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Posts Tagged ‘antioxidants

more on oxidative stress and covid-19

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So, much of this piece will rely on Dr Seheult’s coronavirus update 65. We have this constant set of reactions in the body that reduce oxygen – adding electrons – until we get to water molecules, producing reactive oxygen species (ROS) along the way. This is often described as the oxygen metabolism process. Reactive oxygen species come essentially in three types, superoxides, hydroxy radicals and hydrogen peroxide. The three forms of the enzyme SOD, superoxide dismutase, convert superoxide into oxygen and hydrogen peroxide (H2O2), and then the H2O2 is reduced to H2O by means of glutathione peroxidase (GPx). The GPx, which is broken down in the process is recharged by the enzyme glutathione reductase (GR), which is in turn recharged by other antioxidant products. Also the enzyme catalase, which requires iron, can break H2O2 down into O2 and H2O.

People with diabetes, hypertension and overweight issues, among other things, may have compromised antioxidant systems (too many ROS), linked to angiotensin-converting enzyme 2 (ACE-2) and angiotensin-2. In creating ROS, oxygen is reduced to superoxide by means of the enzyme NADPH oxidase. So, as part of the renin-angiotensin system, angiotensin-2 (AT-2) is converted to angiotensin 1,7 (AT-1,7) by means of angiotensin-converting enzyme 2 (ACE-2). This is important because AT-1,7 effectively blocks superoxide production, while AT-2 promotes it. The virus SARS-CoV2 binds with, and so inactivates, ACE-2, preventing the production of AT-1,7. This action also means that there will be more AT-2 available, and so more superoxides. SARS-CoV2 also, according to Seheult, causes inflammation by recruiting polymorphonuclear neutrophils (PMNs), which stimulate production of superoxides by means of NADPH oxidase. So this, in essence, is why Covid-19 is bringing about oxidative stress.

Seheult next goes on to look at the research evidence for the preceding. A review article from 2005 points out that evidence from animal studies and cell culture studies shows that NADPH oxidase-derived oxidative stress is increased in vascular cells by AT-2, among other ‘agonists’ (chemicals that bind to receptors, thereby producing a response). Another article from 2012 describes several enzyme systems that act to form ROS, including ‘mitochondrial electron leakage from the electron transport chain’ as described in my previous post on the subject, and in Seheult’s update 63. It points out that ROS levels can rise dramatically in older people suffering from oxidative stress due to heart issues such as ischemia-reperfusion (referring to problems with oxygenated blood supply to the heart or other organs). It also points out that it has been shown experimentally that AT-2 stimulates an increase in ROS. A more recent article pertaining to SARS-CoV2 looked at patients in Wuhan and found a substantial increase in neutrophils in the most severe cases. Neutrophils cause ROS to be generated by NADPH oxidase. So Dr Seheult is carefully building up evidence for the case. The last point to deal with is AT-1,7 effects. Seheult has found a 2008 article entitled ‘Angiotensin converting enzyme 2 confers endothelial protection and attenuates atherosclerosis’. Seheult quotes the last line from the abstract:

These data indicate that ACE-2, in an AT-1,7-dependent fashion, functions to improve endothelial homeostasis via a mechanism that may involve attenuation of NADPHox-induced reactive oxygen species production. ACE-2-based treatment approaches may be a novel approach to limit aberrant vascular responses and atherothrombosis.

Atherothrombosis involves disruption of atherosclerotic plaques, which can be an immediate cause of heart attacks. Another article from 2015 essentially confirms the findings, as indicated by its title, ‘ACE-2 and AT-1,7 protect endothelial cell function and prevent early atherosclerosis by inhibiting inflammatory response’. A more recent article, from January 2020, describes how AT-1,7 administration improves endothelial function in women who have suffered from preeclampsia (vasoconstriction, high blood pressure and organ damage due to pregnancy). To give more detail, women in the last stages of pregnancy often suffer vasoconstriction and high protein levels, which is believed to be related to AT-2 levels. Researchers administered local AT-1,7, which is ‘an endogenous inhibitor of... AT-2′, to see if this reduced vasodilation and other symptoms of preeclampsia. What they found was that ‘AT-1,7 increased endothelium-dependent vasodilation via nitric oxide synthase-mediated pathways and attenuated AT-2-mediated constriction in women who have had preeclampsia, suggesting that AT-1,7 may be a viable therapeutic target for improve d microvascular function in women who have had a preeclamptic pregnancy’.

All of this is interesting in itself, of course, and is a little crash course in how research is helping us to tweak our immune systems, but in relation to Covid-19 these finding are of importance due to the comorbidities and general characteristics of patients being hospitalised with Covid-19. Dr Seheult, in his update 65 video, shows that, contrary to what was initially thought, i.e that Covid-19 is primarily a virus affecting the lungs and respiratory system, it may be much more of a problem for those with hypertension, cardiovascular issues and obesity – all of which are related to oxidative stress, as are diabetes and many forms of cancer. They contribute to endothelial dysfunction, which inevitably leads to oxidative stress, and may lead to thrombosis. Seheult here refers to a lengthy 2018 review article, ‘nutrients and oxidative stress: friend or foe?’, which among other things makes useful dietary suggestions for the combatting of oxidative stress – whole grains, nuts, fruit and vegetables, fish and legumes.

It’s been known for some time that endothelial cell dysfunction (ECD) can lead to thrombosis, as it is a major function of these cells to prevent thrombosis. The abstract from a 2002 study finds that ECD ‘is associated with decreased synthesis and oxidative inactivation of nitric oxide (NO)’ and it lists four types of antioxidant enzymes ‘essential for eliminating ROS that can inactivate NO’. It seems that the promotion of these enzymes can be associated with diet as above and with the reduction of risk factors such as hypertension, hypercholesterolaemia (high blood cholesterol), hyperhomocysteinaemia (homocysteine is an amino acid which can contribute to arterial damage and blood clots, and the condition is often associated with lack of vitamin B-12 or folate), cigarette smoking and diabetes mellitus. NO is the key molecule in maintaining endothelial function through these enzymes.

Now I’m having a look at Dr Seheult’s update 66 on blood pressure medications known as ACE inhibitors or ARBs. He cites an editorial article for the New England Journal of Medicine, on ‘inhibitors of the renin-angiotensin-aldosterone system and Covid-19’. This is a triple hormone system responsible for blood pressure regulation and fluid balance. Now, to return to what was outlined before, angiotensin-2 (AT-2) is converted to AT-1,7 by an angiotensin-converting enzyme (ACE-2). The SARS-CoV2 virus binds to the ACE-2 receptor and inhibits the enzyme’s production. This is problematic because AT-2 stimulates superoxide production (that’s bad), while the antioxidant AT-1,7 blocks it, so reducing oxidative stress. SARS-CoV2 also stimulates the production of PMNs, as above, which activates oxidative stress. Another part of this picture is that AT-1 is converted to AT-2 by ACE. There are blood pressure lowering medications, such as benazepril and lisinopril, aka ACE inhibitors, which reduce the production of AT-2. There are also angiotensin receptor blockers (ARBs), which may up-regulate ACE-2 (it isn’t clear, apparently). ACE inhibitors may do the same. The question being asked is, assuming these medications produce more ACE-2, will this lead to more infections because SARS-CoV2 has more ACE-2 to work with? Clearly it would be important to know whether to maintain these medications or not, that’s to say, whether these medications are a risk factor for contracting the virus or recovering from it. The above-mentioned article discusses three studies from different parts of the world, each involving thousands of participants. They all found no risks associating ACE inhibitors and ARBs with a higher risk of infection, severity of illness or death from Covid-19. One of the studies found that ACE inhibitors and statins were associated with a decreased risk of mortality, but these are observational studies and further research would need to be done.

So the above is a rather technical piece, highly reliant on the experts. I write to inform myself, and I’ve certainly been informed by writing this one. Apologies for its laboriousness, but I’ll be continuing… Please consult the references yourself if there’s anything you don’t understand.

References

Coronavirus Pandemic Update 65: COVID-19 and Oxidative Stress (Prevention & Risk Factors)

Coronavirus Pandemic Update 66: ACE-Inhibitors and ARBs – Hypertension Medications with COVID-1

https://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/ace-inhibitors/art-20047480

https://www.healthline.com/health/homocysteine-levels

https://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/ace-inhibitors/art-20047480

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831951/

Written by stewart henderson

July 16, 2020 at 4:21 pm

the low-down on antioxidants

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forget ORAC, just eat them coz they look so yummy

forget ORAC, just eat them coz they look so yummy

I’m going to risk alienating other colleagues here, but this post follows on from the last set in being inspired by work conversations, this time about plants and antioxidants. A plant was brought in by a staffer who apparently dabbles in naturopathy on the side, and its antioxidant properties were extolled. What do I know about antioxidants? Very little, except that some years ago red wine and various berries were being sold to us as containing life-enhancing quantities of these good molecules or whatever they are. It had something to do with binding to and neutralising ‘bad’ free radicals in our bodies. Of course I had no idea what free radicals were. Then later, via the Skeptics’ Guide to the Universe and other sources, I heard that the experts were back-tracking heavily on these life-enhancing properties.

So, what with being told in the staff room that antioxidants could cure cancer or some such thing, while elsewhere hearing that they’ve been wildly over-hyped, I’ve been considering for some time that I should do a post on these beasties, for dummies like me.

As usual, the first thing that greets me when I attempt to research this kind of thing is the pile of propadandist rubbish you have to wade through in order to find bona fide, science-based info sites. The good thing is that, over time, you get quicker at dodging bullshit.

I immediately homed in on a link saying ‘beware of antioxidant claims’, as being right up my alley. It took me to the ‘Berkeley Wellness‘ site out of the University of California. There I’m given the first definition – that an antioxidant is ‘a substance that helps mop up cell-damaging substances known as free radicals’, which leaves me hardly the wiser. I’m also told that selling products with claimed antioxidant properties is real big business in the US.

I’m also introduced to the ORAC (oxygen radical absorbance capacity) concept. My neighbour has an ORAC diet book and I’ve wondered what it meant. It seems that in the USA there’s a trend towards advertising the ‘antioxidant power’ of products based on ORAC scores – 7,300 ORAC units per 100 grams for a certain cereal, for example, or 6000 ORACs for a pack of corn chips. Are these numbers reliable, and what do they mean exactly?

Not much, apparently. The fact is that antioxidant interactions in the body are extremely complex and little understood. ORAC is only one of a number of different antioxidant tests used by different scientists in different labs, and even when they use the same test, such as ORAC, different labs come up with widely different results. Let me quote the Berkeley site directly:

Moreover, ORAC and other tests measure antioxidant capacity of substances only in test tubes. How well the antioxidants suppress oxidation and protect against free radicals in people is pretty much anyone’s guess.

A lot can happen to antioxidants once a food is digested and metabolized in the body, and little is known about their interactions. What has high antioxidant activity in a test tube may end up having little or no effect in the body. Preliminary research has found that when people eat high-ORAC foods, their blood antioxidant levels rise, but such results still don’t prove that this translates into actual health benefits.

The article ends with the usual smart advice. Choose a balanced diet, don’t eat too much, not too heavy on the meat, and with a fair quantity of whole grains, nuts and legumes, fresh fruit and veg, and you’ll get all the antioxidants and other nutrients you need. Actually, this article from I fucking love science, which gathers together expert advice on avoiding cancers, covers it all – keep your weight down, keep to the above-mentioned diet, exercise regularly in moderation, watch the sugar and salt intake and usually she’ll be right, whether it’s cancer, heart disease or whatever.

Not much more to say, really. But no doubt a lot more can be said about the science, and I’ll say just a bit about it here. Antioxidants, as the name suggests, are compounds that reduce oxidation in the body. Free radicals – unstable molecules – are produced when oxygen is metabolised. Free radicals remove electrons from other molecules, damaging DNA and other cellular material. They’re necessary for the body to function, but an overload can cause serious problems, and that’s where a common-sense diet comes in – though there are other factors which can bring about an overload, including stress, pollution, smoking (pollution by another name), sunlight and alcohol. Everything counts in large amounts.

Antioxidants come in many varieties. Nutrient antioxidants found in a variety of foods include vitamins A, C and E, as well as copper, zinc and selenium. Non-nutrient antioxidants, believed it have even greater effects (raising antioxidant levels), include phytochemical such as lycopene in tomatoes, and anthocyanins, found in blueberries and cranberries. I can’t find any clear info on the difference between non-nutrient and nutrient antioxidants, and it doesn’t appear to be important. There is, of course, a lot of ongoing research on all of this, and it would be easy to get obsessed with it all, raising your stress levels and sending those free radicals zinging through your body in legions. And if that’s what you want, why not buy this book, for a small fortune, and find out all that we currently know about how frying food affects its nutritive value, with particular attention to antioxidants. Of course, by the time you’ve finished it, it’ll likely be out of date.

There’s a ton of material out there on antioxidants, but Wikipedia is an excellent place to start, and to finish. One key piece of advice, in this as with other matters of diet, is – don’t rely on supplements when you can simply improve your diet (recent large-scale trials have shown they don’t work anyway). Get what you need from real food, as far as you can.

Written by stewart henderson

February 1, 2015 at 9:52 pm