sense. In the Spanish flu outbreak it was thought that younger people died because(ASA aside but a massive confounder given that ASA and phenacetin were the only widely available analgesics at the time) they had a "more robust immune response" to the disease. With Covid-19 it seems the same - the body's response to the virus is what causes death and AFAIK no direct mechanism of COVID-19 = death has been elucidated. And yet our young have been largely unscathed and the older population are the hardest hit. So surely this points to a massive modifying factor? They have talked about ACE inhibitors (ACE inhibition upregulates ACE receptors and blah blah which explains virus entry into the body) but does not explain the cytokine storm = ARDS = death. ACE inhibitors are old hat now in lots of cardiology circles - so ARBs perhaps? My largely hypothetical opinion is that there is an underlying and unifying factor (apart from the FFA stuff already discussed). The most common comorbidities are CVD, hypertension and diabetes (not stratified for type 1 vs type 2 but suspect the latter. To me the most likely candidates are statins given that all these conditions require primary statination regardless of other variables. And just by the by - statin use massively increased in Italy over the last decade, plus they also follow the long outdated ASA for primary CVD AE prevention - and along with terrible lipid profiles we have found what the "perfect storm" looks like. God help us (and no I am not religious) and please forgive any typos - I am blind as a bat and there does not appear to be a spellcheck on blogspot.
@Cathy in Manchester UK thanks for various links. That is an interesting suggestion. Could be associational though since statins are heavily pushed ( peddled) upon diagnosis of 'metabolic syndrome' or any of its sequelae. Nothing says metabolic syndrome to me currently quite as much as high consumption of polyunsaturated vegetable oils does. That seems to be the biggest secret evil of the last 100 years. The young may not have had time for it to build up in their adipocytes etc to really harmful levels. Met-syn is not so common in tge young either.
Oh to die for, being an old overweight pre-diabetic smoker taking ARBs, statins and a heart healthy pufa supplemented diet! </sarcasm
Cathy what's your take on the association with declining melatonin production relative to age and an increased risk of complications with infection of Covid-19? Also, I appreciate you showing up and adding to the already interesting dialogue!
Passthecream I agree that a lot of work would be needed to allow this as treatment modality. B
I had a long post written up a while back on the determining the melting points of different fat compositions and it never posted and I lost it. I will try to make some time to share my experience/insight on this when I can. In short you can or the composition in a glass capillary that is submerged in water. You would then observe the temperature in which it becomes transparent. We did this for a lot of different compositions, like cocoanut oil, shae butter, cocoa butter and things added to those. I also dug up some of the dsc curves on them too. I also found an awesome paper outlining the method for quantifying the fatty acid profile of eggs using an old HP5890 gc like I have at work
I'll post it up when I have a chance.
I don't understand why having a robust immune response should be detrimental to the point of actually being fatal. That idea seems very dubious.
Gyan just think about hayfever, Herxheimer reactions, then anaphylaxis.
Complicated doesn't even begin to describe it.
"That's a good start! Can you make an emulsion of beef dripping which stays liquid at room temperature?"
That is laughably easy, why would you think it would be harder than producing a stable emulsion of omega 6?
A bitumen emulsion of over 80% weight solids(usually 84%) can be very thick at room temperature but fairly low viscosity at > 40 C. A 60% bitumen emulsion is basically like water at room temperature, mean particle diameter around two micron for both. How high solids do you need? The bitumen is usually at about 130 C when introduced to the water soap solution at about 60 C in a colloid mill with a combined temp of just under 100 C.
Granted that is normally using a alykl polyamine salt of HCl as the emulsifying agent but low solids emulsions are usually really easy.
Justin until I read the paper in that link I had absolutley no idea about the possible melatonin link. It never occurred to me as I am not clever enough. Having gone through more literature on the stuff it seems a miracle substance. A bit like back cumin oil is supposed to be "a cure for everything except death" (Prophet Muhammed). It helps with aging, osteoporosis, inflammation, glucose homeostatis and many other things. Never mind icky statins; this stuff really should be added to the water supply. I have ordered some already.
Johnnyv can you please come up with a formulation for mayonnaise made with butter? Pretty please?
Passthecream,
Having a robust immune system makes one liable to cytokine storm--how confident can we be in this assertion?
Cathy in Manchester UK: "can you please come up with a formulation for mayonnaise made with butter?"
That's basically hollandaise sauce, only with whole eggs instead of yolks. I have made mayonnaise with various combinations of coconut oil, bacon grease, and olive oil. You just warm up the fat ingredients enough to barely melt them and proceed as with regular mayo. If there's a lot of coconut oil in it, after the finished product is refrigerated you might need to let it warm up to room temperature before using.
It helps a lot if you're not expecting it to taste exactly like commercial mayonnaise.
Adiponectin? This is interesting. https://www.sciencedaily.com/releases/2015/06/150612091544.htm
While we have turned to swapping recipes, I'd like to try to make high stearic acid butter. Has anyone figured out a source of food grade in Europe?
Most of the stuff offered is for candle making, and wouldn't want to take chances.
Then there is something by Naissance 505 in the UK.https://naissance.com/products/stearic-acid
It is cosmetic grade. Is it safe to eat?
It also says it is extracted from palm oil, but palm oil only contains about 2% stearic acid. I can imagine it is leftover residue after destillation. 370°C boiling point vs. 360°C for oleic should be doable but I wonder if that is efficient and yields a pure product.
Seems much more straightforward to hydrogenate oleic acid. There is a fat called Palmin that has been around for ages in Germany. It is purified and fully hydrogenated coconut oil. When it was tested in Ökotest magazine about 10 years ago, it got very good results (no residual chemicals, no trans fats). It just doesn't have long enough chains for my purpose...
Cathy, from my point of view adding omega 6 PUFA makes adipocytes insulin sensitive. Adiponectin will be high while ever adipocytes consider themselves to be too small. This generates hunger. Hunger fills the adipocytes. Once full enough adiponecting will no longer be produced in the same amounts and systemic insulin resistance will occur (whether triggered by low adiponectin or simply by elevated FFAs from un suppressible basal lipolysis). Palmitoleic acid carries a similar signal. So, does the low adiponectin cause adhesion failure or does elevated PUFA cause adhesion failure (and eventually subsequent low adiponectin once obesity is established), especially when exposed to macrophage derived ROS?
Peter
A generous French doctor has kindly compiled a database of drugs known to induce lung toxicity. The list that comes up for ARDS is very lengthy so I will list the more commonly used agents: Fluoxetine, HAART, hydrochlorothiazide, hydrocodone, possibly all the MABs are listed, mTOR inhibitors, methotrexate and... STATINS.
https://www.pneumotox.com/search/results/5e85fd24878cb
I have made some all butter mayo - freshly made was delicious but it remains to be seen how hard it goes in the fridge. I am happy to share the recipe and technique (no tedious drop by drop nonsense) after sampling with my wild caught salmon tonight.
Gyan,
Owning a box of matches is really useful for lighting a fire when you are cold. Lighting a fire in a woodyard using tinder dry wood to make your fireplace might convert your match from useful to lethal? Just a thought.
Peter
Peter the adiponectin angle did not pan out in human observational studies. I think you are right and adiponectin reduction follows obesity rather that causing. Chicken and egg again.
@cavenewt I have also experimented with coconut and butter before and was "cutting" with 30% macademia oil which meant it did not have to come to room temperature. I have not eaten commercial mayonaise since I was a child (actually I recall it was salad cream).
Given the staggering death toll in Italy (I can't say CMR because we don't know) I am less sure of the neutrality of oleic acid and plan to avoid it until this crisis has abated. Or maybe forever.
@ Cathy: spending most of my summer vacations in Italy, France, Spain, and Portugal, I can say that at least many Italians and some French have been getting fatter, and there is plenty of seed oil, prepared foods with seed oil, and crisps cooked in seed oil available in the supermarkets.
On the other hand, there are usually one or two brands of olive oil crisps in every supermarket, even Aldi.
This is another curve ball but I remembered a "fake" whooping cough epidemic years back. It is relevant because the RT-PCR can provide easily false positive results. The story is told here: https://www.nytimes.com/2007/01/22/health/22whoop.html . Could this be relevant here? My ex boss was monitoring norovirus years ago by testing oysters (in the Waitemata Harbour, Auckland) and discovered (via RT-PCR)that they were ALL infected. But of course they were not. They are filters and of course fragments of virus DNA will show up in them. They were perfectly healthy oysters.
And also incidentally; 150k-odd people have been sick enough to present to a hospital with COVID-19 symptoms and only 10% have tested positive. What is making the other 90% sick? Just thinking!
And another: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740125/ Page 10 is particularly interesting. The area in Italy most affected by COVID-19 has high air pollution.
@Eric - I have not been to Italy but I guess I have the old romantic view that they eat together, eat fresh whole foods (actually quite high SFA if the reseacrh I did years ago from Italian recipes was reflective of Italians' general diet). But for all I know they are scoffing MickeyDs and KFCs and drinking fizzy pop while popping statins and SSRIs and taking ASA for primary prevention of AECVD.
@Cathy in Manchester UK "I am less sure of the neutrality of oleic acid and plan to avoid it until this crisis has abated. Or maybe forever." Actually based on recent discussions that I have mostly read here, I gave up olive oil months ago. Have not made any mayonnaise for much longer than that, but would appreciate your recipe if you enjoy your dinner tonight.
@cavenewt - I still had to let it get softer out of the fridge first but it was delicious.
250g butter
1 whole egg (pasteurize if you worry anout salmonella)
15ml good Dijon mustard (Maille or Poupon)
Salt if using unsalted butter. Add garlic, pepper, sriracha but don't add too much liquid at this stage.
20mls of vinegar or lime juice.
Melt the butter on a low heat until just melted. Set aside and let cool to room temperature. Decant the butter fat into a jug trying to leave the milk solids behind (or not). You need a cheap hand blender (a £10 Tesco one will do) that has slots in the side and a small head and the container you use must not be too much wider than the head of the blender. Put the egg, mustard, salt and vinegar or lime. Add the butter all in one go. Let the eggy stuff sink and the butter come to the top (a few seconds). Hold the hand blender with the head resting on the bottom of the cup/jug completely flat. This bit is very important - whizz for minimum 20 secs without moving the blender head - not one mm. After 20-25 seconds you can start moving the head slightly so the rest of the butter gets incorporated. I added 20ml more water to try and get is softer when cold. Chill and enjoy.
I have a more expensive hand blender with a deeper head and jagged edges rather than slots and it does not work for mayonnaise. I am a slow foodie and was so grateful to find such a quick way of making mayo some years ago. I can't give credit because I can't remember where I saw it.
Oh my word this search for correlations has become addictive. I would not normally have this much time on my hands but until my work sort us for proper home working I get to indulge my inner nerd more than usual. And of course the increased risk of DEATH is always going to fuel curiosity.
Kind of old but not irrelevant link with hypomagnesaemia and risk of ARDS https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566971/ .
Erk, now I am worried - I take Mg+ daily but not an excessive dose but apparently it is a U curve. I have read in the past that factory farming has reduced the Mg+ in veggies by 50-60%. I don't take much as I have a low tolerance for the well known side effect and surely anyway hypermagnesaemia may indicate other pathology.
https://www.ncbi.nlm.nih.gov/pubmed/26205345
Phew - more likely in kidney failure. So most likely an association with more serious pathology than Mg+ level per se.
@Cathy in Manchester UK "Johnnyv can you please come up with a formulation for mayonnaise made with butter? Pretty please?" Your recipe is fine, as you note it needs to warm to become the correct consistency.
This is because the oil % of the emulsion(the discontinuous phase) is very high and there is very little water(the continuous phase) meaning the emulsion particles need to deform to move past each other which is fine when the oil is liquid but doesn't work when solid.
Now you make your mayonnaise by first having a water in oil emulsion that is phase inverted to a oil in water emulsion.
Now if you lowered the oil % at this point by adding more water after the phase inversion you would get a runny liquid, it would still be a stable emulsion but the continuous phase would increase so lipid particles could move freely past each other.
You could by slightly lowering the oil solids make a butter mayonnaise that was the correct consistency at fridge temp but as it warmed up to room temp it would liquefy so would be undesirable.
Too make your fridge to room temp butter mayo you would either need to modify the lipid phase to make the butter liquid at fridge temp or modify the water phase to introduce thixotropy and lower the lipid content so consistency came from water phase rheology.
MCT oil addition to the butter or lower solids and xanthum gum modification of the water phase perhaps.
Seems easier to let the mayo just get to room temp to be honest!
Johnnyv thank you so much. Physics was my weak point at school. Biochem - love it and can read all day. I really tried hard to understand quantum physics - got Nick Herbert's book wich is widely accepted to be QP for Dummies but could not get past chapter 4. All to abstract for me and my head wanted to explode. Seven differing theories, none provable, really??
Thanks johnnyv. CathyinManchester, Harold McGee 'On food and cooking, the science and lore of the kitchen' 884pp, is a classic reference on ingredients and techniques with quite a lot about emulsions and sauces and the uses of dairy products.
Hollandaise (mild, lemon) and Bearnaise sauces (made with a flavoured reduced vinegar) are egg yolk and butter sauces. Always a worry with raw egg yolks so in the Bearnaise, first adding the yolk to the acidic refuction at ph 4.5 or so stops the yolk proteins from curdling when you heat them as high as 90c. 70c is usually high enough to kill stuff. Then to beat in the softened butter, between 1/3 to 2/3. Just softened not melted. Butter has a uniquely wide temp range between those two states. Home made mayonaise when I was growing up tended to be thickened milk (with small amount of starch), vinegar added and/ or eggyolk with some mustard powder. Mustard is a good emulsifier. And lots of butter of course. Never ever any kind of oil. The remnant globule proteins in butter are also emulsifyng if you don't scorch them - butter is about 15% water. Whipping in butter to hot liquid foods at the last moment makes them nice and creamy.
Johnnyv, it's been years since we fooled with emulsions, but I can almost picture my boss talking in place of you. Lol! I remember do some cosmetics work for a company in FL and we had everything shipped down there so our formulation engineer could show them how it's made. When it showed up, all of the emmulsions had broke. FL was so much warmer than VA that time of the year and the thought didn't cross our mind to do some higher ambient temp test to make sure everything would remain stable. Talk about embarrassing. Lol! We did end up making a stable emulsion over much broader temp range.
I've made a lot of mayonnaise with a stick blender. I have got to try the butter recipe. Pass I like to put mustard powder in mine too. I wish I could post pictures here. Having 30+ laying hens on pasture gives me access to some awesome egg yolks too, especially this time of year when things are starting to green up.
Peter,
I am still confused re:cytokine storms. Have they been empirically observed or only hypothesized to account for demographic patterns in 1918 Spanish flu?
Are they property of certain viruses such that a healthy immune system is liable to raise the storm in response?
Why wouldn't a healthy immune system modulate and control itself. Presumably there are a host of self-regulation and negative feedback loops?
Hi Gyan,
Cytokine storms are simply a part of general pathology. There are, as you have guessed, a mass of positive and negative feedback loops to the immune system. Any form of major injury can provoke a cytokine storm, it is no way specific to viruses or any specific virus. Haemorrhage (even if the blood is replaced once “shock” has become established, about an hour or two) and gunshot wounds are also classics. So are sepsis, endotoxin shock and pancreatitis. But it is a bit random who goes in to full blown cytokine storm and then dies of multiple organ failure (terminally usually arriving at ARDS) at a given level of physiological insult. That’s where the cardiologists and their love of PUFA come in. The ROS intrinsic to a cytokine storm are easily propagated via PUFA and the PUFA derivatives activate the immune system still further. Humans are not designed to saturate themselves with linoleic acid. But even without such stupid diet choices, cytokine storms are a Real Thing. When you are terminally injured but not acutely dead, they are how you pass away.
It’s very established pathophysiology with which I have no argument, last PUFA opinions excepted.
Peter
And don't forget that "healthy volunteers" are not immune to cytokine storm and multi organ failure. I remember this when it happened - I am fairly sure one of these men was a Kiwi which is why it was big news over there. https://www.newscientist.com/article/dn10747-horror-clinical-trial-in-test-tube-recreation/
Ah, Northwick Park...
Most readers here know that statins are totally evil (given that there are better ways of lowering inflammation, which might arguably be their only benefit). But the mainstream is convinced that statins are a wonder drug. Smoke-and-mirror manipulation of statistics and disingenuous use of "relative risk" aside, it's still rather mystifying how exactly studies minimize the side effects.
Here's one clever technique used in studies of some other pharmaceuticals: add the same "inactive" ingredient to your placebo that causes the side effect in the pharmaceutical! Unfortunately, formulation of the placebo is often protected by proprietary information rules. https://drmalcolmkendrick.org/2020/02/25/the-great-placebo-scandal/
Green tea is suppose to help prevent cytokine storm. Some studies on it.
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