COVID-19 mostly kills old people, while little children usually take coronavirus in a stride without so much as a sneeze. Why? Obviously because children drink milk. And what is found in milk? Lactoferrin. Pandemic, solved.
Lactoferrin (also known as lactotransferrin) is a iron-transporting protein secreted into milk (where it was originally found, hence the name) as well as into all other bodily secretions, including tears, saliva and snot, where it exerts some antimicrobial function. Basically, the very same mucous membranes via which the coronavirus enters the body are chock-full of lactoferrin and yet it still doesn’t help. Nevertheless, some scientists used their superior über-human intelligence to reason that in order to survive COVID-19, you need to apply lactoferrin via conveniently subscription-free commercial supplements. Because lactoferrin is a supplement in desperate need of a new market, having utterly failed to do much about diabetes or apparently any other disease it was tried against. So now lactoferrin is there to cure COVID-19.
While the rest of the world obsesses with hydroxychloroquine and Vitamin D, Italy fell under the spell of lactoferrine, or lattoferrina in Italian. The magic cure is being heavily pushed by Elena Campione, professor for dermatology and venereology at the University Tor Vergata in Rome, and her colleagues there. Imagine Dr Campione as the Italian answer to Didier Raoult, they both have long hair and a magic cure against COVID-19. Campione is also on all national media where she explains:
“One fact about all was evident in the pandemic: children did not get sick or had mild symptoms. Lactoferrin is a protein with antiviral properties, we decided to treat Covid-positive patients at the onset of the disease and asymptomatic patients. Incredibly, after ten days from the therapy, we observed the disappearance of the symptoms and then we obtained the negativization of the swabs“.
How did we get there?
In May 2020, a “Hypothesis and Theory” article was published in Frontiers (are you surprised?), where almost 200 references were supplied to prove that yes, lactoferrin must be the cure for COVID-19.
Douglas B. Kell, Eugene L. Heyden and Etheresia Pretorius The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria Frontiers in Immunology (2020) DOI: 10.3389/fimmu.2020.01221
The brain behind the study is Etheresia Pretorius of Stellenbosch University in South Africa, and she concludes:
“LF may therefore be an excellent supplement to take, not only as a contribution to prevention but perhaps as a therapy in the event COVID-19 is diagnosed.“
Pretorius previously was served two retractions by the journal Blood for bypassing peer review by sneaking in novel clinical studies disguised as teaching papers. Now she went for Frontiers.
The opinion piece was immediately covered as a scientific breakthrough by a German pharmacy newsletter which also informs the readers which product to buy:
“SanFerin® can be used in the prophylaxis and possibly also in the therapy of bacterial and viral diseases of the respiratory tract, this should also apply to the currently rampant COVID-19 epidemic, especially with regard to the prophylaxis before COVID-19.”
Good to know you can always trust your local pharmacist. If they should run out of lactoferrin, you can always buy homeopathy. But the pharmacy newsletter covered also another study from University of Michigan, USA, also from May 2020, which is a preprint:
Carmen Mirabelli, Jesse W. Wotring, Charles J. Zhang, Sean M. McCarty, Reid Fursmidt, Namrata S. Kadambi, Anya T. Amin, Teresa R. O’Meara, Carla D. Pretto, Tristan Frum, Jason R. Spence, Konstantinos D. Alysandratos, Jessie Huang, Darrell N. Kotton, Christiane E. Wobus, Kevin J. Weatherwax, George A. Mashour, eSamuel K. Handelman, Matthew J. O’Meara, Jonathan Z. Sexton Morphological Cell Profiling of SARS-CoV-2 Infection Identifies Drug Repurposing Candidates for COVID-19 bioRXiv doi: 10.1101/2020.05.27.117184
This preprint is constantly being evoked as confirmation that Campione’s lactoferrine results are scientifically solid and independently verified. The Michigan study has been updated twice since, most recently in late September 2020. It has not appeared in a peer reviewed journal yet, but still announces:
“In particular, we discovered that lactoferrin is an effective inhibitor of SARS-CoV-2 infection with an IC50 of 308 nM and that it potentiates the efficacy of both remdesivir and hydroxychloroquine.“
Well, what do you say, lactoferrin potentiates both HCQ and remdesivir (which was also recently proven not to work, but only after the EU Commission signed over an obscene amount of money to Gilead). I am convinced now, off to the pharmacy for some lactoferrin! Speaking of, the last author Jonny Sexton is the owner of pharma start-up companies like Curl Bio which sells diabetes medicine, and remember this is what lactoferrin is still being used for, even if clinically unsuccessfully.
Now that we talk about preprints which don’t make through peer review, here is the main character of this story: the dermatologist Elena Campione of Tor Vergata University.
Dr Campione’s preprint appeared in August 2020:
Elena Campione, Caterina Lanna, Terenzio Cosio, Luigi Rosa, Maria Pia Conte, Federico Iacovelli, Alice Romeo, Mattia Falconi, Claudia Del Vecchio, Elisa Franchin, Maria Stella Lia, Marilena Minieri, Carlo Chiaramonte, Marco Ciotti, Marzia Nuccetelli, Alessandro Terrinoni, Ilaria Iannuzzi, Luca Coppeda, Andrea Magrini, Nicola Moricca, Stefano Sabatini, Felice Rosapepe, Pier Luigi Bartoletti, Sergio Bernardini, Massimo Andreoni, Piera Valenti, Luca Bianchi Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: randomized clinical trial, in vitro and in silico preliminary evidences bioRxiv doi: 10.1101/2020.08.11.244996
A significant coauthor is the microbiology professor and lactoferrin-expert Piera Valenti of the Sapienza University, also in Rome. Valenti is likely the brain behind the lactoferrin idea for COVID-19, since:
“In 2013, she received the Order of Merit of the Italian Republic, Grade Commander, for scientific achievements in the study of the functions of lactoferrin.“
The preprint declared:
“We performed a randomized, prospective, interventional study assessing the role of oral and intra-nasal lactoferrin to treat mild-to-moderate and asymptomatic COVID-19 patients to prevent disease evolution. Lactoferrin induced an early viral clearance and a fast clinical symptoms recovery in addition to a statistically significant reduction of D-Dimer, Interleukin-6 and ferritin blood levels.“
A “randomized” “Clinical trial”, as authors call it in the paper, with the listed principal investigator Campione, seemingly without any knowledge how to do a proper clinical trial, even a small-scale one, and without even knowing what “randomized” actually means (where patients are randomly assigned to treatment vs placebo arms). Please allow me to quote for your humorous entertainment:
“Eligible patients were over 20 years old, with a confirmed COVID-19 rRT-PCR at the naso-oropharingeal swab and blood oxygen saturation (SPO2) > 93% or Horowitz index (PaO2 / FiO2) > 300mmHg. Patients did not receive any other treatment against SARS-CoV-2. […] ICU COVID in-patients were excluded.
A control group of healthy volunteers, with negative rRT-PCR at the naso-oropharingeal swab, was included in the study in order to be paired to the above case-group. The “matched-pair-analysis” concerned the structural and clinical characteristics of the corresponding group. Placebo or liposome arms have not been included due to ethical reasons.“
Did you get it, reader? There was no control group in reality. Even the lunatic Didier Raoult compared his chloroquine-treated COVID-19 patients with other COVID-19 patients (at least initially, and with lots of dishonest trickery and cherry-picking). Here treated twenty-two COVID-19 patients (all of whom with mild symptoms only, and as soon someone got worse they got excluded) are compared with… ten untreated and uninfected people. They did use Raoult’s insane argument that using standard care alone as placebo is unethical if you are convinced in advance that your drug works. But why do they call it “randomized”, is it because they picked random students off the corridor as healthy volunteers or what? Anyway, how clinical professors can be that…, let me put it kindly, that ignorant, is beyond me. Not just them:
“The trial was approved by the Tor Vergata University Hospital Ethics Committee (Code 42/20). It was registered at www.clinicalTrials.gov (NCT04475120)“
That trial was originally supposed to have 60 patients. It was also supposed to have two treatment arms with two different lactoferrin doses (“oral and intra-nasal formulation“) AND two control arms with actual COVID-19 patients undergoing standard care. At the end, there was just one group, and no control. No wonder no journal seems to be interested in publishing it.
Sylvie Coyaud has a valid point here:
“…the panacea would have
– induced an early elimination of the virus 15 days after treatment in 31% of patients and 30 days in the others.
If anything, it would show that liposomal lactoferrin prolongs the duration of infection in 69% of patients. Except for severe covid, viral load elimination occurs on average within 14-16 days of onset of symptoms.”
It gets funnier. The pretence of a “clinical trial” ended on 2 July, according to records. On 11 July, these very same clinical trial experts published an opinion paper in an MDPI journal where they “propose designing a clinical trial to evaluate and verify its effect using a dual combination treatment with local, solubilized intranasal spray formulation and oral administration.” Is this a sign of high learning and intelligence? I don’t know, you tell me.
Elena Campione, Terenzio Cosio, Luigi Rosa, Caterina Lanna, Stefano Di Girolamo, Roberta Gaziano, Piera Valenti and Luca Bianchi Lactoferrin as Protective Natural Barrier of Respiratory and Intestinal Mucosa against Coronavirus Infection and Inflammation (2020) doi: 10.3390/ijms21144903
Now, MDPI can be described as a discount version of Frontiers (both Open Access publishers are based in Switzerland) and sometimes even as the last stop on the “legal” side of scholarly publishing before you go for OMICS. And yet Italian media jumped on it as it was an official WHO announcement.
The authors explicitly declared no Conflict of Interests whatsoever in both papers. Yet also in both papers, they wrote “We thank Technology Dedicated To Care (TDC)“, which is an Italian lactoferrin seller owned by the Biancardi family. Below is one of the Biancardis thanking the Tor Vergata scholars, while reminding that their research proved that lactoferrin cures COVID-19. Surely there will be more to Biancardi’s gratitude that just a tweet.
So now Italy is in the thrall of Elena “Lattorerrina” Campione. The utterly data-free MDPI opinion paper was covered in La Repubblica on 29 October as a breakthrough of clinical research. Before screaming at “stupid journalists”, dear reader, be aware that it was the University Tor Vergata itself who claimed that the MDPI opinion paper was actually clinical study by their professors Campione and Luca Bianchi, further verified in the lab by Professor Valenti’s team. The press release from 2 September was titled:
“Lactoferrin, a probable response to Covid”
and concluded: “The effect of lactoferrin against Covid can also be considered in prevention as an effective weapon in controlling the infection.“
On top of that, already in July 2020 the Italian National Order of Biologists (can it get even more authoritative?) issued the exactly same press release from Tor Vergata University celebrating the MDPI study. The Order even posted a video interview with Campione on the national Rai TV. Update 18.11: I learned that the president of the Order of Biologists is the politician Vincenzo d’Anna, who is also deep into anti-vaxx and peddling whole grain cures against mercury poisoning.
This is how, an unpublishable preprint somehow mutated and was merged post-mortem with a dishonest opinion paper in a shady MDPI journal, to emerge as a national salvation strategy.
Campione, unable to get her various versions of the story straight, was quoted in La Repubblica:
“We started with a sample of about 100 positives with mild or asymptomatic symptoms who were cured only with lactoferrin. It was the same team of researchers who went house to house to administer the protein.”
Wait what? What is she talking about suddenly, if the bioRxiv preprint only mentions 22 mild or asymptomatic COVID-19 patients? Massimo Andreoni, virology professor and director of an infectious disease centre at Tor Vergata, confirmed the number of 100 patients and went to extol Campione’s clinical results in Italian media and in the above press release.
Update: Thanks to Sylvie Coyaud, I now quote from a letter in which Camipone et al reply to peer criticism of their bioRxiv preprint:
“The truth is that no clinician or researcher from academic institutions has contested the design of the study currently underway in accordance with the procedure adopted for research, which concerns the use of a dietary supplement, regularly reported to the Ministry of Health, and which involved an initial number of 32 patients to include today more than 100.“
So we learn that scientific peer are not allowed to criticise this study, while its principal investigator dermatologist and her colleagues proceed with their bizarre “randomized” clinical trial and have treated already over 100 COVID-19 patients. Is this actually legal, a question to the allegedly informed Italian authorities? In any way, Campione’s French role model Raoult treated thousands in this way with chloroquine, there is a lot to catch up!
Envious about so much success of their Rome colleagues with a protein from milk, spit and snot, the University of Bologna issued their own press release, about a different food supplement to cure COVID-19.
It’s spermidine. Don’t ask.
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http://dbkgroup.org/why-i-am-boycotting-the-journal-blood/
covers the bits you seem to have missed in your gratuitous dissing of my collaborator Prof Pretorius, including the fact that the so-called retractions were actually no such thing and that the material was in fact published in Cell. Maybe you want to criticise their Editors too? I am all for exposing bad science, but this is just a lousy, lousy job, and way wide of the mark. Hardly leads one to assume that any of the others are better researched. You should be ashamed, but won’t be.
My ORCID at https://orcid.org/0000-0001-5838-7963 and an H-score of 114 https://scholar.google.com/citations?user=DOrAFFEAAAAJ&hl=en if you want to check out my academic CV.
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You came to the wrong place to boost with Cell and your phony h-index. And anyway, which Cell paper, you forgot to link to it in your whinny blogpost?
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Instead of apologising for doing lousy ‘journalism’ by not checking all sides of what you consider a ‘story’ you make it clear that you have no real interest in the facts at all, and just want a bit of attention. But that does not surprise me at all.
Maybe you don’t know what the word ‘phony’ means (look it up) but there is nothing ‘phony’ about my H-index; it can be checked by the elementary procedure of going to that website noted above. I’m just sticking to the facts. Lactoferrin may or may not help vs Sars-Cov-2 as the experiments have not yet been done; however, we adduced evidence that it was very much worth a look, and would for sure not do any harm. Since the paper is Open Access (and FWIW was peer-reviewed), anyone who cares to can read it and make up their own minds (and do an RCT).
And since no doubt you’d like to know, I have no personal interest in this, financial or otherwise. I am just serving, in an attempt to help folk avoid the worst manifestations of this ghastly virus, as a proper scientist. I do this by using my ability to access the literature, think about it, and summarise it accurately, I suggest you do the same in future. And maybe publish it in a peer-reviewed journal, too.
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Thanks for patronising, Douglas. Of course your h-index is real, I should clarify that “phony” is the way you achieved it, by publishing oodles of crap in what you call “peer reviewed journals”. Happy now?
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Very, since you make it abundantly clear to your readers that you prefer opinionated Trump-level ramblings (that are presumably intended to impress someone) to the established procedures of science that are designed to produce facts. I shan’t bother to explain for your readers, who can look it up https://en.wikipedia.org/wiki/H-index, that H-indices are based on being cited by people, who mainly think the work is worthwhile. The simple production of ‘oodles of crap’ (including in blog form) does not of itself produce citations in peer-reviewed journals. That is why real scientists value that metric, why peer review is considered to have merit, and why high values of an H-index are not ‘phony’ even by your distorted metric. Over and out.
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So you produce oodles of self-citing papers in crap journals, all to impress people with your phony h-index? I wrote about folks like you, we all had a laugh.
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Wow. The author of this article is a sarcastic A_ _ hole. A cynical know it all who does no real review of lactoferrin and the many thing it truly helps, prevents, and cures. We who read and study have no desire to be a fool like you and believe the crap you print.
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Now we can all choke on our jokes about lactoferrin, because science has spoken. The Italian miracle cure for COVId-19, sold as supplements, was vindicated in a PNAS study:
Carmen Mirabelli, Jesse W. Wotring, Charles J. Zhang, Sean M. McCarty, Reid Fursmidt, Carla D. Pretto, Yuanyuan Qiao, Yuping Zhang, Tristan Frum, Namrata S. Kadambi, Anya T. Amin, Teresa R. O’Meara, Jason R. Spence, Jessie Huang, Konstantinos D. Alysandratos, Darrell N. Kotton, Samuel K. Handelman, Christiane E. Wobus, Kevin J. Weatherwax, George A. Mashour, Matthew J. O’Meara, Arul M. Chinnaiyan and Jonathan Z. Sexton Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19 PNAS (2021) DOI: 10.1073/pnas.2105815118
The paper concludes that the relatively cheap supplement lactoferrin works just as well as the very expensive COVID-19 drug remdesivir (which was more recently to found to barely or not work at all, but never mind):
Lactoferrin is highly expressed not just in milk, but also in tears (2 mg/ml or 0.6 mM), saliva (8 µg/ml or 2.6 µM) or snot (1 µg/ml or 300nM, data for humans). Basically, the IC50 of 50 nM for lactoferrin against the coronavirus in vitro that Michigan study determined may sound like a breakthrough game-changer news in the fight against pandemic, but…
It’s already many-thousands more concentrated in the fluids of mouth, nose and eyes already, and apparently still does little to prevent the SARS-CoV2 infection! And if you aim to increase lactoferrin further than that by taking commercial supplements of the iron-binding protein, COVID-19 will be the by far the smallest of your problems. You may wonder how this masterpiece passed peer review at an elite journal? It didn’t. The paper was accepted via the notorious “contributed” track for National Academy of Sciences members:
“Contributed by Arul M. Chinnaiyan, July 9, 2021 (sent for review March 25, 2021; reviewed by Matthew L. Albert and Sumit Chanda)“.
Never mind.
The University of Michigan press release quotes the lead author Jonathan Sexton:
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Lactoferrin is a metal ion transport protein (e.g. iron and zinc). There is a fair amount in human plasma, so no sense injecting more. If you take it orally, it will be broken down in the gut. Who cares what it does in cell models, since it’s neither necessary or useful as a drug. Won’t someone please think of the physiology?
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Odd how it works then…. lots of things get through the gut that aren’t supposed to. They do so via Peyer’s patches. You can look it up. It’s physiology.
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Dear Douglas Kell, CEO BBRSC 2008-2013,
Why don’t you take a look at the problematic publications ay a well-know BBSRC
institute?
https://forbetterscience.com/2021/01/04/david-argyle-can-bullying-lead-to-bad-science/
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How much Lactoferrin does one have to eat to achieve a concentration significantly higher than the ~300nM already present there? Especially given that the alleged IC50 of SARS-CoV2 inhibition is merely 50nM?
https://www.researchgate.net/figure/Reported-human-blood-lactoferrin-levels_tbl1_15525879
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No, I’m saying it does not and cannot work. Unless a lactoferrin-deficient patient chugs grams of it. It’s biology. Peyer’s patches are lymphoid tissue, by the way.
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a national salvation strategy
HA HA Leonid misspelled “salivation”.
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Who is laughing now, Mr Smut?
Akbar Shoukat Ali , Syed Shahzad Hasan , Chia Siang Kow , Hamid A. Merchant
Lactoferrin reduces the risk of respiratory tract infections: A meta-analysis of randomized controlled trials
Clinical Nutrition ESPEN (2021) doi: 10.1016/j.clnesp.2021.08.019
“A total of nine RCTs were eligible for this review, of which six were included in the meta-analysis. Overall, two studies demonstrated a high risk of bias. The meta-analysis revealed a significantly reduced odds of developing respiratory infections with the use of Lf relative to the control (pooled odds ratio = 0.57; 95% confidence interval 0.44 to 0.74, n = 1,194), with sufficient evidence against the hypothesis of ‘no significant difference’ at the current sample size.
Conclusions
The administration of Lf shows promising efficacy in reducing the risk of RTIs. Current evidence also favours Lf fortification of infant formula. Lf may also have a beneficial role in managing symptoms and recovery of patients suffering from RTIs and may have potential for use as an adjunct in COVID-19, however this warrants further evidence from a large well-designed RCT.”
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