a bonobo humanity?

So looking at the Medcram coronavirus update 82, approaching mid-June, we find that many of the monitoring websites give the impression that case rates are falling in the USA and elsewhere….

The update also looks at diabetes as a risk factor for covid-19. It discusses data from China linking mortality to blood sugar levels. Glycated haemoglobin (HbA1c) was brought up in a previous post, though there are different ways of measuring it – I’ll keep to the percentages. The normal HbA1c should be below 6%, though presumably not too far below, as can happen for diabetics that over-medicate. Your HbA1c measure tells you what your blood sugar level has been over the last two-month period, approximately. So, to quote from the study:

the researchers found an increased mortality risk associated with any form of previously undiagnosed elevated blood glucose at the time of admission among 453 patients hospitalised with laboratory-confirmed SARS-CoV2 infection

One would imagine that, with the oxidative stress that SARS-CoV2 brings on, diabetics or pre-diabetics not on medication might be more at risk than those on regular medication with a consequently relatively low HbA1c. This is the kind of association found here.

The update goes on to discuss an article on race and covid-19 mortality in England, which has a supposedly open-access National Health Service (NHS), which in fact has been subject to savage cuts from successive conservative governments. The article concludes, unsurprisingly, that BAME (i.e Black, Asian and Minority Ethnic) persons are ‘at increased risk of death from covid-19 even after adjusting for geographic region’. Suggestions for reducing these apparent inequities include ensuring adequate income protection, reducing occupational risks, reducing barriers in accessing healthcare and providing culturally and linguistically appropriate services. Of course, these problems exist within all countries with substantial immigrant populations, many of whom are more exposed to the virus than others.

Vitamin D is next revisited, with an article entitled ‘Vitamin D deficiency in Europe: pandemic?’, which was actually published back in 2016. Now I note from some of the comments on this update that there’s a lot of hype and apparent misinformation on vitamin D out there, so I want to dwell on this, for my own education.

The article refers to a Vitamin D Standardisation Program (VDSP) which has developed protocols to look at serum vitamin D data from differently-aged European populations, ‘to better quantify the prevalence of vitamin D deficiency in Europe’. So they applied these protocols to 14 different population studies, looking at serum 25-hydroxyvitamin D [25(OH)D]. Vitamin D has five different types, but the pertinent one for human health is D3, aka cholecalciferol, which is made by the skin when exposed to sunlight, and is also found in foods and supplements. D3 is hydroxylated by the liver at the ’25 position’, according to Seheult. Presumably this is a position on the D3 molecule where a hydroxyl group is added. 25(OH)D refers to the molecule after this hydroxylation, but before it becomes activated by further hydroxylation at position 1 by the kidney. So they looked at this molecule in a number of studies using ‘certified liquid chromatography – tandem mass spectrometry on biobanked sera’. Combined with other standardised serum data, data was collected from almost 56,000 patients, and the findings were that 13% of them, regardless of category, had serum levels seriously below normal, especially during the winter months. 40% were below the generally accepted norm. The problem was considerably exacerbated in dark-skinned ethnic sub-groups. 

Back to 2020, and an article looking at the role of vitamin D in the prevention of covid-19 infection and mortality. It noted that ‘Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland’, so this is obviously a covid-19 co-morbidity factor. The article goes on to describe the mechanism of vitamin D’s action in the body, the details of which I’ll pass over, but it does involve ACE-2 and angiotensin 1,7, and also many other factors including macrophage development. With all this they raise the question of widespread vitamin D supplementation, which is apparently a hot topic beyond strictly scientific media, as mega-doses of vitamin D are being argued for on certain social media platforms, and even in the comments to this update. There are messy arguments going around about safe upper limits. Dr Seheult simply reports the article’s concern about ‘popular information channels’ spruiking the use of vitamin D3 above the generally accepted safe upper limit of 4000 international units per day. There is of course a battle here, not only in relation to vitamin D3, between those who demand proper trialling and vetting of medications and supplements and those looking for quick fixes. In any case, modest, regular dosing of the vitamin seems to be most effective.  

Update 83 goes intensively into a very important and interesting health topic, which has been quite controversial and also revelatory of late; the role of fructose in our diet, and how it works in our bodies. So to refresh – which is always good for me, at least – about the issue of oxidative stress and how it is exacerbated by SARS-CoV2. So we have oxidative stress in the form of an excess of superoxide and reactive oxygen species (ROS). The SARS-CoV2 virus enters the cell via the ACE2 receptor, blocking angiotensin-converting enzyme 2 (ACE2) from converting angiotensin-2 (AT-2) to angiotensin 1,7 (AT-1,7). AT-2 promotes superoxide production, while AT-1,7 inhibits it. This problem is in addition to the effect of SARS-CoV2 itself in bringing about an increase in polymorphonuclear leukocytes (PMNs), which are white blood cells such as neutrophils, basophils and eosinophils. These also lead to increased superoxide production, and more oxidative stress. An essential feature of oxidative stress is that it can result in endothelial cell dysfunction. These cells line the vascular system that feeds the body’s major organs. This dysfunction brings about an increase in von Willibrand factor which leads to clotting and thrombosis. Recent analysis of autopsies found that covid-19 patients had nine times more lung clotting than control groups including influenza patients. 

So the point of all this is that not having oxidative stress in the first place will be an important prophylactic against the virus. As Dr Seheult relates from the coalface, it’s those with a high BMI, with kidney and cardiovascular issues, and with diabetes, that seem to be at most risk of succumbing to the virus. Also, those with apparently normal HbA1c but with increased glucose were about 10 times more likely to have serious complications associated with the virus. This raises the question of diet, specifically bad diet. 

We then go back to 2017 and an article, or compendium of articles, published in Nutrients. Its title is ‘fructose consumption in the development of obesity and the effects of different protocols of physical exercise on the hepatic metabolism’. So fructose is a simple sugar or monosaccharide which combines with glucose to form the disaccharide sucrose. There are two forms of fructose (and of glucose), which are enantiomers, which is to say they have opposite chirality, which gives them different reactive properties. They’e called D-fructose and L-fructose. They’re six-carbon sugars, and D-fructose is the prominent form in the body. Sucrose links together a molecule of glucose with one of fructose, so that sucrose (table sugar) is essentially 50% fructose. Fructose is added to many foods as a sweetener, particularly in the form of high fructose corn syrup (HFCS) and this has become controversial, in case you didn’t know. It’s not such as issue in Australia, where we mostly use cane sugar as a sweetener, but it features in imported processed foods, and in many sweetened drinks. So how does fructose impact on obesity and oxidative stress? To quote from the abstract of the above-named article, ‘studies indicate that fructose may be a carbohydrate with greater obesogenic potential than other sugars’. The article provides a compendium of such studies and how fructose affects glucose metabolism in the liver, adversely affects hepatocyte function and engenders inflammatory responses. It also advocates physical exercise for reduction of symptoms and as harm-minimisation practice. An experiment on rodents in which half were fed on fructose, the other half on sucrose (50% fructose, 50% glucose), the fructose-fed rodents gained more weight, and over time that extra weight involved an increase in abdominal adipose tissue and increased serum triglyceride levels:

Moreover, several studies corroborated the evidence that high fructose consumption might lead to accumulation of adipose tissue, systematic inflammation, obesity, oxidative stress and consequently insulin resistance in different tissues.

 And there’s much more on the same lines, with relevant references. Dr Seheult describes other articles and studies over the last ten years identifying fructose and HFCS and their relationship to type 2 diabetes prevalence. One interesting article, which looked at HFCS alone, and surveyed diabetes on a global level, found that ‘diabetes prevalence was 20% higher in countries with higher availability of HFCS compared to countries with low availability’ and these results were adjusted for BMI, population, GDP and other factors. Greatest use of HFCS was in the USA, which of course has the highest rate of diabetes, and is leading the world in covid-19 cases.  

References

Coronavirus Pandemic Update 82: Racial Disparities with COVID-19 & Vitamin D

Coronavirus Pandemic Update 83: High Fructose, Vitamin D, & Oxidative Stress in COVID-19

https://www.sciencedirect.com/science/article/pii/S0899900714001920