Old drugs and an old supplement; new cheap weapons against the virus

By Jerome Burne

Lockdown and social isolation are drastic and magic money-tree expensive solutions to the Covid-19 crisis, but they are essential because the alternative would be even worse. If only we had a way of tacking the virus directly. Something that cut your risk of getting it and reduced the time in intensive care if you had a serious infection. 

Remarkably we do. Or, to be more precise, we have two cheap, old and unpatentable but very safe treatments, each of which has promising evidence that they could improve your protection and reduce your time in intensive care if that became necessary. But outside China, they are being ignored.

The catch is that one is vitamin C, which the medical profession has claimed for decades does little more than produce expensive urine, while the other is an ancient, pre-statin, very cheap heart drug that is rarely used called Dipyridamole (DIM). 

However, it looks as if vitamin C is coming in from the cold and the refusal of the pharmaceutical industry to investigate unprofitable drugs such as DIM will have to change. The Chinese medical establishment doesn’t share Western medical prejudice against vitamin C and both treatments are being seriously tested against Covid-19. Results so far are promising. 

New drugs won’t be coming soon

Meanwhile, pharmaceutical research in the West is focused on either new, very expensive anti-viral drugs of the sort that treat AIDS and come with a hefty dose of side-effects, or vaccines. Neither, despite optimistic claims they are just around the corner, are likely to be available soon, if they are properly tested. 

Old drugs like DIM, however, have already been used by doctors for years, so their side-effects and interactions are well known. Most drugs can do more than treat the disorder they were licensed for, but the information is buried in old medical reports. A program to discover others with anti-viral abilities would find ones like DIM that could be “repurposed” to treat infected patients. They would only need a short period of low-cost checking before being given to patients. 

Similar benefits are there for vitamins, supplements and nutrition which are rarely tested in large trials. Vitamin C is a plausible candidate because it has various virus-fighting abilities, such as making it harder for viruses first to infect cells and then to leave. 

Viruses are coated with two proteins, one of which they use to get into cells (hemagglutinin) and the other allows the billions of copies to cell has been forced to make to stream out (neuraminidase). Vitamin C reduces the effectiveness of both.

High dose vitamin C cuts hospital time

 It also increases the production of the immune-boosting compound interferon and speeds up the production of virus-fighting T-cells. Doctors in China are aware of its potential and are being encouraged to give 24 grams of intravenous vitamin C for patients with serious breathing problems 

One of these trials was reported on March 17 by Dr Mao from the Shanghai Public Health Centre who said that his group had treated over 50 moderate to severe cases of Covid-19 infection with high dose vitamin C via a drip (IVC.). Patients got either 10 or 20 grams a day for 7-10 days. All improved and there were no side-effects. The treatment also cut 3 to 5 days from the normal hospital stay of 30 days. 

In contrast to this proactive approach, earlier in the month, the BBC had issued the usual dismissal of the vitamin in an article about fake claims for CoVid-19 in Italy. This stated firmly: ‘And to be clear, there is no evidence …that large doses of vitamin C will stop the virus.’ 

In fact, a randomised trial of the benefits of vitamin C on Covid19 patients with acute respiratory problems was already underway in at Zhongnan Hospital in Wuhan University. It had started in February, involved 140 patients and is expected to finish by the end of September. It’s registered at the main clinical trials database held at the US Library of medicine.

Two antivirals no better than usual treatment 

It’s true that there are no large-scale trials of vitamin C but what organisation should do them? Drug companies certainly have no interest. All the same, studies are done but positive conclusions are simply ignored, such as the review of RCTs that found that high dose vitamin C helped against pneumonia. A finding likely to be useful in a pandemic involving breathing. So would knowing vitamin C could help intensive care (ICU) patients with an infection or who were being ventilated.

The need for something other than more new drugs became very clear a few days after Dr Mao’s talk. On March 20th the New England Journal of Medicine carried the report of an RCT of 199 hospital patients with serious Covid-19 infection treated with a combination of two heavyweight AIDS drugs – Lopinavir and Ritonvir. It found no difference between the group getting the drugs and those getting normal care. The major side effects of this drug combo are pancreas failure, liver toxicity, diabetes and redistribution of body fat. The journal article ended by saying that ‘future trials …may help to confirm or exclude the possibility of a treatment benefit.’  

Should we really be funding further trials on drugs that have been shown not to work, which will expose elderly patients, quite likely with other disorders, to the risk of serious side-effects? Isn’t it a failure of care to continue ignoring vitamin C – virtually side-effect-free – in favour of continuing to research drugs that are ineffective and likely to be damaging?

For information on vitamin C research into its ability to cut the risk of developing viral infections taking hold, check out the website run by nutritionist and long-time vitamin C advocate, Patrick Holford. A recent article of his on Facebook mentioning the RCT of vitamin C now underway in China was stamped with a “Fake news” notice without warning or further details. 

An old drug that’s a remarkable viral fighter

The other candidate for an ‘oven-ready’ antiviral is the repurposed drug dipyridamole, which also produces a strong interferon response and reduces the rate Covid-19 is able to churn out clones of itself from the cells it has hijacked. It was recently put through a small trial to find out how it worked and how effective it is. The team was led by Xiaoyan Liu of the Department of Hematology, at Zhongnan Hospital of Wuhan University. You can see the report atmedRxiv, an archive of completed but unpublished clinical trials.

The paper tells how it was discovered in an FDA (Food and Drug Administration) library of approved drugs when the team were following the repurposing approach and searching for something to tackle the increased tendency of the blood of infected patients to clot, along with a drop in the body’s ability to fight off an infection. 

The fact that it was old, so its patent had run out – making it very cheap – was no bar to investigating it, as it would be in Europe and the US where bottom-line-driven pharmaceutical companies dominate drug development. The drug looked promising because research suggested it would be able to boost the body’s defences and reduce some of the virus’s malign effects.

 A broad spectrum of anti-viral activity

One of the abilities is to lower the raised risk of blood clotting that Covid-19 and other viral infections can cause. This is what the drug was used for originally. It can also tackle a dangerous combination found in the bloodstream of an infected person – too few white blood cells (lymphocytes) that fight infections and too many protein fragments (D-dimers – produced in response to shock). Dipyridamole can boost lymphocytes and clear out D-Dimers. 

There have now been 102 clinical trials carried out in China which show that dipyridamole has a ‘broad spectrum of antiviral activity’. These include suppressing inflammation and preventing acute injury to the lungs, heart, liver and kidney.  

The team ran a small pilot study of 10 patients – 6 with mild infection and 4 with a serious one – which found that half the seriously ill ones and all those with a mild bout could be discharged from hospital after two weeks. DIP cut the rate the virus was copying itself (replication) in half. Those getting the drug in both groups went into remission and were discharged faster.

Dr Liu at the Wuhan University Hospital writes;’ Covid-19 infected patients could potentially benefit from DIP therapy as an add-on by reducing viral replication, suppressing hypercoagulability and enhancing immune recovery. Larger scale clinical trials of DIP are needed to validate these therapeutic effects.’

The virus fighter that also helped to beat cancer

One of the few non-medical people in the UK with a detailed knowledge of the effects of dipyridamole is Jane Mclelland, a former Chartered Physiotherapist. She found it 20 years ago when she was doing her own search for old, off-patent drugs that might help treat her Stage 4 lung cancer. A very radical and eccentric approach to cancer then and still largely ignored by the establishment today.

At the time her life expectancy was a matter of months. She’s now the author of a best-selling book – How to Starve Cancer and runs a Facebook page which provides information about cheap old drugs that may help.

 Dipyridamole has a history as a viral treatment, being used alongside the early AIDS drugs to treat HIV. She is now campaigning to persuade drug regulators to make it available on the NHS as a low-cost treatment for patients suffering from the advanced effects of Covid-19. Her petition can be found here

We are all being asked to make sacrifices to combat the spread of the virus but the current measures might not have to be so drastic if we didn’t put all our faith competing drug companies to come up with effective new treatments sometime soon, hopefully. 

All this and very few side-effects

The pandemic has already shown that that privatised commercial medicine can’t protect us on its own, so if we need the state to lock down cities and inject billions into the economy, why not set up an NHS unit to dust off more promising old drugs and put them to work fast, saving millions of pounds. In other areas, the failure of the commercial approach to producing badly needed public health treatments, such as new antibiotics, has led to calls for a not-for-profit approach to drug development. 

Repurposed drugs can be selected for a low risk of side effect. Those listed for dipyridamole are abdominal or stomach cramps; diarrhoea; dizziness; headache; flushing; nausea.

 Compare those with the side-effects that come with the antiviral ribavirin, being used against Covid-19:  depression; thinking about hurting or killing yourself; excessive worry; starting to use street drugs or alcohol again if you used these substances in the past; difficulty concentrating; difficulty falling asleep or staying asleep; memory loss.

The new unit could break new ground and seriously investigate and test the ability of supplements, nutrition and lifestyle change to improve resistance. The success of a low carb diet as a treatment for diabetes shows what this approach can achieve.

Jerome Burne

Jerome Burne

Jerome Burne is the editor of HealthInsightUK. He is an award-winning journalist who has been specialising in medicine and health for the last 10 years and now works mainly for the Daily Mail. His most recent book “The Hybrid Diet” was written with nutritionist Patrick Holford, published 2018. Award: 2015: Finalist for 'Blogger of the Year' Medical Journalists' Association.

7 Comments

  • Don’t be silly! Expect anyone in an NHS setting to even go anywhere near IV vitamin C to save someone’s life? The treating doctor would be afraid of getting struck off after telling you it’s nonsense!

    And it’s not just against diabetes that a low carb (ketogenic) diet can show success but against viral infections as well:

    Investigators from The Department of Comparative Medicine, from Yale School of Medicine report the effect of the ketogenic diet on the T cell immune function in mice exposed to influenza virus. The investigators examined transgenic immunocompetent mice exposed to an intranasal challenge of influenza virus. The mice were fed ketogenic diet prior to the infection. The team studied survival and weight loss on the mice. This study noted that mice that were fed ketogenic diet had better survival and decreased loss when compared to mice that were not exposed to the ketogenic diet. The investigators sought to analyze the molecular underpinnings of this finding. They performed transcriptome analysis of the mice’s lungs noting that several genes were upregulated in ketogenic diet fed mice; particularly genes associated to δ T cell responses were increased; including number of cells in lung tissue, and release of cytokines related to this specific cell type. The mice consistently showed lower virus titers than controls. The investigators then tested whether the ketogenic diet was actually exerting an effect on these T cell populations by comparing the function in mice fed a non-ketogenic high caloric density diet. They noted that these effects were specific for the ketogenic diet fed animals only. Additionally, the investigators noted that the ketogenic diet increased δ T cell proliferation, noting that this was not directly related to increases in β hydroxybutyrate, the primary energy substrate during glucose deprivation associated to ketogenic diet, but rather finding that the effect on δ T-cell population is mediated by favoring fatty acid oxidation. This paper concludes that the effect of ketogenic diet exerts a potentially previously unrecognized immune effect.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051856/

    It’s worth noting that the mice were protected from a lethal influenza infection.

    • Editorial

      That is fascinating, Many thanks. I had seen suggestion that viruses seemed to be more active/infectious at higher blood glucose levels and a suggestion that therefor a low carb diet could be a useful prophylactic approach. But when i tried – briefly – to get support for this idea on the web, all i could find were reports that viral infection raised glucose levels, raising question about which was cause/effect? So I didn’t mention it.

      But fact suggestion that it is Ketone production, rather than reducing glucose levels per se, that is having an effect fits better with other research in cancer which has found ketones can make beneficial genetic changes – woman an Imperial doing this research – can provide link if useful. Got the point at the end about the increased T-cells not being linked to one of markers for ketone levels -hydroxybuterate – but can you explain more about that is happening with fatty oxidation role -how/why?

      • The study was followed up in “The Scientist”. OK, the article has the usual caveat of extrapolating mice studies to humans but it’s certainly interesting reading. And thinking about a survival advantage, when were humans historically most likely to be in a state of ketosis? In the middle of winter, just when influenzas were prevalent and people susceptible. That’s of course before the days of sugar laden fake food. Food for thought…?

        Anyway, the article from “The Scientist” below gives some interesting background. And note the normally lethal dose of H1N1 administered, and as it should have been done – intranasally.

        The low-carb, high-fat diet increases the presence of gamma-delta T cells in the animals’ lungs, improving a mucus barrier against the virus.

        Mice fed a ketogenic diet—in which 90 percent of calories come from fat and less than 1 percent from carbohydrates—were less susceptible to the influenza A virus, according to a study published today (November 15) in Science Immunology. The protective effects seem to be mediated by an increase of so-called gamma-delta T cells in the animals’ lungs that induce the epithelial cells in the airway to make more mucus to trap the virus.

        The project began as a discussion between Ryan Molony, at the time a grad student in the Yale School of Medicine lab of Akiko Iwasaki, and Emily Goldberg, a postdoc in Vishwa Dixit’s lab at Yale. Dixit’s group had shown in 2015 in mice and in human cells that a ketogenic diet blocks an inflammation pathway triggered by a protein complex that plays a role in some autoimmune disorders. A year later, Iwasaki’s group published work showing that this protein complex also drives lethal influenza infection. The two groups formed a collaboration to connect the dots and investigate whether or not a ketogenic diet could stop mice from dying of the flu virus.

        They started by keeping mice on a normal diet, in which 18 percent of calories come from fat and 58 percent from carbs, or feeding them a ketogenic diet for seven days, and then infecting them intranasally with H1N1 influenza. All animals eating the normal diet were dead by the fourth day after infection, while half of the mice fed the keto diet survived. The keto diet–fed mice also lost less body weight, maintained higher blood-oxygen saturation levels, and had lower levels of the virus in their blood than their counterparts that ate normal chow.

        Humans and mice have two types of T cells: alpha-beta T cells, which are well studied and specific to pathogens, and gamma-delta T cells, which detect signs of stress, are more numerous in the lungs, skin, and gut, and are much less well understood. The researchers found that mice fed a ketogenic diet have about four times the number of gamma-delta T cells in the lungs as mice fed a normal diet by the third day after infection. Then they analyzed gene expression in flu-infected lungs from mice fed the keto diet and determined that the gamma-delta T cells were protecting the mice in a surprising way.

        “Typically, T cells are thought to control viral infection by killing the infected cells. What we found was that instead of killing, gamma-delta T cells modify the environment . . . to protect the host against the virus,” writes Iwasaki in an email to The Scientist. “These T cells modify the airway epithelial cells to produce more mucus that can trap the virus in its tracks.”

        These two ideas—that a diet that the mice are being fed contributes to protection by improving barrier function and that the mechanism of that protection is being mediated by gamma-delta T cells—haven’t received much attention in influenza biology, says Paul Thomas, an immunologist at St. Jude Children’s Research Hospital who did not participate in the study. “Why are gamma-delta T cells an effector of a diet-induced changed in metabolism” is one open question, he adds, and another is “whether or not the same pathways exist in humans, and if they do, how that might affect how we handle influenza infection.”

        The findings indicate that the keto diet could have similar protective effects in people.

        “Obese and diabetic patients incur more hospitalizations and have increased severity of influenza infections each year,” Julie Jameson, an immunologist at California State University, San Marcos, who did not participate in the work, writes in an email to The Scientist. It’s already known that a ketogenic diet can help these patients lose weight and improve their cholesterol levels and blood pressure, she adds, and this study raises the possibility that it “may have even more health benefits than previously reported.”

        According to Jameson, it is still not clear what the consequences of a long-term ketogenic diet are. “This study examines a one-week, acute time point. It is important to know whether gamma-delta T cells would continue to accumulate in the lung and whether this would be beneficial,” she explains.

        And it’s probably best to hold off on switching over to a ketogenic diet during flu season for now. “We do not extrapolate the findings in mice to people,” cautions Iwasaki, “but this study provides a rationale for looking into whether people on [a] keto diet have more gamma-delta T cells and whether they are better protected from flu disease.”

        E.L. Goldberg et al, “Ketogenic diet activates protective γδ T cell responses against influenza virus infection,” Science Immunology, doi:10:1126/sciimmunol.aav2026, 2019.

        https://www.the-scientist.com/news-opinion/keto-diet-protects-mice-from-flu-66731

  • Maybe vitamin C doesn’t work for Corona virus – 19 (a.k.a. The Beer bug) but it did on a near-fatal dose of Swine Flu, as Allan Smith of NZ found out some years ago.
    Featured on a You Tube video, a ’60 Minutes’ episode. Very embarrasing for the hidebound medical professionals, more so as his leukemia …. vanished.
    Interesting to note, when conscious his Wife supplied him with (oral) Liposomal C which has a cellular take-up rate similar to intra-venous, at a fraction of $$$.

  • From my perspective as a journalist, this is exciting, backed up with your usual research and referencing rigour, Jerome. Thank you and not just for putting spotlight back onto Vitamin C as possibly helpful adjunctive treatment for COVID-19. The heads-up on dipyridamole is just as exciting. But what a commentary on the cynicism of the drug industry and its medical profession proxies. Sad that dipyridamole is one of many drugs that physicians now dismiss out of hand because it is cheap! That’s despite its low-risk profile and high level of robust data on how it works.

  • Very interesting information. I hope that by shearing this information widely the patients by requiring these treatment put more pressure on the system. Hopefully changes will come.
    Thanks for your research

  • Simple questions,

    “Who Profits ?” – Not necessarly right now, but/years/decades to come.

    I can’t help feeling this whole Pandemic is a Training Exercise, in teaching Obedience to the masses, whatever the co$t. Remember SARS? Swine Flu? Zika ? Measles outbreaks?

    And why is Germany doing SO well ?
    Will be interesting to see how Sweden eventually fares, – lock up the vulnerable only, and Belarus, – virtually nothing.

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