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Monday, 22 November 2021

The Mother of all Conspiracies; Oswald and JFK in the 21st Century.




 

Imagine a counterfactual America, an alternative history wherein it has always been a well-known and accepted fact that Lee Harvey Oswald, a lone-wolf Marxist, had assassinated the President of the United States for rational Marxist reasons as well as subterranean personal ones. In this America, a school shooting by a paranoid vegan only encourages logical and evidence-based discussion of gun control and mental illness, a terror attack by Islamist hijackers is unanimously attributed to its obvious perpetrators, the Moon is American, and one cannot simply say that one has won an election which one has lost. It is an America in which Dr Fauci can sleep easy, and in which, sometimes, a virus is only a virus.
There were conspiracy theorists before JFK of course, indeed Oswald had tried to kill one of them, General Edwin Walker, the only human target he missed putting one or more bullets into. Yet the creative JFK theories have had a wider appeal across American society than the paranoic blend of European antisemitism and John Birch anti-communism indulged in by Walker and his contemporaries. Robert Kennedy, as Attorney General, tried to have Walker committed after he incited the Mississippi University race riots in 1962, but libertarian psychiatrist Thomas Szasz, opposed to the coercive psychiatry that was, to be fair, something of a public menace at the time, talked him out of it. Most people knew Walker was nuts. But with JFK theory you can stay respectable enough, it’s a hobby that seems to hurt no-one. You can put your own choice of villain in the frame – the CIA, the FBI, the Mafia, LBJ, the military-industrial complex, and of course the Cubans or the KGB, though it’s strange that the Manchurian Candidate option presented in film before the assassination – because it seemed believable at the time – hasn’t survived in the modern myth, which is comprised of scenarios entirely discordant with Oswald’s personal beliefs.

We know what Oswald’s political beliefs were because he wrote them down, and expressed them relatively freely to those around him, and we know how he wanted to express those beliefs because we have a reliable witness to his development as an assassin, Marina Oswald, née Prusakova, whom he married in Minsk during his defection to the USSR. A year after Lee’s death, Marina spent several months with Priscilla MacMillan, author of Khrushchev and the Arts; the Politics of Soviet Culture 1962-1964. (MacMillan, a friend of Kennedy’s, had also interviewed Lee Oswald during his defection to the USSR, at which time he told her “I want to give the people of the United States something to think about” - she was the only person to know both the assassin and his victim). The book that resulted, Marina and Lee, did not appear till 1977.
Marina Prusakova, who was not told her father’s identity but came to assume he had died in a purge, and who was rejected by her mother and step-father, was raised for a time by her devout grandmother in an Old Regime style. She had sensibly decided, from her observations of Soviet life growing up, that politics was a sickness and that anyone interested in politics was sick, but she made a fateful exception for the young American who was interested in her. Marina may not have been “political” but she knew a thing or two, as this statement to a Warren Commission interviewer shows:

I look at America. It’s all wonderful. But you go to the damn grocery store and it’s 200 varieties of cereal and basically it’s only oats, corn – how many things? Just so someone can make an extra million off of that. It’s just so unnecessary. If that’s progress, if that’s abundance, how stupid is it of us to want it? Three hundred bags of poison, maybe only two or three good – that kind of progress…I don’t think we should strive for.


Lee Harvey Oswald’s solitary Marxism was the ideology that allowed an intelligent young man to compensate for the loss of his father and an upbringing by one of history’s more blameable mothers. It provided him with inspiration for grandiose fantasies and daring acts, as well as a feeling of intellectual importance that compensated for learning difficulties, diagnosed posthumously as dyslexia. Oswald had become seriously interested in politics at the age of 15 or 16 after he was handed a leaflet about Julius and Ethel Rosenberg, who had been executed some two years earlier for spying for the Soviet Union, on a street corner in the Bronx (the effect this interaction had on him may have influenced his later decision to hand out Fair Play for Cuba pamphlets in New Orleans; it seems to have also triggered a Walter Mitty fantasy life as an espionage hero which lasted the rest of his life). “I was looking for a key to my environment, and then I discovered socialist literature,” Oswald wrote in his diary. “I had to dig for my books in the back of dusty shelves of libraries,” although according to Priscilla McMillan, he came across more as the naïve angry young man than a perceptive Marxist in their 5-hour Moscow interview despite using “a good deal of Marxist language”. The Oswald that stalks the pages of Marina and Lee is also a familiar character to readers of criminal profiling books, a case-study of the violent malcontent male loner. An American outsider who married a Russian outsider, and who was closer to Russian-speaking outsiders than to anyone else outside his family back in the USA, Lee Oswald read Orwell and Dostoyevsky, listened to Rimsky-Korsakoff, Chaliapin, Rachmaninov, and Tchaikovsky, and in his more constructive activities was inspired by Marxist newspapers The Worker and The Militant. He is holding copies of both these papers in the famous photographs Marina took of him with his guns, one of which, with a Russian inscription on the back – “hunter of fascists – ha ha ha!” in Marina’s hand, signed by Oswald, was given to their friend George De Mohrenschildt, the edgelord of the Dallas Russian émigré scene who parodies an éminence grise role in their story. The Worker was the paper of the U.S. Communist Party, The Militant of the Trotskyist Socialist Workers Party; Oswald corresponded with both journals, in a futile attempt to establish credibility as a leader of the organized left; the March 11 1963 copy of The Militant he is holding contains a letter headed “News and Views from Dallas”, signed LH, which was the high point of his association with organised socialism in America.



Lee Oswald was a person who would lie or withhold the truth whenever possible, so that he moved in a web of misdirection, but also presumably in a state of tension lest his lies (which include a long list of needless lies on official forms) be found out. He starved himself and Marina, as his mother had starved him, and pinched pennies as she had - what conspiracy asset would have been left as bereft of financial support as the Oswalds were at times, or as dependent on the kindness of strangers, who liked Marina but rarely liked ungrateful and ungracious Lee, and sometimes feared him? He was violent and controlling towards Marina, and beat her often, but became less violent at home after his attempted assassination of General Walker altered their relationship; he was also often cruel to her, as if practicing the heartlessness essential in a great revolutionary leader, and prevented her learning English for his own reasons (so that much of the evidence in the case of Lee Harvey Oswald is the record of conversations held in Russian, remembered by someone who thought in Russian). Yet Lee, who identified as a Marxist, was never a member of the Communist party, and recognised that the USSR was less successful than the USA – his core attitude was a juvenile delinquent’s hostility to any authority he was no longer capable of idealising, and a contempt for almost all other people, but as a strongly self-entitled person of progressive views he granted, in theory, everyone else a share in what he himself felt he deserved. As a social justice warrior, he was capable of admirable performative gestures, such as sitting in the black section of a segregated courtroom when arraigned in New Orleans, without seemingly ever going out of his way to perform any act of kindness for another human being in need.



There is a Jekyll and Hyde character to Lee’s politics, in which his violent acts contradict both his written statements and his progressive activism, resembling an expressionistic caricature of 20th century Marxism. Eleven years after his murder of Joseph P. Kennedy’s son, the Symbionese Liberation Army, collectivist Marxists with better childhoods and higher education than Oswald, embarked on a crime spree which included kidnapping the granddaughter of William Randolph Hearst. Their goals, motivations and grievances were, though filtered through the kaleidoscope of LSD, aligned with Oswald’s. Both Oswald and the SLA were influenced by what Elizabeth Converse, in The War of All Against All, called “the irrational Communist belief in ultimate world victory”. At its most extreme, this belief encouraged the accelerationist heresy - the belief that as Communism was inevitable, historical upheavals within Capitalist societies brought it closer, the worse the better. The accelerationist Marxist thinks like the addict who overdoses because the sooner they reach rock bottom, the sooner they can begin recovery. Thus the Communists of Weimar Germany were taught to welcome the rise of Hitler and call the liberal democrats who opposed him “fascists”, thus Posades welcomed the possibilities of nuclear war and alien invasion, thus the apocryphal Bernie bro voted for Trump. Sigmund Freud gave us the concept of Thanatos. the organism’s compulsive drive toward dissolution back into the world; Oswald’s decisions were often thanatic – his defection to the USSR, which involved cutting his left wrist and attempting to surrender his US citizenship, his assault on the Soviet bureaucracy to get both himself and Marina back to America, the time he shot at Walker, the time he stuck a pistol in his belt and said he was going to “have a look” at Richard Nixon (defused by Marina), the similarly defused planning to hijack an airliner to Cuba, the assassination itself, his refusal to consider that he might become a target afterwards.



On the morning of the 22nd of November 1963, Lee Oswald left $170 for Marina, whom he had, up to that point seldom allowed any cash at all, as well as the wedding ring he never took off, collected his rifle, and went to work at the Elm street branch of the Texas Schoolbook Depository. There, from a window on the East side of the fifth floor, he shot dead U.S. President John F. Kennedy and wounded John Connally, the Governor of Texas; later that day Lee Oswald would kill Patrolman J.D. Tippit with the cut-off Smith and Weston .38 pistol he had mail-ordered long before the rifle, but which had arrived on the same day.
Had Lee Oswald stood trial, his guilt would have been presented as a coherent narrative, and his motivations widely discussed, as he intended. Instead, he was shot dead two days later by Jack Ruby in an act almost as impulsive and last-minute as his own. Ruby’s motives are obscure – even more unstable and violent than Oswald, he was a heavy consumer of phenmetrazine, the new amphetamine also popular with The Beatles, was only 5 blocks from the assassination when it happened, and became paranoid that Jews would be blamed for the assassination, resulting in a pogrom.

The original complaint filed by the Dallas police department on Lee Oswald, around midnight on the 22nd of November, said that Lee Oswald did, "in furtherance of an international communist conspiracy, assassinate President John F. Kennedy,” but Oswald’s murder, and the lack of evidence against anyone else he knew, meant that charge would not be tested in a court of law.


The possibility that Oswald's political convictions may have played a decisive part in his shooting John F. Kennedy was down-played in the early 1960s because President Johnson and other officials did not want the assassination to become a casus belli with the Soviet Union. And to the public, this explanation, at a moment when capitalism was riding high, appeared ludicrous. Besides, for a Marxist, killing this president appeared wildly inconsistent. Kennedy was a liberal.
- Priscilla MacMillan, JFK and Oswald: The Inconvenient Truth


It may have also have mattered that no-one wanted to revisit McCarthyism. Sen Joseph McCarthy had been defeated by censure in 1954 and died in 1957; the House Unamerican Activities Committee lingered until 1975 but by 1963 was beginning to come under siege from an emerging counterculture that would become increasingly Marxist as the 60’s turned to the 1970’s. Overseas, US foreign policy and covert interventions would ensure the abduction, torture and death of many thousands of Marxists through the next few decades, yet in the USA the few leftists who knew Oswald were not persecuted, and the journals of which he said "you can see what they want you to do by reading between the lines" were not supressed.

In December of 1963 Dylan, then in the most activist stage of his folk career, was an attendee at a dinner event in New York hosted by the Emergency Civil Liberties Committee, which had awarded him its annual Tom Paine Award.


“I’ve got to admit that the man who shot President Kennedy, Lee Oswald, I don’t know exactly where — what he thought he was doing, but I got to admit honestly that I too — I saw some of myself in him. I don’t think it would have gone — I don’t think it could go that far. But I got to stand up and say I saw things that he felt, in me — not to go that far and shoot.”

The outraged crowd then expressed its hostility to the speaker.

“You can boo but booing’s got nothing to do with it. It’s a — I just a — I’ve got to tell you, man, its Bill of Rights is free speech and I just want to admit that I accept this Tom Paine Award in behalf of James Forman of the Students Non-Violent Coordinating Committee and on behalf of the people who went to Cuba.”

 

Fair play for Cuba.


Perhaps the first conspiracy theory about the assassination, after the statement of the Dallas PD, was held covertly – the branch of the CIA working on mind control research must logically have begun looking for evidence of a “Manchurian Candidate” brainwashing of Oswald by the KGB. The MKULTRA program, initiated in 1953, had failed to find any reliable form of brainwashing – they had been able to produce “vegetables” among their guinea pigs but not effective agents or reliable informants. The program’s budget would be reduced in 1964, but if there was the possibility that the Soviets or Cubans had succeeded in brainwashing Oswald then it could be kept alive, and perhaps vindicated. It was probably in this spirit that MKULTRA researcher Louis Jolyon West interviewed Jack Ruby in 1964, likely with the use of hypnosis and sodium pentothal. During the visit Ruby experienced a “psychotic break”, revisiting his delusion of a Kennedy-assassination inspired pogrom. Jolyon West, who killed the elephant Tusko with LSD and other drugs in 1962 and studied hippies with MKULTRA in Haight-Ashbury in late 1967, would later testify at the trial of temporary Marxist Patty Hearst in support of her defence’s brainwashing theory.

As Jolyon West was infiltrating the hippie subculture in search of the mind-control McGuffin, David Crosby was ending his career in The Byrds on stage at the Monterey Pop festival, by introducing the song He Was a Friend of Mine, a tribute to JFK, with a categorical statement of the most enduring of the JFK theories –

 

When President Kennedy was killed, he was not killed by one man. He was shot from a number of different directions — by different guns. The story has been suppressed, witnesses have been killed, and this is your country.


This moment marks the overground advent of progressive conspiracy theory, with its roots in Eisenhower’s Military-Industrial Complex warning, and its motivation in opposition to the Vietnam war, and more to the point, in opposition to the drafting of young American men, who naturally adapted conspiracy theory as a defence against the mass disposal of their minds and bodies by the State – analogous to the adoption of conspiracy theory defences today by those whose autonomy and future plans have been threatened by their conscription in the war against COVID-19. It was widely rumoured that LBJ, Kennedy’s Vice President and successor, under whom America had become most stickily entangled in Vietnam, had ordered the hit, but Richard Nixon and Henry Kissinger were about to show the USA, and the world, how real political conspiracies are constructed.

It was in this environment of renewed conspiracy ferment that Kerry Thornley, who had known Oswald in the US Marines and written a book inspired by his personality, The Idle Warriors, before the assassination, initiated Operation Mindfuck, with the help of Greg Hill, Robert Shea and Robert Anton Wilson. Operation Mindfuck introduced the Illuminati, through letters and ads in Playboy and other “hip” publications, to the US counterculture, with the intent of parodying the counterculture conspiracy industry and serving up an anti-stupidity vaccine with a side-order of chaos and fun. But Thornley and his accomplices underestimated the forces they were toying with, especially the human tendency to believe in malign machinations that can explain one’s own apparent impotence, dehumanise those in control, and undermine the achievements of those who have succeeded in one’s place, the same need to feel one’s weakness justified as cursed and, if one can do nothing worse, curse back that fed the belief in witchcraft in the Middle Ages and that in modern Africa.
While the Jews and Freemasons theories of the Right did not go away, they were quaintly old-fashioned and smelled strongly of old library books by the 1970’s, unable to keep up with the actual conspiracies and political and cultural developments of the Nixon-Kissinger period. The Satanic Abuse panic of the 80’s-90’s was the most successful attempt to upgrade them – arguably this succeeded, to the extent that it disrupted civil society, because it aligned with Marxist Feminist agitation against sexual exploitation; sexual Satanism was a predictable manifestation of the Patriarchy, and vice versa. Meanwhile, Hunter S Thompson had created new myths of the operation Mindfuck type, giving adrenochrome its backstory and planting a rumour about senator Eugene Muskie, the less-progressive Democratic candidate for the 1972 Presidential race, being high in ibogaine, which destroyed his candidacy. Kenny Thornley, instead of mocking the operation Mindfuck theories – which he, glimpsing the truth about Oswald, had started - began acting as if he believed in one or the other or all of them. And a young Oliver Stone, after serving in Vietnam and disapproving of the whole thing, began thinking about the assassination of JFK, who was believed posthumously to have been opposed to the War in some way.
Stone’s 1991 film JFK marks the moment when conspiracy theory passed over from the counterculture and far-right into the mainstream; it featured an impressive cast of A-list actors who presumably approved of its message of suspicion. JFK was followed by The X-Files TV series in 1993, with its telling slogan “I want to believe”. The X-Files was ironic enough, unlike Stone’s breathless film, but this didn’t inhibit the mass distribution and discussion of its ideas. Both JFK and The X-Files posit an all-powerful, yet successfully concealed Deep State for which the elected US government is window-dressing and easily removed if it objects. All around the world, this gave an easy explanation to those who resented US cultural hegemony and military power but were not the type to organise against them. It helped that it was a seemingly playful explanation, one that didn’t insist on being taken seriously enough to really test, even as it established itself in the zeitgeist.
Prior to 2001 the Deep State conspiracy theories had to co-exist with the rest of the Fortean world represented in The X-Files. UFOs, Bigfoot, spontaneous combustion, the Bermuda triangle, vampires - by the end of the 20th century, several different species of UFO-riding aliens were abducting and probing people all around the world. But after 9/11, Islamist terrorists became the aliens and monsters we watched out for and it was the US state that began abducting and probing people everywhere; reports of UFO sightings and alien abductions went into serious decline. As the plainly venal team of Bush, Cheney and Rumsfeld openly conspired to roll back freedoms and push the world into another unwinnable war, a spontaneous conspiracy of sorts arose to undermine their casus belli by suggesting that the terror attacks had been an inside job. This also meant not admitting that a Saudi Arabian NGO could get the better of the mighty USA, so it had cross-party appeal, but the list of progressive celebrities who endorsed or indulged 9/11 conspiracy theories is almost as impressive as the cast of JFK, and included Ed Asner, Spike Lee, Woody Harrelson, Rosie O’Donnell, Marion Cottillard and Graham Nash. Spreading a rumour like “Bush did 9/11” is a way of cursing the powerful, a displacement activity born of impotence and frustration, like spreading a rumour that your local feudal tyrant worships Bahomet because you are powerless to stop him taking what he wants from you. And 20 years later, Q-Anon is simply the aggregate of all the progressive counterculture conspiracy theories, including Kerry Thornley and Hunter S Thompson’s inventions, with a modified Satanic abuse element, and with the older Jews, Freemasons and Communists theories always sneaking back in.

It all began with Oswald and the trauma he induced in the USA on
November 22 1963. As NBC News anchor David Brinkley said, as he signed off that night, Kennedy’s death was “just too much, too ugly and too fast.” In 2007 Priscilla MacMillan summed up the aftermath of the assassination in a short article for World Policy Journal titled JFK and Oswald: The Inconvenient Truth.


 Oswald's act of violence indisputably ushered in an era of unease and suspicion in American life that was not there prior to the Kennedy assassination. Oswald was not responsible for all of the damage that has befallen American society since 1963, much as he would have wished to be. Some of that damage is the result of events related only tangentially to the assassination of President Kennedy. But some of the injury can, with justice, be attributed to conspiracy theorists who have gone to superhuman lengths to avoid facing the truth. They have constructed wildly-implausible scenarios, far-out, fictitious "conspirators," and have scandalously maligned the motives of Kennedy's successor, rather than take a hard look at the man who actually did it. They have, ironically, done more to poison American political life than Lee Oswald - with the most terrible of intentions - was able to do.

Kerry Thornley thought that a little light Illuminati hoaxing would make people immune to conspiracy theories, but conspiracy theories, as The X-Files and its spin-off The Lone Gunmen have proved, are immune to spoofing; Q-Anon is a spoof of spoofs, and it has outshone them all.

If the world is ready to give Marina Oswald’s story and Priscilla MacMillan’s research and analysis the same attention it once gave to Jim Garrison’s speculations, narrative will replace montage in the JFK storytelling tradition. In the near future there will be a film, or better yet a TV series, of Marina and Lee, based on the True Crime book of that name which its viewers will queue to read. In our contemporary state of disinformation hypersensitivity, it should get a more reasoned reception from the comments section than the PBS Frontline documentary series Who Was Lee Harvey Oswald did when it rescreened in 2013. We will come to understand Lee Oswald and the ideological world he inhabited, which is closer to our own than used to be the case, because the expression of low-constraint or heretical or otherwise deviationist versions of Marxist ideas is now commonplace, because glasnost revisionism, 90 Day Fiancé, RT, and Red Scare have made Marina’s voice more relatable, and because we’re now well-used to seeing violent malcontent male loners acting out the terrorist fantasies which they developed through ideological study and travel.

Imagine a counterfactual America, an alternative history wherein it has always been a well-known and accepted fact that Lee Harvey Oswald, a lone-wolf Marxist, assassinated the 35th President of the United States.



George Henderson, Auckland, Sept 2021

Addendum:
The killing of Oswald by Jack Ruby was the real singularity that tipped America down the path to Q-Anon, as it removed Oswald from his own story. I've called Ruby's motives "obscure" above, but obscure as they are they are not beyond all speculation. Here's what I think.

Roy Cohn, as a patriotic American Jew trying to succeed in the system, persecuted Jewish American communists because he thought they gave a bad impression of American Jews - he more-or-less framed Ethel Rosenberg and brought about her execution. This was the injustice that led to the radicalization of the young Oswald.
The Dallas newspapers had been carrying adverts against JFK that in the opinion of many at the time amounted to hate speech, and some of these were signed by Jewish Republicans (the Republican party still being the old party of tolerance for many, I suppose). Ruby was concerned about this even before the shooting, and when he heard about it panicked that the Jews would be blamed for killing JFK (as, I suppose, they had been for killing Christ) and was compelled to kill Oswald to clear their name, as a kind of sacrificial lamb for his people.
Because this involved magical thinking, and because he may have found it embarrassing in his lucid moments, Ruby gave the more innocent explanation that he had killed Oswald to spare Jackie Kennedy the pain of a trial.
Roy Cohn would go on to become the mentor of Donald Trump, and Donald Trump would go on to become the patron and beneficiary of Q-Anon.







Saturday, 20 November 2021

Selenium reduces COVID-19 risk - a back-of-the-envelope Bradford Hill analysis [originally posted 28/09/20, last updated 23/11/21]







Bradford Hill introduced a checklist for assessing the strength of epidemiological evidence for causality, which is useful in the current pandemic when nutritional factors have been insufficiently tested by experiment in favour of drugs with, so far, relatively weak effects.[1]
Remember, a long time has passed and a lot of people have died while Evidence-Based Medicine was facing the wrong way.
And asking the wrong question. "What new treatment will save more lives in the ICU?" is an important question, but one with few answers and no great ones - "What can stop people who catch SARS-CoV-2 coming to the ICU?" is a better one in a pandemic, and one that might also lead to better treatment protocols.


Selenium reduces COVID-19 mortality: A Bradford Hill analysis

1) Strength of association. Very Strong.


a) On inspection of the Hubei data, it is notable that the cure rate in Enshi city, at 36.4%, was much higher than that of other Hubei cities, where the overall cure rate was 13.1% (Supplemental Table 1); indeed, the Enshi cure rate was significantly different from that in the rest of Hubei (P < 0.0001). Enshi is renowned for its high selenium intake and status [mean ± SD: hair selenium: 3.13 ± 1.91 mg/kg for females and 2.21 ± 1.14 mg/kg for males]—compare typical levels in Hubei of 0.55 mg/kg (10)—so much so that selenium toxicity was observed there in the 1960s. Selenium intake in Enshi was reported as 550 µg/d in 2013.
Similar inspection of data from provinces outside Hubei shows that Heilongjiang Province in northeast China, a notoriously low-selenium region in which Keshan is located, had a much higher death rate, at 2.4%, than that of other provinces (0.5%; P < 0.0001). The selenium intake was recorded as only 16 µg/d in a 2018 publication, while hair selenium in the Songnen Plain of Heilongjiang was measured as only 0.26 mg/kg (Supplemental Table 2).

Finally, we found a significant association between cure rate and background selenium status in cities outside Hubei (R2 = 0.72, F test P < 0.0001; Figure 1, Supplemental Table 2).[2]




Correlation between COVID-19 cure rate in 17 cities outside Hubei, China, on 18 February, 2020 and city population selenium status (hair selenium concentration) analyzed using weighted linear regression (mean ± SD = 35.5 ± 11.1, R2 = 0.72, F test P < 0.0001). Each data point represents the cure rate, calculated as the number of cured patients divided by the number of confirmed cases, expressed as a percentage. The size of the marker is proportional to the number of cases.



b) Serum samples (n = 166) from COVID-19 patients (n = 33) were collected consecutively and analyzed for total Se by X-ray fluorescence and selenoprotein P (SELENOP) by a validated ELISA. Both biomarkers showed the expected strong correlation (r = 0.7758, p < 0.001), pointing to an insufficient Se availability for optimal selenoprotein expression. In comparison with reference data from a European cross-sectional analysis (EPIC, n = 1915), the patients showed a pronounced deficit in total serum Se (mean ± SD, 50.8 ± 15.7 vs. 84.4 ± 23.4 µg/L) and SELENOP (3.0 ± 1.4 vs. 4.3 ± 1.0 mg/L) concentrations. A Se status below the 2.5th percentile of the reference population, i.e., [Se] < 45.7 µg/L and [SELENOP] < 2.56 mg/L, was present in 43.4% and 39.2% of COVID samples, respectively.
The Se status was significantly higher in samples from surviving COVID patients as compared with non-survivors (Se; 53.3 ± 16.2 vs. 40.8 ± 8.1 µg/L, SELENOP; 3.3 ± 1.3 vs. 2.1 ± 0.9 mg/L), recovering with time in survivors while remaining low or even declining in non-survivors.[3]

c) Vitamins B1, B6, B12, D (25-hydroxyvitamin D), folate, selenium, and zinc levels were measured in 50 hospitalized patients with COVID-19. A total of 76% of the patients were vitamin D deficient and 42% were selenium deficient. No significant increase in the incidence of deficiency was found for vitamins B1, B6, and B12. folate, and zinc in patients with COVID-19. The COVID-19 group showed significantly lower vitamin D values than the healthy control group (150 people, age/sex matching). Severe vitamin D deficiency (based on 10 ng/dL) was found in 24% of the patients in the COVID-19 group and 7.3% of the control group. Among 12 patients with respiratory distress, 11 (91.7%) were deficient in at least one nutrient. However, patients without respiratory distress showed deficiency in 30/38 people (78.9%, P-value 0.425). These results suggest that a deficiency of vitamin D or selenium may decrease the immune defenses against COVID-19 and cause progression to severe disease; however, more precise and large-scale studies are needed.[18]

100% of the patients in this study with severe outcomes, including death, were selenium deficient; 75% were vitamin D deficient; none were zinc deficient.

d) In regression models, serum Se levels were inversely associated with lung damage independently of other markers of disease severity, anthropometric, biochemical, and hemostatic parameters.[23]

e) The association between soil Se level and the incidence of COVID-19 was observed in different cities of Hubei Province. The incidence of COVID-19 was more than 10 times lower in Se-enriched cities (Enshi, Shiyan, and Xiangyang) than in Se-deficient cities (Suizhou and Xiaogan).[25]

See also refs 19 and 22, discussed below.



2) Consistency - Very Strong

All epidemiological data about selenium and COVID-19 is consistent in direction and effect size. However, tests that could be done comparing COVID-19 risk in high and low selenium regions of Brazil, Scandinavia (selenium is supplemented in the food supply of Finland), and the USA would establish consistency further.

[edit 16/11/202o] - New study from South India is consistent with those from Germany, China, and South Korea:

We analysed the blood serum levels in apparently healthy (N=30) individuals and those with confirmed COVID -19 infection (N=30) in the southern part of India. Patients showed a significantly lower selenium level of 69.2 ±8.7 ng/ml than controls 79.1 ± 10.9 ng/ml, the difference was statistically significant (P=0.0003). Interestingly the controls showed a borderline level of selenium, suggesting that the level of this micronutrient is not optimum in the population studied.[19]

[edit 14/12/2020] letter from Finland in BJN compares death rate with Sweden's.

[edit 15/12/2020 deficiency of both zinc and selenium predicts COVID-19 severity in EPIC data]
"This combined deficit was observed in 0.15% of samples in the EPIC cohort of healthy subjects, in 19.7% of the samples collected from the surviving COVID-19 patients and in 50.0% of samples from the non-survivors."[22]

Statistically significant and often very strong associations between selenium intake, selenium status, and various COVID-19 outcomes have been reported from China, South Korea, Germany, South India, Russia and Europe. No null association has yet been reported.

Rigorous re-analysis of updated Chinese pandemic data published recently confirms the original observations, this time using the case-fatality rate:

A total of 147 cities each reporting over 20 cases were included in the current analysis. In these cities, 91% (14,045) of total cases and 85.8% (103) of total mortality from COVID-19 in China had been reported.
Totally, 14,045 COVID-19 cases were reported from 147 cities during 8 December 2019–13 December 2020 were included. Based on selenium content in crops, the case fatality rates (CFRs) gradually increased from 1.17% in non-selenium-deficient areas, to 1.28% in moderate-selenium-deficient areas, and further to 3.16% in severe-selenium-deficient areas (P = 0.002). Based on selenium content in topsoil, the CFRs gradually increased from 0.76% in non-selenium-deficient areas, to 1.70% in moderate-selenium-deficient areas, and further to 1.85% in severe-selenium-deficient areas (P < 0.001). The zero-inflated negative binomial regression model showed a significantly higher fatality risk in cities with severe-selenium-deficient selenium content in crops than non-selenium-deficient cities, with incidence rate ratio (IRR) of 3.88 (95% CIs: 1.21–12.52), which was further confirmed by regression fitting the association between CFR of COVID-19 and selenium content in topsoil, with the IRR of 2.38 (95% CIs: 1.14–4.98) for moderate-selenium-deficient cities and 3.06 (1.49–6.27) for severe-selenium-deficient cities
.[24]

UPDATE 23/11/2021

A recent review of in-hospital selenium data shows consistent associations between lower Se and adverse outcomes in 9/10 comparisons where the population selenium level is below the optimal range of 130-150 mcg/dL. The outlier is an n=9 study (the smallest) in which length of hospital stay is the outcome and supplementation during the stay may be a confounder. In the one study where Se went over the optimal range a higher Se was found in more severe cases.[26]

3) Specificity - Strong

Selenium has much weaker or less consistent associations with other diseases, except those caused by other RNA viruses, e.g. when risk of hepatocellular cancer in viral hepatitis patients is compared with risk of osteoporosis.[4, 5]


4) Temporality - Strong

Prospective ecological comparisons are temporal by design.[2] In the German study, the temporal association between low serum selenium levels and COVID-19 symptom severity was closely tracked.[3]

Nutrients 12 02098 g003 550

5) Dose-response gradient - Very Strong

A strong, consistent dose-response is seen, even at levels where the risk of selenium toxicity exists, and despite the fact that toxic levels of soil selenium are often a legacy of industrial pollution in China.[2]


6) Plausibility - Very Strong

Reading references 2 and 3, as well as this review of the evidence written before reference 2 was published, should be persuasive.[6] See also ref 17 for antiviral effects. The effects of selenium and selenite align to support the associational results across multiple mechanisms.


7) Coherence - Very Strong

Selenium is well-studied and nothing in its story seems to contradict the idea that higher intakes will protect against COVID-19 mortality and reduce the severity of disease.
Dexamethasone, a drug which can reduce COVID-19 mortality in the ICU, enhances 1α,25-dihydroxyvitamin D3 effects by increasing vitamin D receptor transcription.[7] 
Selenium sufficiency is essential for the function of vitamin D in peripheral blood monocytes.[8] Vitamin D status also correlates with COVID-19 survival.[9]

[Edit: 20/11/20] Two conditions which are associated with selenium depletion through effects on tubular mineral resorption, sickle cell disease (aOR, 1.73; 95% CI, 1.21-2.47), and chronic kidney disease (aOR, 1.32; 95% CI, 1.29-1.36), are the comorbidities most strongly associated with COVID-19 mortality in a large US MEDICARE patient analysis.[20] Selenium status in sickle cell disease is inversely associated with markers of hemolysis, a feature of severe COVID-19 pathology.[21]


8) Experiment - Weak (Neglected)

This is an area of sufficient neglect to make you despair about medical humanity, if you know that there have been thousands of trials of potentially useless drugs for COVID-19 already. However this criteria overlaps with the next section as there are several trials of selenium supplementation in other viral diseases, and animal experiments in analogous conditions, and many mechanistic experiments that are non-specific. The interaction between SARS-CoV-2 and selenoproteins has been confirmed by experiment.[10]

UPDATE 23/11/15

This team in Wuerzburg Germany have ben steadily researching selenium in COVID-19 patients in ICU and have got to the stage of testing an intervention.
There's no control arm but we have proof of safety for 1mg sodium selenite and proof of concept in that people in whom the intervention raised SelenoP did better.
We don't yet know that this effect isn't an artifact of disease severity, but such careful work brings the needed RCT closer.

"According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (rs = −0.495), PCT (rs = −0.413), IL-6 (rs = −0.429), IL-1β (rs = −0.440) and IL-10 (rs = −0.461). Positive associations were found for CD8+ T cells (rs = 0.636), NK cells (rs = 0.772), total IgG (rs = 0.493) and PaO2/FiO2 ratios (rs = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.[27]

In comparison to patients with a fatal outcome (n = 8), survivors (n = 14) significantly responded to supplementation with an increase in Se (p = 0.008), SELENOP (p = 0.004), GPx3 (p = 0.039) and Zn levels (p = 0.020) over the course of the ICU stay (Figure 5). Decedents had a median ICU course of 17.5 days (12–22), whereas patients with a favorable outcome were treated for significantly longer (40 days, 20–44; p = 0.025)."

There are also two tests of mixtures including selenium for COVID-19 with favourable results, the first is a survey of a clinic's patients already taking selenium, zinc, and vitamin D for  Hasimoto's thyroiditis.[28]

After adjusting for age, gender, BMI, smoking status, we found an association between the absence of supplements and the risk of hospitalization, and invasive mechanical ventilation. Patients with Hashimoto’s thyroiditis who had COVID-19 infection and who had previously taken supplements such as selenium, zinc, and vitamin D had milder clinical outcomes, or no symptoms compared to those who did not receive supplements who had a moderate or severe outcome (P <0.05)

The next is an RCT from the South Indian doctors cited earlier, of a mixed supplement supplying 40 mcg selenium (a very modest dose in this context, but not insignificant), n=100.[29]


ImmuActiveTM 500 mg capsule containing curcuminoids (100 mg), andrographolides (50 mg), resveratrol (50 mg), zinc (10 mg), selenium (40 mcg), and piperine (3 mg) or placebo was administered orally to subjects once daily after breakfast.

Results. The ordinal scale at the end of the study was significantly lower in COVID-19 patients supplemented with ImmuActive (0.57) than placebo (1.0), with a  value of 0.0043. The ordinal scale decreased by one unit within 2.35 days in ImmuActive-supplemented patients, while it took 3.36 days in placebo-supplemented patients. Days of hospitalization and time required to turn RT-PCR negative were comparatively lower in the ImmuActive arm than the placebo arm. Change in modified Jackson’s Symptom Severity Score and COVID-19 QOL were significant from screening to the end of the study in both ImmuActive and placebo arms. There were no adverse events observed during the study period.





9) Analogy - Strong

Selenium intake is protective, and selenium supplementation has been useful, in other viral illnesses.
However, the protective effect of high selenium intakes before infection in epidemiology appears stronger than the protective effect of selenium as a late intervention in disease.[6, 11]



Those are the nine canonical Bradford Hill criteria. The discussion about selenium suggests that an ad hoc 10th criteria will also be useful:

10) Risk - Weak in short-term, Well-Established in long term.

We can add the most relevant of extra questions to any given set of criteria - "strength of the alternative hypothesis" would be a good one for any lipid hypothesis.
Bradford Hill stated that some interventions are easier to justify than others.

On fair evidence we might take action on what appears to be an occupational hazard, e.g. we might change from a probably carcinogenic oil to a non-carcinogenic oil in a limited environment and without too much injustice if we are wrong. But we should need very strong evidence before we made people burn a fuel in their homes that they do not like or stop smoking the cigarettes and eating the fats and sugar that they do like. In asking for very strong evidence I would, however, repeat emphatically that this does not imply crossing every ‘t’, and swords with every critic, before we act.[1]

With nutrient intakes there is often an identifiable risk, with a J-shaped curve. With selenium the risk is selenosis, which is a condition that requires chronic high exposure (I have given myself mild selenosis with around 900mcg selenium a day and it was not a terrible condition to experience and was reversible). There could be other risks. Luckily we have an experiment that tells us where the limit is.
In a low selenium country, like New Zealand or Denmark, you don't want to take more than 200mcg of extra selenium long term.[12] Pity the low dose arms here weren't retained in the intervention.


fx1

During 6871 person-years of follow-up, 158 deaths occurred. In an intention-to-treat analysis
the hazard ratio (95% confidence interval) for all-cause mortality comparing 300 µg selenium/d to placebo was 1.62 (0.66, 3.96) after 5 years of treatment and 1.59 (1.02, 2.46) over the entire follow-up period. The 100 and 200 µg/d doses showed non-significant decreases in mortality during the intervention period that disappeared after treatment cessation. Although we lacked power for endpoints other than all-cause mortality, the effects on cancer and cardiovascular mortality appeared similar.



Howsoever that may be, taking extra selenium above 200mcg per day may yet be advised if one becomes ill with COVID-19,  but an inorganic salt of selenium like sodium selenite (which is anyhow probably safer than the selenomethionine form long-term, as I'll discuss below) is preferable, according to the selenovirus expert, Ethan Will Taylor. 
(this video link does not show in the mobile version of this post but can be reached through the web view option at the bottom)



[Edit: 1/09/20] There is also very good evidence that intravenous high dose selenite is safe in the ICU setting.

Totally 19 RCTs involving 3341 critically ill patients were carried out in which 1694 participates were in the selenium supplementation group, and 1647 in the control. The aggregated results suggested that compared with the control, intravenous selenium supplement as a single therapy could decrease the total mortality (RR = 0.86, 95% CI: 0.78–0.95, P = .002, TSA-adjusted 95% CI = 0.77–0.96, RIS = 4108, n = 3297) and may shorten the length of stay in hospital (MD −2.30, 95% CI −4.03 to −0.57, P = .009), but had no significant treatment effect on 28-days mortality (RR = 0.96, 95% CI: 0.85–1.09, P = .54) and could not shorten the length of ICU stay (MD −0.15, 95% CI −1.68 to 1.38, P = .84) in critically ill patients.[13]

This, and an earlier analysis which found less benefit, did not single out viral illnesses as a subgroup - this is only evidence for safety - but the earlier analysis did find a) slightly lower mortality in trials without an initial bolus dose, b) no increased risk in patients with renal disease.[14]

I will hypothesize briefly on selenium increasing mortality at 300 mcg/day in the Danish intervention study, a dose far too low to cause selenosis.
(The conventional signs of selenosis result from selenocysteine replacing cysteine in proteins, and the relative weakness of the Se-Se bond compared with the S-S bond.)
[Edit - hypothesis improved, 23/09/20]
The question of selenium causing insulin resistance and increasing mortality in high-dose supplements, not mirrored as far as I can see in natural high-dose populations, may have a simple explanation - supplements allow us to consume micronutrients without protein.
If you have no cysteine or methionine coming in when you take Se (either because you're not eating protein, or perhaps it can happen naturally if the Se level is high in a low-protein food and diet) then the selenocysteine formed will be incorporated into all proteins, not just the ones that require it. Including the insulin receptors, which will suffer a relative loss of function.
(similarly, though for different reasons, pyridoxine toxicity can be triggered by supplementing on a low-protein diet)

If we think that insulin resistance causes CVD, then the increased risk from (mostly) natural high Se levels is not great, see fig 5 here [15], but the intervention studies have more alarming results, and I think the competition of selenium- vs sulphur-amino acids in protein fed vs unfed states can explain this. There is next to no evidence of Se toxicity from Brazil nuts, which are high in both Se and protein.



It makes sense to me that selenomethionine, very useful as it will increase selenoprotein levels quickly if you don't have much time, should be replaced with sodium selenite for long-term coverage.

Brazil nuts are a variable quantity, a sample of nuts sold in NZ in 2008 had an average of 19 mcg per nut and increased selenoprotein levels more than selenomethionine.[16]

Plasma selenium increased by 64.2%, 61.0%, and 7.6%; plasma GPx by 8.3%, 3.4%, and -1.2%; and whole blood GPx by 13.2%, 5.3%, and 1.9% in the Brazil nut, selenomethionine, and placebo groups, respectively. Change over time at 12 wk in plasma selenium (P < 0.0001 for both groups) and plasma GPx activity in the Brazil nut (P < 0.001) and selenomethionine (P = 0.014) groups differed significantly from the placebo group but not from each other. The change in whole blood GPx activity was greater in the Brazil nut group than in the placebo (P = 0.002) and selenomethionine (P = 0.032) groups.

[Edit 02/09/20] - thanks to Mike Angell for this link; while all selenium sources are probably protective against death and ongoing harm from COVID-19, only selenite is likely to have an additional antiviral effect, and has low toxicity.[17]

A rational protocol for using selenium in prevention and treatment of COVID-19, fully consistent with the evidence discussed here, is described at the end of this paper:
https://www.frontiersin.org/articles/10.3389/fnut.2020.00164/full



All scientific work is incomplete - whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time.

Austin Bradford Hill, 1965.






References:

[1] Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58(5):295-300.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1898525/pdf/procrsmed00196-0010.pdf

[2] Jinsong Zhang, Ethan Will Taylor, Kate Bennett, Ramy Saad, Margaret P Rayman, Association between regional selenium status and reported outcome of COVID-19 cases in China, The American Journal of Clinical Nutrition, Volume 111, Issue 6, June 2020, Pages 1297–1299, https://doi.org/10.1093/ajcn/nqaa095

[3] Moghaddam, A.; Heller, R.A.; Sun, Q.; Seelig, J.; Cherkezov, A.; Seibert, L.; Hackler, J.; Seemann, P.; Diegmann, J.; Pilz, M.; Bachmann, M.; Minich, W.B.; Schomburg, L. Selenium Deficiency Is Associated with Mortality Risk from COVID-19. Nutrients 2020, 12, 2098.

[4] Yu MW, Horng IS, Hsu KH, Chiang YC, Liaw YF, Chen CJ. Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection. Am J Epidemiol. 1999;150(4):367-374. doi:10.1093/oxfordjournals.aje.a010016

[5] Wang, Y., Xie, D., Li, J. et al. Association between dietary selenium intake and the prevalence of osteoporosis: a cross-sectional study. BMC Musculoskelet Disord 20, 585 (2019). https://doi.org/10.1186/s12891-019-2958-5

[6] Bermano, G., Méplan, C., Mercer, D., & Hesketh, J. (2020). Selenium and viral infection: Are there lessons for COVID-19? British Journal of Nutrition, 1-37. doi:10.1017/S0007114520003128
https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/selenium-and-viral-infection-are-there-lessons-for-covid19/BE3AC78D5C92725BE83C4E474ECBB548

[7] Hidalgo AA, Deeb KK, Pike JW, Johnson CS, Trump DL. Dexamethasone enhances 1alpha,25-dihydroxyvitamin D3 effects by increasing vitamin D receptor transcription. J Biol Chem. 2011;286(42):36228-36237. doi:10.1074/jbc.M111.244061

[8] Schütze N, Fritsche J, Ebert-Dümig R, et al. The selenoprotein thioredoxin reductase is expressed in peripheral blood monocytes and THP1 human myeloid leukemia cells--regulation by 1,25-dihydroxyvitamin D3 and selenite. Biofactors. 1999;10(4):329-338. doi:10.1002/biof.5520100403

[9] Martín Giménez, V.M., Inserra, F., Ferder, L. et al. Vitamin D deficiency in African Americans is associated with a high risk of severe disease and mortality by SARS-CoV-2. J Hum Hypertens (2020). https://doi.org/10.1038/s41371-020-00398-z

[10] Wang, Y et al. SARS-CoV-2 suppresses mRNA expression of selenoproteins associated with ferroptosis, ER stress and DNA synthesis. Preprint, 2020/07/31. 10.1101/2020.07.31.230243
https://www.researchgate.net/publication/343365020_SARS-CoV-2_suppresses_mRNA_expression_of_selenoproteins_associated_with_ferroptosis_ER_stress_and_DNA_synthesis

[11] Steinbrenner H, Al-Quraishy S, Dkhil MA, Wunderlich F, Sies H. Dietary selenium in adjuvant therapy of viral and bacterial infections. Adv Nutr. 2015;6(1):73-82. Published 2015 Jan 15. doi:10.3945/an.114.007575

[12] Rayman MP, Winther KH, Pastor-Barriuso R, et al. Effect of long-term selenium supplementation on mortality: Results from a multiple-dose, randomised controlled trial. Free Radic Biol Med. 2018;127:46-54. doi:10.1016/j.freeradbiomed.2018.02.015

[13] Zhao Y, Yang M, Mao Z, et al. The clinical outcomes of selenium supplementation on critically ill patients: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2019;98(20):e15473. doi:10.1097/MD.0000000000015473

[14] Manzanares W, Lemieux M, Elke G, Langlois PL, Bloos F, Heyland DK. High-dose intravenous selenium does not improve clinical outcomes in the critically ill: a systematic review and meta-analysis. Crit Care. 2016;20(1):356. Published 2016 Oct 28. doi:10.1186/s13054-016-1529-5

[15] Angelica Kuria, Hongdou Tian, Mei Li, Yinhe Wang, Jan Olav Aaseth, Jiajie Zang & Yang Cao (2020) Selenium status in the body and cardiovascular disease: a systematic review and meta-analysis, Critical Reviews in Food Science and Nutrition, DOI: 10.1080/10408398.2020.1803200  https://www.tandfonline.com/doi/full/10.1080/10408398.2020.1803200

[16] Thomson CD, Chisholm A, McLachlan SK, Campbell JM. Brazil nuts: an effective way to improve selenium status. Am J Clin Nutr. 2008;87(2):379-384. doi:10.1093/ajcn/87.2.379
https://academic.oup.com/ajcn/article/87/2/379/4633360

[17] Kieliszek M, Lipinski B. Selenium supplementation in the prevention of coronavirus infections (COVID-19) [published online ahead of print, 2020 May 24]. Med Hypotheses. 2020;143:109878. doi:10.1016/j.mehy.2020.109878
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246001/

[18] Im, JH et al. Nutritional status of patients with coronavirus disease 2019 (COVID-19) Int J Infectious Diseases, August 11, 2020
https://www.ijidonline.com/article/S1201-9712(20)30647-0/fulltext

[19] Majeed, M et al. An Exploratory Study of Selenium Status in Normal Subjects and COVID-19 Patients in South Indian population: Case for Adequate Selenium Status: Selenium Status in COVID-19 Patients. Nutrition. Available online 11 November 2020, 111053
https://www.sciencedirect.com/science/article/pii/S0899900720303361

[20] 
Chen Dun, Christi M. Walsh, Sunjae Bae, Amesh Adalja, Eric Toner, Timothy A. Lash, Farah Hashim, Joseph Paturzo, Dorry L. Segev, Martin A. Makary. A Machine Learning Study of 534,023 Medicare Beneficiaries with COVID-19: Implications for Personalized Risk Prediction.
medRxiv 2020.10.27.20220970; doi: https://doi.org/10.1101/2020.10.27.20220970

[21] Delesderrier E, Cople-Rodrigues CS, Omena J, et al. Selenium Status and Hemolysis in Sickle Cell Disease Patients. Nutrients. 2019;11(9):2211. Published 2019 Sep 13. doi:10.3390/nu11092211

[22] Raban Arved Heller, Qian Sun, Julian Hackler, Julian Seelig, Linda Seibert, Asan Cherkezov, Waldemar B. Minich, Petra Seemann, Joachim Diegmann, Maximilian Pilz, Manuel Bachmann, Alireza Ranjbar, Arash Moghaddam, Lutz Schomburg,
Prediction of survival odds in COVID-19 by zinc, age and selenoprotein P as composite biomarker, Redox Biology, Volume 38, 2021101764,

[23] Skalny AV, Timashev PS, Aschner M, et al. Serum Zinc, Copper, and Other Biometals Are Associated with COVID-19 Severity Markers. Metabolites. 2021;11(4):244. Published 2021 Apr 15. doi:10.3390/metabo11040244
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071197/

[24] Zhang, HY., Zhang, AR., Lu, QB. et al. Association between fatality rate of COVID-19 and selenium deficiency in China. BMC Infect Dis 21, 452 (2021). https://doi.org/10.1186/s12879-021-06167-8

[25] Liu Q, Zhao X, Ma J, et al. Selenium (Se) plays a key role in the biological effects of some viruses: Implications for COVID-19. Environ Res. 2021;196:110984. doi:10.1016/j.envres.2021.110984
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937041/

[26] Fakhrolmobasheri, M., Mazaheri-Tehrani, S., Kieliszek, M. et al. COVID-19 and Selenium Deficiency: a Systematic Review. Biol Trace Elem Res (2021). https://doi.org/10.1007/s12011-021-02997-4
https://link.springer.com/article/10.1007/s12011-021-02997-4

[27] Notz, Q.; Herrmann, J.; Schlesinger, T.; Helmer, P.; Sudowe, S.; Sun, Q.; Hackler, J.; Roeder, D.; Lotz, C.; Meybohm, P.; Kranke, P.; Schomburg, L.; Stoppe, C. Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS. Nutrients 2021, 13, 2113.
https://doi.org/10.3390/nu13062113

[28]  Zelija Velija Asimi, Almira Hadzovic-Dzuvo, & Djinan Al Tawil. Selenium, zinc, and vitamin D supplementation affect the clinical course of COVID-19 infection in Hashimoto’s thyroiditis. Presented ePosters 14: COVID-19 Endocrine Abstracts (2021) 73 PEP14.2 | DOI: 10.1530/endoabs.73.PEP14.2
https://www.endocrine-abstracts.org/ea/0073/ea0073pep14.2

[29] Muhammed Majeed, Kalyanam Nagabhushanam, Kalpesh Shah, Lakshmi Mundkur, "A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of a Nutritional Supplement (ImmuActiveTM) for COVID-19 Patients", Evidence-Based Complementary and Alternative Medicine, vol. 2021, Article ID 8447545, 9 pages, 2021. https://doi.org/10.1155/2021/8447545


Friday, 30 July 2021

Virta Health vs Seidelmann - of ketones and COVID-19

You would have seen this paper; senior author is Sara Seidelmann of the infamous "low carb kills" paper, the reviewers were one vegan propagandist David Jenkins (a friend of the family, so to speak) and an Iranian prof with a decent publications list in the plant-based area - neither with any infectious diseases expertise.

There were 568 COVID-19 cases and 2316 controls. Among the 568 cases, 138 individuals had moderate-to-severe COVID-19 severity whereas 430 individuals had very mild to mild COVID-19 severity. After adjusting for important confounders, participants who reported following ‘plant-based diets’ and ‘plant-based diets or pescatarian diets’ had 73% (OR 0.27, 95% CI 0.10 to 0.81) and 59% (OR 0.41, 95% CI 0.17 to 0.99) lower odds of moderate-to-severe COVID-19 severity, respectively, compared with participants who did not follow these diets. Compared with participants who reported following ‘plant-based diets’, those who reported following ‘low carbohydrate, high protein diets’ had greater odds of moderate-to-severe COVID-19 (OR 3.86, 95% CI 1.13 to 13.24). No association was observed between self-reported diets and COVID-19 infection or duration.

you'll find good criticisms in the rapid responses attached, and my PubPeer comment here.

 The methods state 
Lastly, we combined ‘low carbohydrate’ diets and ‘high protein’ diets into another category (‘low carbohydrate, high protein diet’, n=483) to evaluate whether these dietary patterns are associated with COVID-19 severity.

Why? No reason is given for combining these 2 categories. 

There was a keto option, so why didn't they add keto + low carb?

Methods state
Before analyses, we selected dietary patterns with sufficient ‘yes’ responses (‘yes’ response of at least 100 individuals). To increase precision, we analysed three dietary patterns after combining dietary patterns that are similar in terms of dietary intake.

Perhaps keto had less that 100 responses? But there was no registered protocol, those decisions were post-hoc - even if keto had fewer than 100 responses, adding it would have still increased numerical power, which was presumably the point of combining categories as they did. And there's nowhere it says how many responses, and we also have no way of knowing how similar low carb and high protein really were (everything was pretty similar really, these were for most respondents just the virtue-signaling labels they gave to their eating habits).

Anyway, there was no association once people with a negative or no PCR test were excluded.
That's not in the abstract.

But, you know, people are using the keto and LCHF diets to treat diabetes and reduce COVID19 mortality associated with type 2 diabetes, MetSyn, or obesity, so this is a nasty thing to say if it's not true. It's a bit like trying to get people to stop taking vaccines based on your bias and some shit you didn't understand.

Fortunately Vitra Health have ridden to the rescue with a survey of their own T2D population on a ketogenic diet. We know these people are actually following the diet, or adhering closely to it.



The abstract (presented at an ADA conference) is 
COVID-19 Severity in a Geographically Diverse, U.S.-based, Ambulatory Population with Type 2 Diabetes on a Medically Supervised Ketogenic Diet

Data were obtained from medical records and from surveys sent to T2D patients who self-reported COVID-19 diagnosis; 47.8% (294/614) responses and one known COVID-related death yielded a sample of 295 (50% male, 54±9 years, across 41 US states). We observed low reported rates of hospitalization (10.9%), ventilation (2.0%), and death (0.3%) relative to national reports.
Let's compare with the Seidelmann paper - 1) we know the diet is real. 2) COVID-19 is self-reported (some will have tests some not, as in Seidelmann) but - we do have people being hospitalised, unlike Seidelmann, and we even have one death, so Virta are able to capture events that people weren't able to report directly, because their model includes liaison with primary providers likely to report deaths to them. 3) the event rates are low for a population with type 2 diabetes, as shown by the comparison with this population. The populations, though much the same age, aren't identical, but the biggest difference seems to long term inclusion in the Virta Health population (note the "baseline" HbA1c data in Virta - before treatment with the ketogenic diet - is similar to the overall HbAic data in the comparator vs standard practice, but many of the Virta Health population have put their T2D in remission. At this stage, we have to say that the EFFECTS of the keto program are protective - weightloss and euglycaemia, etc. We don't have evidence that keto per se is protective apart from those factors. But that may well be hidden in the data, once the whole set is fully written up. But once again, it looks like Harvard is a bad actor, an ill informant in the nutrition-and-health space, interfering with effective treatments to preserve its own ill-gotten (by a process of bloviation if not graft) dietary hegemony.


Wednesday, 7 July 2021

The Carb-Fat Food Quality Gradient - a real metabolic advantage

This post was originally published as a subscriber-only post on Patreon. You don't have encourage the speculations of the likes of me, but if you want to try, please subscribe!



By now, we've all seen them - studies that purport to show equivalent effects of LCHF and HCLF diets once diet quality is addressed and people are Eating Whole Unprocessed Foods.
The latter is a good thing, the default to go for in terms of population health; macronutrient tweaking is next-level.
But here's a question - why were almost all the original studies that validated the efficacy of LCHF diets to a skeptical medical world comparisons of ad lib low carb vs energy-restricted low fat?
To make a really low carb high fat diet (unless you want to pretend a high-protein diet is that) you're going to be using some isolated fats (cream) or refined ones (coconut oil, olive oil). There may not be sugar in your chocolate bar, but there will be cocoa butter.
This only works if in some way those isolated fats are NOT equivalent to sugar and flour.
What is the evidence for a difference?

One of the more lasting concepts in carb nutrition is the glycemic index, the average speed at which a food appears as glucose in the system. It's not perfect because sugar is only half glucose so is lower GI, but you get the idea.
High GI is worse for you.

The PURE study is good for producing null results, which makes whatever it does throw up seem a bit more reliable than most nutritional epidemiology.[1]

"In the study population, 8780 deaths and 8252 major cardiovascular events occurred during the follow-up period. After performing extensive adjustments comparing the lowest and highest glycemic-index quintiles, we found that a diet with a high glycemic index was associated with an increased risk of a major cardiovascular event or death, both among participants with preexisting cardiovascular disease (hazard ratio, 1.51; 95% confidence interval [CI], 1.25 to 1.82) and among those without such disease (hazard ratio, 1.21; 95% CI, 1.11 to 1.34). Among the components of the primary outcome, a high glycemic index was also associated with an increased risk of death from cardiovascular causes. The results with respect to glycemic load were similar to the findings regarding the glycemic index among the participants with cardiovascular disease at baseline, but the association was not significant among those without preexisting cardiovascular disease."

As I've said before, everything in plants that is supposed to be good for you but isn't actually a real nutrient is probably lowering GI in some way. It's the glucose (glycemic load above) but the way it arrives in your bloodstream (GI) is more pointed.

Is there equivalency for fats? Do fats that are rapidly absorbed correlate with disease?
That would be the medium chain fatty acids, MCFA.

"In comparison to triglycerides containing LCFAs, those containing MCFAs are more rapidly hydrolyzed in the intestinal tract and do not become incorporated into chylomicrons. SCFAs and MCFAs are transported by portal bloodstream to the liver, where they are readily metabolized."[2]

And perhaps also the unsaturated fatty acids, UFA.

"Although pancreatic lipase hydrolyzes fat only in the 1 and 3 positions of the molecule, it is nevertheless possible for fatty acids in the 2 position of the triacylglycerol to be hydrolyzed. This apparent violation of the specificity of pancreatic lipase occurs because of the relative instability of both the 2-monoacylglycerol and the 1,2-diacylglycerol (Crossley et al., 1959). These molecules rearrange by migration of the fatty acid in the 2 position to the 1 or 3 position, which is readily hydrolyzed by lipase (Figure 18–3). This rearrangement is more rapid when the fatty acid is either a short-chain one or an unsaturated one, and a portion of the 2-position fatty acids may be absorbed as fatty acids rather than as monoacylglycerols (Benzonana et al., 1964)."[3]

We'll call this the fat index, FI.
Are fatty acids with a high FI worse than low-FI fats?
No.
In epidemiological studies of individual fatty acids and their associations with disease risk, the MCFAs, which are SFAs, are always more benign than the longer-chain SFAs (see table 2).[4]

"Two recent studies from the Netherlands reported largely diverging findings. In the European Prospective Investigation into Cancer and Nutrition study, intakes of 4:0-10:0 and 12:0 were inversely associated with ischemic heart disease risk, but no associations were found for 14:0, 16:0, and 18:0. However, in the Rotterdam study, only 16:0 intake was associated with higher risk of coronary heart disease." [see also table 2]

In an overfeeding experiment, the benefits of MCFA were obvious.[5]

"In conclusion, substitution of a small amount of dietary LCFAs with MCFAs rescues insulin action in conditions of lipid-induced energy excess."

This is because high-FI fatty acids are metabolized more rapidly, and, in the case of MCFAs, oxidized with less metabolic and hormonal effort than LCFA.[2,6]


In conclusion - if you eat carbs in bulk you will need to pay some attention to the speed at which your body absorbs them; this rules out eating purified carbohydrates.

If you eat fats in bulk, you need pay little attention to the speed your body absorbs them; you may want more fast-absorbing fatty acids in your food, but this does not rule out eating purified fats.

[1] Jenkins DJA, Dehghan M, Mente A, Bangdiwala SI, Rangarajan S, Srichaikul K, Mohan V, Avezum A, Díaz R, Rosengren A, Lanas F, Lopez-Jaramillo P, Li W, Oguz A, Khatib R, Poirier P, Mohammadifard N, Pepe A, Alhabib KF, Chifamba J, Yusufali AH, Iqbal R, Yeates K, Yusoff K, Ismail N, Teo K, Swaminathan S, Liu X, Zatońska K, Yusuf R, Yusuf S; PURE Study Investigators. Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality. N Engl J Med. 2021 Apr 8;384(14):1312-1322. doi: 10.1056/NEJMoa2007123. Epub 2021 Feb 24. PMID: 33626252.
https://www.nejm.org/doi/full/10.1056/NEJMoa2007123

[2] Schönfeld P, Wojtczak L. Short- and medium-chain fatty acids in energy metabolism: the cellular perspective. J Lipid Res. 2016;57(6):943-954. doi:10.1194/jlr.R067629
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878196/

[3] Institute of Medicine (US) Committee on Military Nutrition Research; Marriott BM, editor. Food Components to Enhance Performance: An Evaluation of Potential Performance-Enhancing Food Components for Operational Rations. Washington (DC): National Academies Press (US); 1994. 18, Structured Lipids: An Overview and Comments on Performance Enhancement Potential. Available from: https://www.ncbi.nlm.nih.gov/books/NBK209064/

[4] Zong G, Li Y, Wanders A J, Alssema M, Zock P L, Willett W C et al. Intake of individual saturated fatty acids and risk of coronary heart disease in US men and women: two prospective longitudinal cohort studies BMJ 2016; 355 :i5796 doi:10.1136/bmj.i5796
https://www.bmj.com/content/355/bmj.i5796

[5] Anne-Marie Lundsgaard, Andreas M. Fritzen, Kim A. Sjøberg, Maximilian Kleinert, Erik A. Richter, Bente Kiens. Small Amounts of Dietary Medium-Chain Fatty Acids Protect Against Insulin Resistance During Caloric Excess in Humans.
Diabetes Jan 2021, 70 (1) 91-98; DOI: 10.2337/db20-0582
https://diabetes.diabetesjournals.org/content/70/1/91

[6] James P DeLany, Marlene M Windhauser, Catherine M Champagne, George A Bray, Differential oxidation of individual dietary fatty acids in humans, The American Journal of Clinical Nutrition, Volume 72, Issue 4, October 2000, Pages 905–911, https://doi.org/10.1093/ajcn/72.4.905

Sunday, 27 June 2021

Probiotic extracts for PTSD - proof of concept for the gut-brain axis?

It is with great pleasure that I can announce results from an experiment I was actually involved with, albeit long ago.

It happened like this - having noticed that probiotics were helping with my HCV symptoms, I was theorising about the reasons for this in a Hep C forum with nurse Silvia H, who supplied a lot of my early background on immunity; this attracted the notice of Elizabeth McKenna, who was working with Beth Jones, the senior author of the present paper. Dr Jones had invented a process for producing a cell wall lysate from bacteria that, or so it was claimed, preserved the probiotic immune function to a far greater extent than other lysates and heat-killed probiotic products then available.

I knew a bit about these products because a friend with HCV swore by a product called Del Immune V, which had corrected what seemed to be autoimmune symptoms. I tried this product but to be honest was already so saturated with effective herbs and other supps that I couldn't honestly say what it did, though it did appear to be something. But by looking on the interwebs, as they then were, I could deduce a bit about such things. 

My theory was, still is, that commensal bacteria - as well as herbs like astragalus and some mushroom sp. produce polysaccharides and other PAMP signaling molecules that mimic LPS in a benign way. An agonist-antagonist relationship with PAMP receptors could explain this modified version of the effect (this is why it can be useful having a druggie on the board, pharma execs). This summary minimizes the amount of reading I did on complement and alternative complement pathways, Tregs and Th17, retinoid metabolism and immune cell differentiation, dendrite cell translocation of LPS, and other things that mercifully I only faintly remember now. Anyway, it looked as if the toll-like receptors, a major PAMP recognition pathway, were important.

Elizabeth McKenna, by now the CEO of Labyrinth holdings overseeing the patent process for Dr Jones, had the realization that TLR activity was assayable - the tests were done and, as in the current paper, there was significant activity at several PAMP receptors.

Soon after I received some test samples of the product, now called ReseT. From Reset T cells - a good concept but as it turned out a very poor name when it came to finding the product in search engines!

Anyway, at the time I still had HCV, and that was one possible use for ReseT, so I thought I should try it. Even though at the time my symptoms were under control and I had no idea if I would notice, because that's how I roll, someone has to try things and I was already implicated, as it were.

We know know that the dose I took was about twice what's optimal. It's a sublingual lactose-based pill, or was, and the effect was rapid. The pattern on the carpet in front of me softened, life softened, and I felt something very similar to the effect of valium or some other GABA agonist. Well that's quite impressive I thought, but it left me fully functional and I was on my way to a Neil Young concert.
While on the way I smoked a couple of strong joints.
Then there I was, trapped indoors with thousands of strangers in a swirling mob. 
This sort of thing is of course a recipe for social anxiety, and it's normal to negotiate this effect, which can get quite harsh, if you're a stoner who wants to be really stoned for, you know, NEIL.

But this time things were completely different - I was immune to anxiety. And I remained immune to anxiety from this cause for a long time after I stopped taking ReseT, which I didn't take regularly for long, and it's never really been all that strong ever again.

Now, the experiential effects I've described haven't been described by anyone else - that is, no-one else who's benefitted from ReseT since seems to have observed the point at which it happened in the way I did. That's Okay, I'm used to being highly observant of such things, even though it gets me laughed at sometimes. I only noticed the strong GABA effects on the first two or three occasions I took ReseT, fading as I became less prone to anxiety.

Anyway I drifted away from the probiotic problem as other work came along, and though Elizabeth McKenna kept in touch I did think the proposed mechanism, that the effect can be explained by the manipulation of oxidative stress, was putting too much onus on the immune system. and too much responsibility on bacteria.

But obviously I didn't have all the facts that the people on the ground did, and as it happens there's nothing better than a highly simplistic hypothesis - IF the evidence supports it.
If the evidence supports a simple explanation, there is no immediate requirement for terms like complex and multifactorial. To paraphrase William of Occam.

In the first of two papers, A pilot study: Innate immune modulation reduces F2-Isoprostanes and improves psychological health in a chronically stressed cohort 
https://onlinelibrary.wiley.com/doi/10.1002/hsr2.289

Seven male participants (combat veterans aged between 28 and 47 years) with PTSD completed the 70-day study.

The study design was a single-arm treatment study, wherein the effects of treatment were assessed and compared to the baseline pretreatment values (Day 1). Once the baseline samples were collected, the study participants were requested to take two 12 mg tablets, sublingually, twice daily (48 mg daily dose) for the duration of the study, and maintain their normal daily routine. Treatment sample collection and the measurements were performed on Days 15 and 70.



The graphs demonstrate after 14 days of treatment, most of the participants experienced improved psychological health that were consistent with reduced urinary levels of F2-IsoP (Figure 1A). In case of depression profiles, there was significant improvement observed by Day 15 (Figure 1D). However, with further treatment, the participants continued to exhibit improvement, with significant improvement in the metrics of life satisfaction (Figure 1B) and daytime sleepiness (Figure 1C) by Day 70. The correlation coefficients between the F2-IsoP and mental health parameter values were −0.99, 0.99, 0.95, and 0.96 for life satisfaction, sleepiness, depression, and anxiety, respectively.

To be sure, the study wasn't controlled. But a placebo effect shouldn't lower F2-IsoP that much, and I think it very unlikely that placebo effects can be maintained this consistently for 55 days, especially given the very minimal interaction between participants and clinicians during the study. But note that the antianxiety effect I noticed is probably only being experienced by one or two participants.

Anyway, placebos shouldn't affect drosophila, and there's also a fruit fly study that corroborates that ReseT is bioactive (via NF-κβ).

Treatment with Bacterial Biologics Promotes Healthy Aging and Traumatic Brain Injury Responses in Adult Drosophila, Modeling the Gut–Brain Axis and Inflammation Responses
https://www.mdpi.com/2073-4409/10/4/900

Here we get to compare ReseT with a well-tested live bacteria that is closely related to its source, LGG.

Here, we examine the response of adult Drosophila given an inactive bacteriologic (IAB; proprietary lysate preparation of Lactobacillus bulgaricus, ReseT®) and a probiotic (Lactobacillus rhamnosus, LGG). In vitro, the IAB activates a subset of conserved Toll-like receptor (TLR) and nucleotide-binding, oligomerization domain-containing protein (NOD) receptors in human cells, and oral administration slowed the age-related decline of adult Drosophila locomotor behaviors. On average, IAB-treated flies lived significantly longer (+23%) and had lower neural aggregate profiles. Different IAB dosages also improved locomotor function and longevity profiles after traumatic brain injury (TBI) exposure. Mechanistically, short-term IAB and LGG treatment altered baseline nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ) signaling profiles in neural and abdominal tissues. Overall, at select dosages, IAB and LGG exposure has a positive impact on Drosophila longevity, neural aging, and mild traumatic brain injury (TBI)-related responses, with IAB showing greater benefit. This includes severe TBI (sTBI) responses, where IAB treatment was protective and LGG increased acute mortality profiles. 

Well. Interestingly there may be a "too much" point here with both interventions where they are no longer great, with a lower tolerance for the live probiotic. These are not placebos.  



Anyway L. Bulgaricus was the probiotic that Élie Metchnikoff predicted would extend life in 1907.

Just sayin'.

Tolstoy and Metchnikoff, 

Disclaimer - my work for Labyrinth in its early days was pro bono, and I've never been paid by anyone involved. I did receive two textbooks.