Orange juice (OJ) as therapy for all coronaviruses, including SARS-CoV-2

haidut

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If anybody needs a reason to convince themselves (or their family members) that drinking OJ is beneficial, maybe this new study in the context of COVID-19 will be good enough as evidence. It demonstrated that one of the main components of OJ - naringenin - is a powerful inhibitor of viral replication and it also has the ability to reduce viral entry into the cells. Peat also mentioned in several of his articles that chemicals in OJ such as naringenin are responsible for the majority of its beneficial effects. Considering naringenin also has strong anti-inflammatory properties, it may also be suitable for reducing the risk of COVID-19 exacerbations, which have demonstrated to be essentially nothing more than a systemic inflammatory syndrome. A few lesser known beneficial properties of naringenin are its anti-estrogenic and progestogenic effects. In fact, naringenin (together with apigenin) is one of the few well-known phytoprogestogens. Progestogenic and/or anti-estrogenic chemicals have already been confirmed as therapeutic for viral infections, possibly including COVID-19 as well. Even more interestingly, the study below suggests that naringenin may be a universal treatment for ALL types of coronavirus infections. As such, if SARS-CoV-2 were to mutate or we get hit by another coronavirus pandemic, naringenin should still be therapeutic.

Naringenin is a powerful inhibitor of SARS-CoV-2 infection in vitro
"...On the whole, Nar behaves as a lysosomotropic active natural compound exhibiting human pan-CoV antiviral activity. Interestingly, besides its antiviral power, Nar has anti-inflammatory activity by inhibiting TNF-α and IL-6 secretion [15] which may synergistically enhance its antiviral effect in vivo. The potential of possible Nar-based medical treatment is that it could tackle both viral infection and the cytokine release/cytokine storm syndrome in COVID-19. As regards clinical trials, the therapeutic potential and safety of Nar have been reviewed [16] and a more recent clinical trial on the pharmacokinetics and metabolism of Nar indicates this compound as a very promising candidate for clinical applications [17]. In particular, it has been reported that in healthy humans an oral dose of 600 mg Nar results in a serum Cmax of about 50 μM, whithout relevant toxicity [18]. Interestingly, this dosage could approach the threshold to ameliorate the cytokine storm as well as inhibit the activity of TPCs. The use of Nar, a hydrophobic molecule able to cross biological membranes and to reach intracellular compartments, as a specific inhibitor of TPCs [4,5] provides further support for exploiting TPCs inhibition as a novel antiviral therapy. In our view, optimal Nar therapeutic delivery would require nanotechnological approaches and targeting the drug directly to the upper respiratory airways, a non-invasive method of administration, which would warrant direct and selective access at the sites most susceptible to SARS-CoV-2 infection, given the gradient of infectivity reported in the respiratory tree [19]. In conclusion, data presented in this work point to Nar as a safe anti-SARS-CoV-2 agent endowed with pan-coronavirus inhibitory activity. These findings offer a potential molecular model for CoV infection and a candidate drug target for further, in vivo, experimental trials aimed at improving the management of COVID-19 patients."
 

haidut

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Nice.

@haidut Do you know how much orange juice per day this may boil down to?

I think a glass has about 150mg naringin, which probably provides about 100mg naringenin. So, 2-3 glasses a day should be enough to replicate the study design.
 

Comstock

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I think a glass has about 150mg naringin, which probably provides about 100mg naringenin. So, 2-3 glasses a day should be enough to replicate the study design.
That's awesome, it's a very reasonable amount. Explains why I barely get the sniffles anymore.
 

Mauritio

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The question is:" how much OJ do you have to drink to get a sufficient level of naringenin ?"

The study haidut posted says the following :

"In particular, it has been reported that in healthy humans an oral dose of 600 mg Nar results in a serum Cmax of about 50 μM, whithout relevant toxicity [18]. Interestingly, this dosage could approach the threshold to ameliorate the cytokine storm as well as inhibit the activity of TPCs. "

So 600mg to only approach the realm where it could be useful.


This study found that :
"Naringin, naringenin, and poncirin showed lower concentration levels in the orange juices; the average contents and concentration ranges found were 0.019 and 0.01–0.30, 0.12 and 0.1–0.17, and 0.13 and 0.01–0.36 mg 100 g−1, respectively.

So 0.12-0.17 mg/100g .
1 liter per day averages only 120-170mg . To get to the 600mg threshold you'd have to drink 4 liters of OJ .
I for example can't stomach much more than 1 maybe 2 glasses of commercial OJ .
So maybe at this point a supplement makes more sense .
 

ronin570

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I think you can eat the orange peel for naringinen. Maybe marmalade is a nice food to add
 

mrchibbs

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So 0.12-0.17 mg/100g .
1 liter per day averages only 120-170mg . To get to the 600mg threshold you'd have to drink 4 liters of OJ .
I for example can't stomach much more than 1 maybe 2 glasses of commercial OJ .
So maybe at this point a supplement makes more sense .

I think this highlights the importance of complementing the OJ with homemade marmalade made with oranges, but also grapefruit which have more naringin.

As far as I can gather from the research, mandarin oranges have by far, the highest concentration of naringin, so if you can find those to make marmalade with, even better.

And of course, adding a powdered naringin supplement to the mix won't hurt.
 

haidut

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The question is:" how much OJ do you have to drink to get a sufficient level of naringenin ?"

The study haidut posted says the following :

"In particular, it has been reported that in healthy humans an oral dose of 600 mg Nar results in a serum Cmax of about 50 μM, whithout relevant toxicity [18]. Interestingly, this dosage could approach the threshold to ameliorate the cytokine storm as well as inhibit the activity of TPCs. "

So 600mg to only approach the realm where it could be useful.


This study found that :
"Naringin, naringenin, and poncirin showed lower concentration levels in the orange juices; the average contents and concentration ranges found were 0.019 and 0.01–0.30, 0.12 and 0.1–0.17, and 0.13 and 0.01–0.36 mg 100 g−1, respectively.

So 0.12-0.17 mg/100g .
1 liter per day averages only 120-170mg . To get to the 600mg threshold you'd have to drink 4 liters of OJ .
I for example can't stomach much more than 1 maybe 2 glasses of commercial OJ .
So maybe at this point a supplement makes more sense .

Naringin converts into naringenin, so you can more or less add their numbers and you get 220mg-340mg per liter. There are also a number of other related nutrients in OJ that have almost the same structure and effects - apigenin, fisetin, and a few others. There is an old study that I need to find that found drinking a glass of OJ provided several hundred milligrams of flavanoids as measured by urine and fecal excretion. So, 2-3 glasses of OJ may be enough.
Also, if you look inside the study they show that 62.5 uM / L concentration of naringenin resulted in 100% infection inhibition. However, the IC50 was less than 31.3 uM / L. They also measured beneficial effects from a single naringenin treatment only. When drinking OJ daily you'd still get the benefits even from lower naringenin concentrations, and due to much longer exposure to the chemical (due to chronic ingestion). So, while complete viral blockade may require a supplement, drinking OJ on a daily basis seems like a great way to prevent COVID-19, and may be even treat it as chronic naringenin exposure will likely prevent the more severe forms of the disease that require hospitalization, intubation, etc.
Just my 2c.
 

Mauritio

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Naringin converts into naringenin, so you can more or less add their numbers and you get 220mg-340mg per liter. There are also a number of other related nutrients in OJ that have almost the same structure and effects - apigenin, fisetin, and a few others. There is an old study that I need to find that found drinking a glass of OJ provided several hundred milligrams of flavanoids as measured by urine and fecal excretion. So, 2-3 glasses of OJ may be enough.
Also, if you look inside the study they show that 62.5 uM / L concentration of naringenin resulted in 100% infection inhibition. However, the IC50 was less than 31.3 uM / L. They also measured beneficial effects from a single naringenin treatment only. When drinking OJ daily you'd still get the benefits even from lower naringenin concentrations, and due to much longer exposure to the chemical (due to chronic ingestion). So, while complete viral blockade may require a supplement, drinking OJ on a daily basis seems like a great way to prevent COVID-19, and may be even treat it as chronic naringenin exposure will likely prevent the more severe forms of the disease that require hospitalization, intubation, etc.
Just my 2c.
Ok cool .
 

Amazoniac

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Not needing a complete inhibition for it to be helpful, the synergistic components and the cooperation by the immune system are fair points, yet keeping cells steadily bathed in the therapeutic range with orange juice is a challenge. I'm finding different flavonode concentrations reported, it's almost as if it was a natural product that's subject to variations.

- Plasma Kinetics and Urinary Excretion of the Flavanones Naringenin and Hesperetin in Humans after Ingestion of Orange Juice and Grapefruit Juice

"In both studies, the amount of ingested juice was 8 mL/kg. The ingested amounts ranged between 400 and 760 mL of orange juice and between 400 and 720 mL of grapefruit juice. The subjects ingested the juice within 7 min at the study site in the morning after an overnight fast. The subjects were allowed to eat for the first time 4 h after ingestion of the test juice."​
"The concentrations of naringenin and hesperetin in the orange juice were 151 μmol/L (41 mg/L) and 722 μmol/L (218 mg/L), respectively. The concentration of naringenin in the grapefruit juice was 1283 μmol/L (349 mg/L)."​
"The Cmax values were 0.1–1.2 μmol/L for naringenin from orange juice and 0.7–14.8 μmol/L for naringenin from grapefruit juice."​

Check out figure 2, for people drinking about 0.5 L of orange juice, no one had a circulating concentration greater than 1.2 μmol/L, and that's the peak, most of the time it was well below.

Reaching that range is easier with grapefruit juice, but there are the issues with it.


Only about half of the naringid molecule has the potential to liberate naringenid (they isn't interchangeable), the rest should be responsible for the bitter taste and I think that people would avoid bitter juices in large amounts, it may be taxing for us to be able to detect the taste, this may get in the way of renewing the dose.

From Mauritio's link:


For a combination of compounds, there are other foods that might be just as effective and not heavily contaminated with viric acid given the recurrent claims that it promotes viral infections and is overall detrimental. Any benefit being in spite of the virate content (which is what characterizes such fruits) is something as questionable as suggesting that caffeine is only an inconvenient in the coffea class of foods, and in case it's considered harmful, that the rest of the components are worth the exposure to what sets them aside from other foods without weighing them.

To stick to the idea would require prioritizing alternative sources that contain antivirals while being low in provirals. At 10 g VA/L orange juice, it rapidly leads to frank viremia, the other elements only functioning as retardants. Not that there isn't anything to his assertion, but I always had the impression that how Raj tried to backup his observation was arbitrary, he could've contracted a STD in a Mexican alley while drinking jugo de limon and blame an extreme reaction on the beverage. What about the traditional lime and honey flu recipe?
 

jmojo

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David90

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Naringin converts into naringenin, so you can more or less add their numbers and you get 220mg-340mg per liter. There are also a number of other related nutrients in OJ that have almost the same structure and effects - apigenin, fisetin, and a few others. There is an old study that I need to find that found drinking a glass of OJ provided several hundred milligrams of flavanoids as measured by urine and fecal excretion. So, 2-3 glasses of OJ may be enough.
Also, if you look inside the study they show that 62.5 uM / L concentration of naringenin resulted in 100% infection inhibition. However, the IC50 was less than 31.3 uM / L. They also measured beneficial effects from a single naringenin treatment only. When drinking OJ daily you'd still get the benefits even from lower naringenin concentrations, and due to much longer exposure to the chemical (due to chronic ingestion). So, while complete viral blockade may require a supplement, drinking OJ on a daily basis seems like a great way to prevent COVID-19, and may be even treat it as chronic naringenin exposure will likely prevent the more severe forms of the disease that require hospitalization, intubation, etc.
Just my 2c.
Nice. One More Reason to Drink more OJ. I surely will :D
 
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