Nose / throat treatments for respiratory infections

After hearing various people interested in nasal sprays for preventing covid or the common cold, I did a shallow dive on what might be worth trying in this area.

Overall, there are several treatments that seem safe and cheap and some of them are probably effective. A few (carrageenan and HPMC) seem to prevent infection, and the others reduce the severity of an infection once you have it. Some may also reduce your risk of infecting others if you’re already sick.

Obvious disclaimer: None of this replaces a vaccine or medical care. But it would be awesome if there were fewer colds in my house, if we could all get over them faster, and if we had gotten over covid sooner.

I looked at ingredients you can currently buy (in some country), not stuff that’s not on the market. In some cases you can get them e.g. on Ebay from other countries where they’re available without prescription. I only looked at things with human trials, not things with only in vitro or animal trials.

My understanding is that treatments aimed at the nose and throat can make sense because that’s where upper respiratory infections often first take hold. E.g. covid reproduces in nasal cilia cells for the first 24 hours after exposure before spreading to the rest of the body. A lot of antiviral treatments are known to kill covid in a petri dish, so they might also kill it in your nose and throat.

A lot of the research here is small preliminary studies on covid, often without randomization or control groups. I’m frustrated that in 3 years there haven’t been larger, better studies published – though there are some in the works. I suspect part of this is that the ingredients are cheap and unpatentable, so no one is going to make a lot of money off them. Some of the studies are funded by the companies making the product.

If you’re excited to dig into this more, I would love for you to make this review better!

I would also be excited to see more research on some of these cheap treatments, if anyone reading has the power to make that happen.

Povidone iodine

Povidone iodine has long been used as an antiseptic, and is considered safe to use in the nose and throat.

Study in Bangladesh: 606 people with covid were randomized to use a 1% iodine mouthwash, nose drops, and eye drops vs. water. The ones using iodine were much less likely to test positive at day 7 (3% vs 70%), and were less likely to need oxygen (3% vs 21%) or to die (1% vs 6%). If this is representative of what would happen at a larger scale, it seems like a huge deal and I’m confused why there hasn’t been more study of this. There are a bunch of studies that never finished or never published results – maybe that’s because they didn’t find iodine effective and the researchers didn’t put the time into publishing the null result?

Another study in Bangladesh (189 people): indicates that iodine spray or nasal wash can make you test negative at least temporarily. They took symptomatic people with covid, gave them a nasal spray or nasal wash to use one time, and then collected a second PCR test right away. Some people do test negative after applying the iodine, but this doesn’t seem that relevant to whether you get better sooner. .5% nasal irrigation worked best. 

This does make me think it might be good to use something like this if you know you have covid and need to be in a public place e.g. to get medical care. Or before a situation where you’re exposing people a lot, like a dentist visit.

A small (24 person) study found no significant difference in viral load after using povidone iodine mouthwash, gargle, nasal spray, and nasal ointment 4 times a day for 5 days. 

Iodine might mess with your thyroid if you use it a lot. From that last study: “Thyroid stimulating hormone elevation (median [IQR], 3.4 [2.6-4.3] mIU/L vs 2.1 [1.4-3.1] mIU/L at baseline) was observed in all patients after 5 days of PI exposure, exceeding the upper normal value in 5 patients, with a return to baseline values 7 to 12 days later.”

Products:
Betadine, Viraldine, Immunemist, various others.

Nitric oxide 

Nitric oxide is not the same as nitrous oxide. It’s used in a lot of our body’s processes, and we produce it in response to food including leafy greens. I’m confused about how it’s actually administered — it seems like various things cause your body to make nitric oxide, so the things described as nitric oxide sprays don’t actually contain nitric oxide as an ingredient, but contain stuff that results in more nitric oxide in your body?

A UK study (80 people) found that covid patients using nitric oxide nasal spray (NONS) felt better sooner: “NONS subjects typically reported being better by day 2-4 on treatment, whereas the placebo subjects typically did not report feeling better until after day 5.”
They had lower viral load:

A larger study in India (306 people) found also found that nitric oxide nasal spray (NONS) makes you test negative sooner:

Patients using the spray had faster improvement in symptoms:

It also looks like nitric oxide makes you less likely to give covid to other people:

Apparently you don’t need to start immediately; the UK trial found benefits even though everyone started 4 or more days after symptoms started.

Products:

Various sprays made by Sanotize:
– VirX in Thailand
– Enovid in Indonesia, Israel, and Bahrain.

Nitric oxide is not listed as an ingredient, but my vague understanding is that some of the ingredients cause your body to make nitric oxide? Some studies do specifically mention Sanotize as a manufacturer of nitric oxide spray so I guess this is right. The Sanotize sprays also contain HPMC (see below.)

Nasal washing (neti pot or various other devices)

From a 2022 review of studies on nasal washing (6 using saline, 3 using povidone iodine, and one using an intranasal corticosteroid):

“Among the 10 RCTs, 8 demonstrated that upper respiratory tract symptoms were reduced with nasal irrigation; 3 revealed a reduction in viral load; 4 reported specifically on viral load reduction in the nasopharynx; and 4 reported on side effects, the most common of which was mild nasal irritation. Only a single study reported data on transmission.”

1 small study (79 people, US) showed that people who started nasal washing with either baking soda (sodium bicarbonate) or povidone iodine and sodium chloride right after testing positive with covid resulted in 8x fewer hospitalizations than you’d expect in this population. No control group so I can’t distinguish this from “people who participate in studies are likely to have milder covid cases for other reasons.” No significant difference between the two types of wash – products used were Neilmed or Navage. 

Extremely rare: in warm areas, there are occasional cases of fatal brain-eating amoebas from nasal washing. Standard advice is to boil the water first (although given how rare the infection is, it’s not clear that using unboiled water is more dangerous than, say, crossing the street.)

Products
Neilmed, Navage, various others.
You can mix your own with table salt and/or baking soda.

Hydroxypropyl methyl cellulose (HPMC) 

HPMC is a polymer approved in the US and EU as a thickening agent in food. If you put it in your nose, it makes a gel that covers nasal receptors and is acidic enough to hinder replication of respiratory viruses. Everything I saw assumes it works for 5 hours.

As far as I can tell, there’s only one published study on humans. This is a cool study design although not randomized: the rabbi encouraged everybody to use this product while praying at a packed two-day Rosh Hashanah service and for two weeks after. It was 2020 and transmission was very high in that community, so they had every reason to expect this to be a superspreader event. None of the people using the product regularly got covid, and 10% of those not using it got covid. (But maybe those people were taking fewer precautions in general – not randomized.)

Products:
– In Israel and Europe it’s sold as Taffix or Enovid
– In the UK as Nasaleze (with several variations but it looks like the “allergy” version has the highest proportion of HPMC and worked slightly better in an in vitro trial). 

Carrageenan

Known for a long time to be antiviral. It’s made from seaweed and is a common food ingredient. As far as I can tell it’s another one that works partly by forming a physical barrier.

Argentine study of 400 hospital workers exposed to covid patients: it reduced risk of catching covid by about 80%.

A 2021 summary of various trials on the common cold:

Products:
UK: Boots dual defence spray
list of products in various countries

Xylitol

Xylitol is a sugar alcohol commonly used in sugarfree gum. It has antimicrobial properties. In vivo tests on respiratory infections don’t seem that great. One small study (30 people) found that xylitol nasal wash worked better than saline wash for treating sinus infections. Another small (42 person) study of people with nonallergic rhinitis (stuffy nose) found xylitol spray helped them feel better.

Product: 
Xlear nasal spray

Saline spray / wash

One small study found saline wash helped people with covid have less nasal symptoms like sneezing and stuffy nose, but didn’t shorten the infection.

In several studies the placebo was saline or wash. Saline is also kinda germicidal, so the effect of the other sprays (compared to no spray) is probably a bit better than it looks in the studies.

I assumed at first that “saline” meant sodium chloride (table salt), but some studies seem to also mean things like bicarbonate of soda (baking soda). Some studies just use a commercial saline wash that doesn’t specify ingredients.

Various mouthwashes

A meta-study on mouthwashes for covid says “hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, cetylpyridinium chloride, β-cyclodextrin-citrox, and sorbitol with xylitol were effective in vivo.” I didn’t look into the details but you can find tem from that metastudy.

Alcohol

Once I started reading about this, I got a lot of ads for nasal alcohol swabs marketed to hospital staff. The research seems to support this for reducing MRSA and other infections in hospitals, but I don’t see research about using it outside that setting.

Zinc

This one is better studied than the others, with multiple randomized trials. Cochrane says “Zinc administered within 24 hours of onset of symptoms reduces the duration of common cold symptoms in healthy people but some caution is needed due to the heterogeneity of the data. As the zinc lozenges formulation has been widely studied and there is a significant reduction in the duration of cold at a dose of ≥ 75 mg/day, for those considering using zinc it would be best to use it at this dose throughout the cold. Regarding prophylactic zinc supplementation, currently no firm recommendation can be made because of insufficient data. When using zinc lozenges (not as syrup or tablets) the likely benefit has to be balanced against side effects, notably a bad taste and nausea. . . .The syrup and tablet preparation of zinc is better tolerated than lozenges.”

I don’t understand if there’s a difference between zinc acetate and zinc gluconate – Cochrane doesn’t seem to think so. I can tell you that the zinc acetate lozenges I have (18 mg) are pretty nasty and it’s hard to imagine consuming 75 mg a day. I would rather have a cold. But if tablets work ok (something you swallow immediately instead of it dissolving in your mouth over 20 minutes), that would be a lot better.

Other stuff being researched but not on the market as far as I know

Supramolecular filaments – Hopkins
Some mix of stuff including xylitol and a bunch of other things – UK/India
Pentosan polysulfate – RPI / Albany
TMPRSS2 – Cornell / Canada

Side effects

In general it seemed like people didn’t mind these products that much, with the exception of zinc lozenges. [Edited to add: when my family got covid, one of my family members hated the feeling of the neti pot and the taste of iodine gargle.] For the others, the most common side effect listed was “unpleasant nasal tingling” or the weird feeling of having fluid in your nose. “Nose too clean” is a real complaint listed in a study.

The only significant side effect I saw was possible thyroid effects from iodine. If I already had a thyroid problem, I would avoid iodine.

None of these studies were on long-term use. It’s common that people using nasal decongestant sprays for more than a few days get rebound congestion – their congestion comes back worse when they don’t use the spray. I’m not sure if the same thing could happen with these. Or it could mess up your nose in some other way, which would be bad because your nose is supposed to filter out germs and other stuff.

What about pregnancy? Breastfeeding? Little kids?

Nitric oxide

Nitric oxide is sometimes used for pregnant or pediatric patients with respiratory distress (because it’s a vasodilator and improves oxygenation). But when someone is already having trouble breathing, that’s a very different cost/benefit situation than what I’m talking about here.

There’s some evidence that nitric oxide in first trimester is related to birth defects.

Carageenan 

Carageenan is already in a lot of baby formulas, and has been “generally recognized as safe” in the US since the 1959. But maybe spraying it in your nose is different.

One study on carageenan nasal spray in children 1-18 with the common cold just says it’s “safe and well tolerated” and caused fewer side effects than the saline placebo. It also seemed to  help kids feel better sooner, and reduce their viral load. The Betadyne spray is the same as the adult one but with a smaller sprayer?

Iodine

Pediatric use of iodine: generally considered safe as an antiseptic, but no data on using it as a nasal spray repeatedly.

Iodine is usually recommended against during pregnancy (except maybe late pregnancy?) because of possible effects on the baby’s thyroid.

Iodine in breastmilk

Best acronym

The Sino-Nasal Outcome Test 20 is abbreviated “SNOT-20.”

Personal takeaways

I have bought a couple of these products and will probably use some of them:
– a spray with carrageenan or HPMC occasionally to reduce chances of catching covid at high-risk events
– carrageenan spray during the early part of a cold
– nasal washing and gargling with iodine during covid. Nasal washing seems like more of a hassle then a spray, but probably works better.