Wednesday, May 27, 2020

Fancy some serology? (3) In Japan

I notice that the COVID-19 state of emergency has been lifted in the last remaining areas of Japan as of last Monday.

I think they lost about 800 people in the pandemic. The seroprevalence in Tokyo is at least 6% in the populace attending a community clinic or two and at least 10% in healthcare workers. Exposure has widespread.

All countries have had their individual approaches to managing the pandemic, some sensible, others less so. What worked and what didn't will probably be lost in the avalanche of lies used to cover the arses of incompetent politicians, certainly here in the UK.

I found this ancient (2014) snippet by accident somewhere on t'internet:

"But one country has managed to keep obesity down with the help of a controversial government policy that probably wouldn't fly in the U.S. That country is Japan, where only about 3.5% of the population is classified as obese, compared to rates as high as 30% or greater in countries like the U.S. And it's not just a generally healthier diet and lifestyle that's kept the Japanese trim.

Citizens must adhere to government-mandated waistline limits or face consequences. The government has established waistline limits for adults ages 40 to 74. Men must maintain a waistline at or below 33.5 inches; for women, the limit is 35.4 inches. The "metabo law" went into effect in 2008, with the goal of reducing the country's overweight population by 25% by 2015. The government's anti-obesity campaign aims to keep "metabolic syndrome" — a number of factors that heighten the risk of developing diabetes and vascular diseases, such as obesity and high blood pressure, glucose and cholesterol levels — in check, thus minimizing the ballooning health care costs of Japan's massive ageing population.

Those who stray beyond the state-mandated waistlines are required to attend counseling and support sessions. Local governments and companies that don't meet specific targets are fined, sometimes quite heavily".


From Snopes (FWIW) it seems this is basically true, assuming the numbers for waistlines are real:

"Japan requires citizens between the ages of 45 and 74 to have their waistlines measured once a year and potentially seek medical attention.

Unlike individuals, however, companies and local governments can be assessed financial penalties if the citizens in their charge do not meet government standards".

I guess that having a national policy to limit metabolic syndrome might or might not have any influence of the course of a pandemic which targets people with metabolic syndrome.

We'll never know...

While the obvious initial advice for mitigating infection with SARS-CoV-2 was to try not to be elderly and to try not to be diabetic it now looks like simply trying not to be diabetic might have been all that mattered.

Peter

16 comments:

Eric said...

A bit off topic - being from Munich, I found this article by local researchers, who claim IL-6 to be a strong predictor for the need for mechanical ventilation: https://www.jacionline.org/article/S0091-6749(20)30685-0/abstract

According to this article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4194086/

"IL-6 seems to promote insulin resistance in hepatocytes (Senn et al, 2002) and endothelial cells (Yuen et al, 2009), but increases insulin sensitivity in skeletal muscle"

Doesn't this seem utterly beneficial in face of SARS-CoV-2? In other news, it is suggested to use IL-6 receptor antagonists, am I stupid to think this could backfire badly?

Peter said...

Oddly enough last night's FRCPath webinar was therapeutics. Blocking a single cytokine's action in the middle of a cytokine storm... Hahahahaha bonk. Hydroxychloroquine didn't fare too well (except if you are French) but zinc did. Sniggering at Remdesivir in the face of a cytokine storm is a reasonable approach.

Peter

cavenewt said...

It's risky making a comment before researching further but…I can't help wondering if Japan made any recommendations about *how* to keep one's waistline down.

Bob said...

Hi, cavenewt.

I did some "light" research. The Japanese "food-pyramid" looks more like a spinning top.

It seems to be grain and vegetable heavy, although there is certainly room for fish, meat, and eggs.

Japanese who "violate" the waist-circumference standards get "counseled", presumably using the Food Pyramid. It makes me wonder if Japanese in violation who become compliant also become hungry.

https://www.jacksonville.com/reason/fact-check/2016-09-16/story/fact-check-it-illegal-japanese-residents-be-overweight

This correspondence describes some "problems" with Japan's definition of metabolic syndrome.

This study suggests the Japanese (in Japan) consume a lot less sugar than, say, in the USA.

Gyan said...

Hydroxychloroquine is still officially approved in India as well and they claim that results have been good with little side-effects. But details are not forthcoming.

Are healthy people with properly functioning immune system in greatest danger of developing cytokine storm as it seems to be generally implied?

Gyan said...

About Japanese, I wonder how much of seed oils do they consume. Things like boiled rice, sushi etc are oil-less. But I suppose they must be deviating a lot from their traditional diets to develop metabolic syndrome in the first place.

It is curious about 2 servings of milk in the Japanese food pyramid. Are Japanese lactose tolerant or do they take some enzymatic aid to deal with lactose?

Peter said...

cave, my wife pointed out that Japanese nutritionists might be as incompetent as those in the rest of the world. Putting social and/or financial pressure on someone to stay hungry all of their adult life might just be a form of cruelty. Don't start me on slimming obese dogs using hypocaloric hunger generating foods. Is this animal cruelty? You can be prosecuted for having an overweight dog. How would the same dog feel, itself, if it is then starved to a normal weight?

Gyan https://pubmed.ncbi.nlm.nih.gov/8674324/ ARDS is the end result of a cytokine storm. Once started they are hard to stop. Best not go there in the first place. Sadly, by the time you are an eighty year old, insulin dependent type 2 diabetic in a nursing home you don't have much chance to get the linoleic acid out of your body as your hyperglycaemia suppresses the correct innate immune response to SARS-Cov-2. These folks do not have a normal immune system.

Peter

Gyan said...

Peter,
This paper sums over oleate and linoleate. I suppose their chemical analysis method obliges them to do so.
I guess the linoleate fraction is much more problematic than the oleate. The monounsaturated fats compose half of the cell membrane lipids per Wikipedia. So, they must be in the blood in concentration equal to the saturated fats (if the cells themselves do not synthesise the MUFA from SFA).

I wonder if linoleic acid a normal component of membrane lipids.

Peter said...

More enjoyment; https://www.gastrojournal.org/article/S0016-5085(20)34727-2/fulltext

Peter

Peter said...

BTW, not read that second paper yet but I'm a bit doubtful re albumin. FFAs are virtually never "free", usually bound to albumin. That doesn't seem to stop them doing damage...

Peter

Gyan said...

But again the lumping together of MUFA and PUFA!
which is annoying to those consuming significant amount of olive oil (though they shouldn't I guess).
Though in Fig D they only talk of C18:2 and C16:0 so I suppose PUFA is really meant by the term "unsaturated fats".

Spunk said...

Gyan on cell membrane for what it is worth I have been exploring these links which lead further into cellar maintenance. I think Peter is on the right track but this is from another perspective which I thinks adds to another aspect of the general problem in a subset of the population. Your more qualified opinion is appreciated.

http://www.medicinacomplementar.com.br/biblioteca/pdfs/Doencas/do-1195.pdf
https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/do-inositol-supplements-enhance-phosphatidylinositol-supply-and-thus-support-endoplasmic-reticulum-function/5B82B21F9BE2C05937D5F776919C6870/core-reader#

which when looked at the benefits from the page below..
Increasing cellular insulin sensitivity
Increasing fertility
Improved ovulation frequency by 300%
Increased low progesterone levels
Reduced serum insulin levels
Reducing raised serum androgens (testosterone) both free and total
Reducing glycosylated haemoglobin (HbA1c) an indicator of long term sugar levels
Reducing plasma triglyceride levels (the amount of fat in your blood)
Reducing (bad) LDL cholesterol
Increasing (good) HDL cholesterol
http://www.mypcos.info/1/dci/d-chiro-inositol-how-does-it-work/

This could bypass the natural process of plasmogen replacement which slows down after age 40 in those with SNP defects noticed in APOE4 that causes all the above.
https://www.sciencedaily.com/releases/2018/07/180724174225.htm

https://pubmed.ncbi.nlm.nih.gov/31022959/
Dr. Goodenowe has worked on plasmogens for 10 years and has come up with an absorbable formula.
I hope this gives some insight into the saturated fat dementia, and insulin resistance problem connection.

Spunk said...

The genetic defect is related to FADS2 and FADS1 SNPs regarding plasmogen production.

Detailed expaination by Dr. Goodenowe
on a video
https://www.youtube.com/watch?v=BfWBprgVFVc

Here is the metabolic part

The metabolic precursor to the blood and membrane plasmalogens (the vinyl ether phospholipid form) is the 1-O-alkyl, 2-acyl glycerol (free hydroxy at sn-3). Detailed structure activity of modulating specific plasmalogen species using specific alkyl-acyl glycerols is published here https://www.ncbi.nlm.nih.gov/pubmed/20546600. Of particular interest to the APOE e4 community is figure 8 which shows that only highly unsaturated fatty acid containing plasmalogens (C1, C9, C10) are effective at lowering cholesterol and that they do this by increasing cholesterol esterification (i.e. clearance). It is these same species that also lower amyloid levels. It is decreased levels of these species of vinyl ether phospholipids that have the strongest association with reduced cognition and increased mortality and it is these same species that we recently showed that high blood levels neutralize the e4 effect on cognition https://www.ncbi.nlm.nih.gov/pubmed/31022959. PPI-1011 is a non-natural precursor to the DHA 1-O-alkylglycerol (C1 in the above paper) that I invented in my drug development days to be orally bioavailable. The detailed bioavailability is published here https://www.ncbi.nlm.nih.gov/pubmed/22142382. My new plasmalogen oils are a natural version of PPI-1011 that in addition to DHA also contains EPA. The only difference is that instead of lipoic acid at sn-3 (which does not naturally occur), my new oils contain a fatty acid at sn-3 (which does naturally occur). I use DHA and EPA at sn-3 - so, as an added benefit, the new oils completely replace your current omega-3 supplements. In regards to PPI-1011 the neuroprotection was afforded from 10-50 mg/kg - which in a 75kg (~170lb) person is 750-3750mg/day, which is pretty reasonable. 1ml of the plasmalogen oil contains 900mg of the 1-O-alkyl-2,3-diacylglycerol. In regards to the bioavailability question, it is getting the DHA fatty acid from the dietary source, through the gut and then on to the blood phospholipids - specifically the sn-2 position of blood phospholipids that has to happen. 1-O-alkyl-2-DHA-3-OH is very good at this. Regular dietary phospholipids and triacylglycerols are digested to create free fatty acids in the gut - phospholipase A2 for phospholipids and lipases for triacylglycerols. These dietary components cannot transfer their sn-2 fatty acids directly to phospholipids in the blood. The free fatty acids have to find their way onto phospholipids. The plasmalogen oils deliver the DHA 1-O-alkylglycerol, which directly enters the biosynthetic pathway and retains the DHA as described in the linked papers.

I have no financial interest in this but I understand the cost is now around $300 US$ per bottle.
I hope it then can bring a lot of other people to the understanding it is not a cholesterol problem but something involved in the mitochondria as Peter is saying.
I am a male @ 73 and low fat is not sustainable but I appear to have this genetic problem and between two worlds.

Passthecream said...

Peter - re: zinc - an odd coincidence vs CV symptoms I noticed when I was reading up on zinc deficiency recently, it causes loss of the senses of smell and taste!

Puddleg said...

Not being elderly - Hmmn.

It seems that everyone over the age of 100 who has caught the Covid has recovered from it.
Survivorship bias - you won't get to live much past 90 with MetSyn.

cavenewt said...

Most excellent new word of the day: immunometabolism.

It's a known fact that obese people tend to get sick more and have chronic inflammation. I only wish the article had made clear (for the benefit of the general carb-eating public) that obesity is a symptom of metabolic ill health. Make special note of the reference to high blood sugar. We know how to deal with that, right?

"America’s Obesity Epidemic Threatens Effectiveness of Any COVID Vaccine"

https://khn.org/news/americas-obesity-epidemic-threatens-effectiveness-of-any-covid-vaccine/