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Tuesday, 23 August 2022
Selenium reduces COVID-19 risk - a back-of-the-envelope Bradford Hill analysis [originally posted 28/09/20, last updated 13/06/22]
Remember, a long time has passed and a lot of people have died while Evidence-Based Medicine was facing the wrong way.
Selenium reduces COVID-19 mortality: A Bradford Hill analysis
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.
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.
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.
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.
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).
See also refs 19 and 22, discussed below.
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 13/06/2022] - New study from the USA shows a two-fold higher mortality rate in low-selenium regions.
Discussed in more detail on my Patreon blog - the only way I make any part of a living from this work, so help a brother out!
[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.
[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."
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.
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.
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. In the German study, the temporal association between low serum selenium levels and COVID-19 symptom severity was closely tracked.
5) Dose-response gradient - Very Strong
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. 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.
Selenium sufficiency is essential for the function of vitamin D in peripheral blood monocytes. Vitamin D status also correlates with COVID-19 survival.
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.
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.
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.
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:
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.
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. Pity the low dose arms here weren't retained in the intervention.
During 6871 person-years of follow-up, 158 deaths occurred. In an intention-to-treat analysis
[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.
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.
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]
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.
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.
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:
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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.
 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
 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
 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
 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
 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.
 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
 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
 JinsongZhanga, EthanWill Taylorb, KateBennett, Margaret P. Rayman. Does atmospheric dimethyldiselenide play a role in reducing COVID-19 mortality?
Tuesday, 24 May 2022
New Zealand schools have introduced a climate change resource that suggests children “eat less meat and dairy”, even though teachers will not know how much meat or dairy any child in their care has eaten. Opinion pieces in the papers have called for the reduction of meat and dairy in hospital menus, not usually generous sources of such foods, despite the well-known risks of undernutrition, especially of protein, in the frail and elderly. Globally, the influential and once-objective medical journal the Lancet has hosted Eat Lancet, a coalition of vegan and vegetarian technocrats backed by processed food manufacturers, and promoted their agenda. The Guardian newspaper accepted an $886,600 grant from the backers of Impossible Foods to run a series of articles against animal agriculture.
These initiatives, aimed at remodelling our food supply in a way that favours the multinational food processing and seed-and-chemical corporations, whose control of many aspects of farming and diet is already problematic, have run far ahead of the scientific community’s efforts to understand the health effects of such dietary change.
Our hunter-gatherer past
The Neolithic Revolution was the first alteration in human affairs that is generally considered worthy of the term Revolution. In Marx’s terms, it saw a change in the means of production sufficient to form new classes aware of their identities, and thus a change in the relations between people. Early humans had fed themselves in an opportunistic, hunter-gatherer fashion that tended to favour a diet of animals supplemented with plants where and when these were available. Large animals made the best meals but gathering activities could collect many smaller ones, as well as eggs, grubs etc.
The people of the Mesolithic era discovered that some animals could be herded and some plants grown in gardens (not usually by the same community, because one activity favours nomadism and the other favours a sedentary habit) but these activities, which greatly improved food security after the decline of the prehistoric mega-fauna due to hunting and climate pressures, tended to occur at the communal level and probably did not create major class differences between the people involved.
The invention of farming
The Neolithic Revolution, which unleashed the human potential for war, creativity, and social division, resulted from the identification of the germs of plants (specifically grains and legumes) as durable sources of energy. If grains were grown (I will use grains in the wider sense of “cereals”, after Braudel, including other dried germs such as peas) and there was a surplus, this surplus would still be edible over the next year, a year when drought or pests or diseases might wipe out the other food sources that hunter-gatherers depended on. This advantage was offset by the nutritional poverty of grain-based diets, so that tuberculosis probably became an endemic disease during this period, but the existence of a less-perishable surplus allowed the diversion of part of the population away from food gathering for large parts of the year, and saw the creation of armies and other workforces.
In Europe, the Neolithic Revolution is dated at around 10,000 BC and its arrangements are a matter of prehistory, but in China this change occurred later and the written record around Bi-gu or grain avoidance includes folk-memories of conflict between grain eating and grain avoiding peoples.
The history of colonisation is the history of the conquest of lactose-intolerant peoples by lactose-tolerant populations, and of non-grain eaters by grain-eaters. In the Indian sub-continent, a combination of dairy herding and a cereal diet high in legumes uniquely allowed the survival of a substantially vegetarian population, and saw the conservation of genes favouring reproduction on such a diet, including genetic polymorphisms still rare in European populations (adaptive mutations only predominate where many individuals without them have failed to survive or reproduce). That the Indian social system became more aggressively class-based than any other is probably no co-incidence; prejudice against meat-eating is still used as a tool of social control against minorities, while meat-eating is one way young Indians today identify as modern and egalitarian. However there were some important exceptions to the trend – the Aztecs were a hunter-gather people who conquered and dominated the Mesolithic agriculturalists of Mexico, and the Mongols were nomadic herders and hunters whose greater stamina and independence allowed them to defeat the rice-fed armies of the Chinese Emperors (after conquering this breadbasket, the successive Mongol Khans seem to have eaten and drunk themselves to death).
Early vegetarian ideology
In the European and Asian cereal-based societies the poorest classes went without meat, supplementing cereals when possible with buttermilk or blood pudding which were more economic replacements. The rich ate as much meat as they could. The idea that an entire society might avoid meat is a recent one with its roots in religious practice, and, insofar as it has any political basis, this flows in two distinct streams – the eco-fascist, in which meat avoidance is a sign of “purity”, most humans are a burden on the Earth, and the Indian vegetarians are of course Aryans. This is something like the vegetarian vision that Adolf Hitler picked up while studying anti-Semitism with Wagner’s heirs at Bayreuth.
And then there is a Marxist-Anarchist, and latterly Intersectional, version, founded on a valuation of animal rights as inseparable from, and a logical extension of, human rights. Vegetarianism was a frequent obsession of the early British Socialists; G.B. Shaw, who derived most of his energy from dairy fat and lived to the age of 94, made himself into a well-known example, and the idea was sufficiently entrenched among the British Socialists and their milieu that H.G. Wells preserved its internal contradictions for posterity in The Time Machine. In his far-future vision, humanity has evolved into two separate species. The Morlocks are descendants of working-class meat-eaters, the Eloi of leisure-class vegetarians – all Wells’ loathing is reserved for the Morlocks, yet it is obvious they are (still) the engineering brains keeping their world running and the Eloi fed. The Eloi are useless for anything but enjoying the sunshine and feeding the Morlocks, and the discordance in Wells’ progressive values as he describes both species is as shocking as anything else in the story. "But gradually the truth dawned on me: that Man had not remained one species, but had differentiated into two distinct animals: that my graceful children of the Upper-world were not the sole descendants of our generation, but that this bleached, obscene, nocturnal Thing, which had flashed before me, was also heir to all the ages."
The first large-scale experiment in plant-based protein was attempted by the Bolsheviks. As usual, it’s hard to separate the roles played by idealism and cynicism in the story, but the bare bones are that the Soviets found their initial attempts to remodel the countryside rebuffed, blamed this on the recaltricance of the kulak class, and set out to destroy them. The problem being that the kulaks, owning most of the cattle and sheep across the Russian Republics, helped to feed the people. Beginning in the 1920s, soy experts from the USA (then the Western world’s leading soy producer) were among the many foreign technicians imported into Russia, and soy processing plants were built and soy production increased to 283,000 tonnes in 1931, the year Stalin unleashed enforced collectivisation and the terror against the kulaks (and also the Kazakhs, a herding people who suffered the largest proportionate loss of life during this period). This led to the loss of millions of animals, either killed by their dispossessed owners or mismanaged by their inexperienced new owners. The soy project was hardly able to prevent the massive famines that followed, and by 1935 soy production had dropped to 54,000 tonnes. Though soy milk would later prove useful during the siege of Leningrad, by the 1930s soy had probably only served one purpose, as a statistic needed aforehand to quell the objections of pragmatic delegates to the destruction of the kulaks and their livestock.
Today we face the revival of this idea, of plant protein that will create a world with no need for animal protein, and the remodelling of life in the countryside, with the new impetus of climate change as its driver. Livestock cycles natural carbon, meaning there is no net addition of C02 to the atmosphere – and its contribution to the shorter-lived methane precursor has not changed since 2000 (methane rises have been due to fracking, methane itself AKA “natural gas”, landfill, and rice production; methane-emitting animals have always existed on Earth in substantial numbers, and have not created a novel situation in the sense that the discovery of coal, oil and gas did). We have recently seen how much global disruption is required to reduce fossil fuel CO2 emissions to 2006 levels, levels which will still warm the planet if they continue. It could be still be worth reducing agricultural cycling of CO2 through methane, which is more warming than CO2 if this is cost-free, but is it?
Why humans evolved as meat eaters
Animal foods, and especially red meat, supply a constellation of nutrients not found together (if they are found at all) in any plant food. Nutrients are those chemicals essential for the functioning of the human organism, and plants, but not livestock, can survive well without nutrients such as amino acids, fatty acids, vitamins and minerals that are essential to humans. Surviving as a vegetarian or vegan is possible for some (perhaps assuming the genetic variants referred to earlier are present) but to thrive requires knowledge of these nutrients, where to find them, how to process the foods that supply them, or how to supplement them. Thriving as an omnivore or even a complete carnivore does not – nutritional sufficiency is the reason we evolved eating meat and other animal foods long before we learned there were such things as essential nutrients.
The reasons for avoiding meat or all animal foods can have a class basis – veganism may be taken up by educated middle-class adults, more likely to be exposed to “health food” ideas and aware of the need to supplement, some of whom then commercialise their habits as social media “influencers”. Meat avoidance is also being adopted increasingly by educated middle-class children for identity or compassionate reasons, but the poor may also avoid meat because of its cost when a loaf of bread or a packet of flavoured noodles can be bought for a dollar; these two motivations sometimes coincide when students in temporary poverty make a virtue of what they perceive to be a necessity.
Does the meat-avoiding behaviour of young people have unintended costs? Several observational studies have looked at the characteristics of meat-avoiding populations and found alarming increases in depression, anxiety and self-harm.
“The majority of studies, and especially the higher quality studies, showed that those who avoided meat consumption had significantly higher rates or risk of depression, anxiety, and/or self-harm behaviors. There was mixed evidence for temporal relations, but study designs and a lack of rigor precluded inferences of causal relations. Our study does not support meat avoidance as a strategy to benefit psychological health.”
How can we explain these correlations? Why should we assume that they are causal? There are several lines of evidence to support a causal link:
1) several nutrients found in meat and animal foods are important factors in mood and cognition; vitamin B12, iron, carnitine, DHA, choline and tryptophan are some examples.
2) the fatty acid mix in dairy and red meat has a similar composition to that of amniotic fluid and breast milk which has anxiolytic (anti-anxiety) effects in young animals.
3) soy is a convenient and cheap replacement for animal protein; soy processing in Western diets results in a 10-fold higher level of the estrogenic contaminant isoflavone than that found in Asian diets. Soy isoflavone causes anxiety behaviour in young female animals, and there is evidence supporting psychotropic and hormonal effects in humans.[7,8,9.10] Interestingly, while right-wing critiques of soy eating focus on effects it can have on young men, the scientific evidence for adverse effects in younger females, converting to HRT-like benefits after menopause, is stronger.
4) other toxins found in plants, such as salicylates and oxalates, as well as problematic proteins such as gliadin/gluten and zein, may be present at higher levels in meat-free diets (but are not unique to them). A vegan mince sold in Countdown supermarkets is simply a coloured blend of soy protein and gluten, a protein linked to the risk of schizophrenia.
In the New Zealand context it would be relatively easy to confirm or dispute some of these associations. Everyone admitted to hospital for longer than a day supplies their dietary preferences. The dietetic preference data from psychiatric admissions could be both linked to outcomes over time and compared with the population average distribution, or the distribution in a ward where diet is least likely to play a role in admissions.
Iron deficiency in women
Young women in New Zealand are the most likely to report being vegan or vegetarian in surveys, as elsewhere in the world. Vegans in the Gender Studies field generate papers linking meat to masculinity, with the implication that this masculinity is toxic and might be improved by a plant-based diet. The corollary of this belief – that women may therefore be weakened by meat-avoidance – is never considered. In a 1980 essay by Gloria Steinem called The Politics of Food (in the collection Outrageous Acts and Everyday Rebellions) she describes some of the cultural constructs by which women are deprived of the good nutrition which men use to stay dominant. The belief that men need to eat red meat more often than women may have been valid when the average man was more likely to have to survive an attack by a wild bear than the average woman, but today it is mainly women who suffer from serious iron deficiency. The rate – and the cost to the health system – is increasing in New Zealand as more women give up meat. Iron deficiency anaemia in early pregnancy is associated with neurodevelopmental disorders in children, not an outcome that will increase the mother’s autonomy.
In Georg Büchner’s 19th century “working class tragedy” Woyzeck, filmed by Werner Herzog with Klaus Kinski in the leading role and the subject of an opera by Alban Berg, the title character, a soldier, is subject to experimentation by a sadistic army doctor. The experiment involves Woyzeck living on nothing but peas. Peas may supply a complete protein, but Woyzeck goes insane; the deprivation being the final straw in his alienation. James Cameron, the film-maker responsible for Avatar and Titanic, is investing heavily in pea protein as if this were his gift to New Zealand. I am not sure whether he has watched Woyzeck – one would think he has.
Plant-based vs meat-based
Again, we have the specificity of plant germs as commodity; their low cost of production, long storage life and versatility of processing outcomes makes them an ideal investment and a robust one, as poverty and adversity increases their consumption, as we saw during the 2020 Lockdown Event. However, a plant-based burger is nutritionally greatly inferior to a meat burger, and that burger is often the most nutritious single food item many will people eat in the course of their day. The current push to eat a plant-based diet for “planetary health” is something that all the multinational food processors have signed up and provided funding for, and why not – Coca Cola, Unilever, Nestlé have always sold us plant-based foods. We notice that while iron-deficiency anaemia increases in New Zealand with the reason in plain sight, Nestlé scientists here in NZ are developing a more potent form of supplemental iron to add value to their products as their parent company backs the push to reduce meat. (As usual, it’s hard to separate the roles played by idealism and cynicism in the story).
But, you may well ask, isn’t eating meat linked to an increased risk of cancer and heart disease? These associations are small to begin with, but they are also intensely confounded by social class and educational status. Supposing a factory that makes a carcinogenic chemical is hiring. Who is more likely to apply for that job – a meat eater (who will likely have a bigger family to support, among other considerations) or a vegan? Who, so to speak, eats all the pies, and needs food that is filling and nutritious without having to give it much thought? Who is more likely to work two jobs and be exposed to the disruptive metabolic effect of shift work? Carcinogen exposure and shift work are just two of the confounding variables ignored in diet epidemiology. (That meat-eating in Western populations may symbolise or associate with labour itself – as it did for H.G. Wells when he wrote The Time Machine – is not a consideration I have found discussed in the epidemiological literature.)
Certainly one can think of mechanisms that might link meat to disease, as one can with any food, but one can also think of protective mechanisms; several of the nutrients found mainly or only in animal foods are required for various antioxidant and immune defensive enzymes, and some like carnitine and EPA even have a place in the management of heart disease.
The argument against meat-eating should not be confused with the argument for sometimes rationing a valuable food that is in short supply. The wartime rationing of meat in the UK is thought to have improved the health of the poorest by guaranteeing a greater supply than they had had previously, at a more affordable price. In Europe, the peasants who supplied the cities with meat, dairy and luxury foods such as oysters were sometimes forced by network disruptions to consume these foods – which many of them had never tasted before – with benefit to their own health.
The plant-based agenda can scarcely be expected to recognise these benefits, or understand the argument summarised by Williams and Dunbar (with regard to the vitamin nicotinamide and amino acid tryptophan in their tuberculosis paper), that if better data collection and analysis resulted in us ”…returning to our egalitarian past and redistributing meat or its components that supply NAD (avoiding both the highs and the lows between individuals and over individual lifetimes) [this] may be more effective than subsidizing corn grain (while the increased prosperity from unlocking human potential should pay for the intervention).”
Progress – which includes unlocking human potential from the chains of preventable mental and physical disease – depends on good data, and we do not yet seem to collate the data required to know whether or for whom plant-based diets are safe in New Zealand.
George Henderson works as a researcher for Professor Grant Schofield and the team behind the What The Fat books and the social enterprise PreKure, which has been running free lifestyle and health programs through the lockdown. He is the author or co-author of several scientific articles and letters published by the BMJ, Lancet Diabetes and Endocrinology, the JAMA, and other journals, including an influential review of low carbohydrate diets in diabetes management for the New Zealand Medical Journal. A musician, songwriter and amateur musicologist, he has recently presented a series of podcasts on 20th century women composers for Karyn Hay’s Lately show on RNZ.
 Williams AC, Dunbar RI. Big brains, meat, tuberculosis, and the nicotinamide switches: co-evolutionary relationships with modern repercussions?. Int J Tryptophan Res. 2013;6:73‐88. Published 2013 Oct 15. doi:10.4137/IJTR.S12838
 Kothapalli KS, Ye K, Gadgil MS, et al. Positive Selection on a Regulatory Insertion-Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid. Mol Biol Evol. 2016;33(7):1726‐1739. doi:10.1093/molbev/msw049
 Urska Dobersek, Gabrielle Wy, Joshua Adkins, Sydney Altmeyer, Kaitlin Krout, Carl J. Lavie & Edward Archer (2020) Meat and mental health: a systematic review of meat abstention and depression, anxiety, and related phenomena, Critical Reviews in Food Science and Nutrition, DOI: 10.1080/10408398.2020.1741505
 Frédéric Leroy & Nathan Cofnas (2019) Should dietary guidelines recommend low red meat intake?, Critical Reviews in Food Science and Nutrition, DOI: 10.1080/10408398.2019.1657063
 Contreras CM, Rodríguez-Landa JF, García-Ríos RI, Cueto-Escobedo J, Guillen-Ruiz G, Bernal-Morales B. Myristic acid produces anxiolytic-like effects in Wistar rats in the elevated plus maze. Biomed Res Int. 2014;2014:492141. doi:10.1155/2014/492141
 Fernandez-Lopez A, Lamothe V, Delample M, Denayrolles M, Bennetau-Pelissero C. Removing isoflavones from modern soyfood: Why and how?. Food Chem. 2016;210:286‐294. doi:10.1016/j.foodchem.2016.04.126
 Hicks KD, Sullivan AW, Cao J, Sluzas E, Rebuli M, Patisaul HB. Interaction of bisphenol A (BPA) and soy phytoestrogens on sexually dimorphic sociosexual behaviors in male and female rats. Horm Behav. 2016;84:121‐126. doi:10.1016/j.yhbeh.2016.06.010
 Tillett T. Full of beans? Early soy exposure associated with less feminine play in girls [published correction appears in Environ Health Perspect. 2012 Jan;120(1):A17]. Environ Health Perspect. 2011;119(12):A525. doi:10.1289/ehp.119-a525b
 Adgent MA, Daniels JL, Rogan WJ, et al. Early-life soy exposure and age at menarche. Paediatr Perinat Epidemiol. 2012;26(2):163‐175. doi:10.1111/j.1365-3016.2011.01244.x
 Hibbeln, J.R., SanGiovanni, J.P., Golding, J., Emmett, P.M., Northstone, K., Davis, J.M., Schuckit, M. and Heron, J. (2017), Meat Consumption During Pregnancy and Substance Misuse Among Adolescent Offspring: Stratification of TCN2 Genetic Variants. Alcohol Clin Exp Res, 41: 1928-1937. doi:10.1111/acer.13494
 Patisaul HB, Jefferson W. The pros and cons of phytoestrogens. Front Neuroendocrinol. 2010;31(4):400‐419. doi:10.1016/j.yfrne.2010.03.003
 Čiháková D, Eaton WW, Talor MV, et al. Gliadin-related antibodies in schizophrenia. Schizophr Res. 2018;195:585‐586. doi:10.1016/j.schres.2017.08.051
 Jessica Greenebaum & Brandon Dexter (2018) Vegan men and hybrid masculinity, Journal of Gender Studies, 27:6, 637-648, DOI: 10.1080/09589236.2017.1287064
 Wiegersma AM, Dalman C, Lee BK, Karlsson H, Gardner RM. Association of Prenatal Maternal Anemia With Neurodevelopmental Disorders. JAMA Psychiatry. 2019;76(12):1294–1304. doi:10.1001/jamapsychiatry.2019.2309
This article originally appeared on the Redliner blog
Sunday, 15 May 2022
Vegan diets and the risk of deficiency
diseases – the story of Shelly
One of the earliest objective accounts of the effects of a vegetarian diet in English is Thomas Love Peacock’s observations of his friend, the poet Percy Bysshe Shelly. I think these are interesting because Shelly’s ordeal is very similar to what enthusiastic young people subject themselves to today, and because Peacock’s dry humour can speak for the rest of us.
Quotes are from Thomas Love Peacock’s Memoir of Percy Bysshe Shelly.
Shelly had come under the influence of JF Newton, author of The Return to Nature, or A Defense of the Vegetable Regimen.
Peacock wrote of Newton “He was an estimable man and an agreeable companion, and he was not the less amusing that he was the absolute impersonation of a single theory, or rather of two single theories rolled into one. He held that all diseases and all aberrations, moral and physical, had their origin in the use of animal food and of fermented and spirituous liquors; that the universal adoption of a diet of roots, fruits, and distilled water, would restore the golden age of universal health, purity, and peace ; that this most ancient and sublime morality was mystically inculcated in the most ancient Zodiac, which was that of Dendera…”[I will spare you Peacock’s lengthy exposition of this astrological system]
“At Bracknell, Shelley was surrounded by a
numerous society, all in a great measure of his own opinions in relation to
religion and politics, and the larger portion of them in relation to vegetable
Shelley had published the treatise, A Vindication of Natural Diet, in 1813.
But Peacock was skeptical of Shelly’s claims to superior health;
His vegetable diet entered for something into his restlessness. When he was fixed in a place he adhered to this diet consistently and conscientiously, but it certainly did not agree with him; it made him weak and nervous, and exaggerated the sensitiveness of his imagination. Then arose those thick - coming fancies which almost invariably preceded his change of place. While he was living from inn to inn he was obliged to live, as he said, ' on what he could get '; that is to say, like other people. When he got well under this process he gave all the credit to locomotion, and held himself to have thus benefited, not in consequence of his change of regimen, but in spite of it. Once, when I was living in the country, I received a note from him wishing me to call on him in London. I did so, and found him ill in bed. He said, ' You are looking well. I suppose you go on in your old way, living on animal food and fermented liquor ?' I answered in the affirmative. ' And here,' he said, ' you see a vegetable feeder overcome by disease.' I said, ' Perhaps the diet is the cause.' This he would by no means allow ; but it was not long before he was again posting through some yet unvisited wilds, and recovering his health as usual, by living ' on what he could get '.
In Edinburgh he became acquainted with a young Brazilian named Baptista, who had gone there to study medicine by his father's desire, and not from any vocation to the science, which he cordially abominated, as being all hypothesis, without the fraction of a basis of certainty to rest on. They corresponded after Shelley left Edinburgh, and subsequently renewed their intimacy in London. He was a frank, warm-hearted, very gentlemanly young man. He was a great enthusiast, and sympathized earnestly in all Shelley's views, even to the adoption of vegetable diet. He made some progress in a translation of Queen Mab into Portuguese. He showed me a sonnet, which he intended to prefix to his translation. It began — Sublime Shelley, cantor di verdade !
and ended — Surja Queen Mab a restaurar o mundo.
I have forgotten the intermediate lines. But he died early, of a disease of the lungs. The climate did not suit him, and he exposed himself to it incautiously.
On our way up, at Oxford, he [Shelly] was so much out of order that he feared being obliged to return. He had been living chiefly on tea and bread and butter, drinking occasionally a sort of spurious lemonade, made of some powder in a box, which, as he was reading at the time the Tale of a Tub, he called the powder of pimperlimpimp. He consulted a doctor, who may have done him some good, but it was not apparent. I told him, If he would allow me to prescribe for him, I would set him to rights." He asked, ‘What would be your prescription ? ' I said, ' Three mutton chops, well peppered/ He said, ' Do you really think so? ' I said, ' I am sure of it." He took the prescription; the success was obvious and immediate. He lived in my way for the rest of our expedition, rowed vigorously, was cheerful, merry, overflowing with animal spirits, and had certainly one week of thorough enjoyment of life.
(There is a confirmation of Peacock’s statement above in a letter Shelly wrote to Hogg in September, 1815, 'on my return from a water excursion on the Thames,' in which Shelley remarks that 'the exercise and dissipation of mind attached to such an expedition have produced so favourable an effect on my health, that my habitual dejection and irritability have almost deserted me.’)
At the time of publishing A Vindication of Natural Diet, Shelly was subject to bizarre hallucinations and phobias, an example of which is given below by Peacock
About the end of 1813, Shelley was troubled by one of his most extraordinary delusions. He fancied that a fat old woman who sat opposite to him in a mail coach was afflicted with elephantiasis, that the disease was infectious and incurable, and that he had caught it from her. He was continually on the watch for its symptoms ; his legs were to swell to the size of an elephant's, and his skin was to be crumpled over like goose-skin. He would draw the skin of his own hands, arms, and neck very tight, and if he discovered any deviation from smoothness, he would seize the person next to him, and endeavour by a corresponding pressure to see if any corresponding deviation existed. He often startled young ladies in an evening party by this singular process, which was as instantaneous as a flash of lightning. His friends took various methods of dispelling the delusion. I quoted to him the words of Lucretius : —
Est elephas morbus, qui propter flumina Nili Gignitur Aegypto in media, neque praelerea usquam. *
He said these verses were the greatest
comfort he had. When he found that, as the days rolled on, his legs retained
their proportion, and his skin its smoothness, the delusion died away.
* the gist of this quote seems to be that elephantiasis is only generated from the waters of the Nile.
Monday, 21 March 2022
I've written in an earlier post about what's wrong with recommending paracetamol to people with Covid. There are no RCTs to show it's safe, and there are undisputed findings from toxicology and Covid-10 pathology which, taken together, suggest a potential for danger,
Paracetamol overdoses used to kill around 200 people a year in New Zealand according to data which was regularly published in the 1970's and 1980's. Today the policy is to censor any information related to suicide. Does this work? On the one hand copy-cat effects are easy to confirm in real life, on the other hand the problem seems to have gotten worse overall under this "hear no evil" policy.
At any rate, deaths due to paracetamol fell sharply when Parvolex (NAC) was introduced as an antidote (which happened much later than it should have, and today the standard treatment seems to be reduced glutathione.
Paracetamol (acetaminophen) metabolises to a free radical, which peroxidises lipids within the liver, causing liver failure. Glutathione, a reduced antioxidant peptide renewed by selenium enzymes, is the primary defense against lipid peroxidation. Lipid peroxidation is how SARS-CoV-2 destroys the lungs. The toxic metabolite is formed by CYP450 E21 enzyme degradation. In animal models, a diet high in polyunsaturated fat (the most peroxidizable fatty acids) and low in protein (the source of glutathione) accelerates liver damage caused by paracetamol toxicity - diets high in saturated fats and protein are protective.
It's been suggested, based on a rational understanding of processes which as I've said are nowhere being disputed, that paracetamol, by increasing glutathione consumption, will have adverse effects on the people most vulnerable to Covid.
To be honest I thought these effects were likely to be swallowed up in the noise of covid interactions, and appear as quite small risks in epidemiology until things were better understood.
I was wrong.
METHODS: We conducted a retrospective analysis of patients admitted at Washington Hospital Center between February 2020 and- June 2020. Patients older than 18 years of age, diagnosed with COVID-19 were included in the study. Those who were directly admitted to the ICU were excluded. Acetaminophen exposure was calculated using a formula for average adjusted daily acetaminophen: total acetaminophen divided by number of day’s medication was administered. Groups were stratified to non-exposed and exposed. Within the exposed groups, we further divided them into moderate (100-1000 mg/day) or high exposure(>1000 mg/day). Comparison between groups for continuous variables was conducted using Kruskal Wallis test. Association between two categorical variables was tested using Fisher's exact test.
RESULTS: The cohort included 524 patients with non-exposed (n=136), moderate exposure (n=256), and high exposure (n=132) categories. Multivariable logistic regression showed that patients who were exposed to acetaminophen had a significantly higher odds of being triaged to a higher level of care [3.01 (CI 1.4-7.07 p <0.007) in moderate exposure group and 3.44 (CI 1.49-8.54 p<0.005) in high exposure groups]. Secondary outcomes included longer length of stay (5 vs 10 days, p < 0.001), higher mortality (5.1% vs 16.5% p = 0.001) and higher risk of requiring the ventilator support (2.9% vs 15.5% p<0.001) in the exposed group.
CONCLUSIONS: Previous studies have demonstrated that up to 85% of patients with COVID-19 develop fever and acetaminophen is commonly used as a treatment. Our study showed that acetaminophen exposure was associated with worse outcomes. Further studies are required to investigate this association, in particular to see if having a greater number of febrile episodes is independently associated with these same outcomes.
Those are huge ORs. It's possible that fever itself, for which the paracetamol is being given, instead predicts the outcome.
In this paper, fever is associated with a 4x higher rate of adverse outcomes. This is concentrated in the symptomatic febrile cases, of whom only 4.8% received NSAIDs. Of course some studies say paracetamol is not an NSAID, others say it is, so it's possibly not even recorded correctly. However, as stated, this is a low correlation between fever and NSAID use, one which would not strongly support confounding-by-indication if it applied to the first paper..
So we have an unsatisfactory situation - a drug that WAS NEVER TESTED is being widely used by people with COVID-19. It's now associated with them getting worse. This could be due to confounding-by-indication, but no-one knows yet.
It's been three fucking years. I'm trying to follow the science, but it's always nodding off.
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1] Sestili P., Fimognari C. Paracetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness? (2020) Frontiers in Pharmacology, 11, art. no. 579944
3] Hwang J. Diets with corn oil and/or low protein increase acute acetaminophen hepatotoxicity compared to diets with beef tallow in a rat model. Nutr Res Pract. 2009;3(2):95-101. doi:10.4162/nrp.2009.3.2.95
4] Manjani L, Desai N, Kohli A, Arya R, Woods C, Desale S. Effects of acetaminophen on outcomes in patients hospitalized with COVID-10. Presented at: CHEST 2021; October 17-20, 2021; Orlando, FL/Virtual. Abstract A1072.
5] Chew, N W et al. “Fever as a predictor of adverse outcomes in COVID-19.” QJM : monthly journal of the Association of Physicians vol. 114,10 (2021): 706-714. doi:10.1093/qjmed/hcab023