Whey Protein, Breast Milk, and COVID-19

August 20, 2020

In a preprint* released today, researchers from China provided evidence that human breast milk, and to a lesser extent milk and whey protein from cows and goats, inhibits the replication of a “pseudovirus” model of SARS-CoV-2, the coronavirus that causes COVID-19. These results raise the possibility that the protective properties of breast milk would prevent a mother from transmitting the virus to her baby, and that supplementation with whey protein could provide some protection against COVID-19.

On June 8, I had reported on a paper showing that lactoferrin inhibits the replication of SARS-CoV-2, the coronavirus that causes COVID-19, in isolated cells. I discussed the ability of lactoferrin to lower IL-6, and noted that apart from one source in Italy, the best way to obtain lactoferrin is to consume between 20 and 40 grams of whey protein per day.

Today's paper adds to the reasons to favor the whey protein approach.

How The Study Was Done

The researchers who released today's paper used a “pseudovirus” instead of authentic SARS-CoV-2 because the pseudovirus can be studied with much less restrictive laboratory procedures, and in labs that do not have the special infrastructure requirements needed to handle more dangerous pathogens (for details, see the differences between biosafety levels 2 and 3 here). The pseudovirus combined the spike protein of SARS-CoV-2, which is what it uses to attach and infect human cells, with an enveloped virus that infects insects and farm animals. That pseudovirus has been shown to respond similarly to SARS-CoV-2 in response to neutralizing antibodies, so might act as a good model for the SARS-CoV-2 response to other antivirals as well.

They confirmed their findings using a natural coronavirus related to SARS-CoV-2 that infects pangolins instead of humans. Pangolins are mammals that look like anteaters, but with scales, and are native to Africa and Asia.

They performed the experiments in isolated cells ultimately derived from the kidneys of African green monkeys and from human lung cancer tissue.

Human, Cow, and Goat Milk Inhibit Viral Replication

Incubating the cells with 4 milligrams per milliliter (that is, 0.4% concentration) of human milk inhibited viral replication by 98%.

The concentration of human breast milk required to yield 50% inhibition ranged from 0.34 to 0.79 mg/mL (that is, 0.034% to 0.079%) using milk from different donors. However, it was all under 0.1 mg/mL (0.01%).

Bovine milk was 79% as effective as human milk, and goat milk was 73% as effective.

The Role of Lactoferrin

Then they compared different lactoferrins to human milk, all at a concentration of 1 mg/mL:

• Recombinant lactoferrin, which is isolated from rice that is genetically engineered to make human lactoferrin, was only 8% as effective as human milk.

• Bovine lactoferrin was 15% as effective as human milk.

• Natural human lactoferrin was 46% as effective as human milk.

Put another way, natural human lactoferrin was almost six times more effective than genetically engineered human lactoferrin, and three times more effective than bovine lactoferrin, but human milk was more than twice as effective as human lactoferrin.

Notably, if we compare the experiment testing the different lactoferrins to the one testing the different milks, bovine milk is 5.3 times more effective than bovine lactoferrin, while human milk is only 2.2 times as effective as lactoferrin. This suggests to me that lactoferrin plays a much more important role in the protective effect of human milk than it does in the protective effect of bovine milk. However, in both milks, there is clearly more to the story than lactoferrin.

No Role for Non-Specific IgA Antibodies

IgA antibodies are part of the antimicrobial defense of human milk. To test whether IgA antibodies contributed to the protective effect of human milk, they included different concentrations of antibodies directed against human IgA to disrupt their function. This had no impact on the protective effect of breast milk. The breast milk was taken from donors in 2017, so they didn't have any IgA specific to SARS-CoV-2.

Therefore, this does not rule out the protective effects of specific IgA within human milk directed at SARS-CoV-2 from mothers that have recently been infected. However, it does rule out the general benefit of total IgA in the milk of non-infected mothers. Recently infected mothers perhaps have additional protection within their breastmilk from virus-specific IgA.

The Role of Whey Proteins

On the other hand, heating the milk to 90 degrees Celsius for 10 minutes, which destroys whey proteins, destroyed about 75% of the protective effect of the milk. The same thing was achieved through enzymatic destruction of the whey protein. This suggests that whey proteins (one of which is lactoferrin) provide the vast majority of the protective effects of milk.

Notably, this was much more heat damage than would occur during high-temperature, short-time pasteurization, which is typically 72C for 15 seconds. However, it is possible that the cow and goat milk were pasteurized, and that this is why they were somewhat less effective than the human milk. The paper does not say anything about what milk samples were and were not pasteurized.

Comparing The Two Studies

The paper I covered on June 8 suggested that bovine lactoferrin was much more powerful than this study suggests. It reduced SARS-CoV-2 replication by 54% in the same exact cell type using the exact same concentrations studied in this paper, while this paper suggested it only inhibited replication by 15% or less. However, the June 8 paper looked at the replication over three days, while today's paper looked at the effect over 1 day.

It may be the case that bovine lactoferrin inhibits replication by 15% or less over the course of the first day and takes three days of incubation to reach 54% inhibition. Meanwhile, human milk achieves almost complete inhibition within a day.

One other difference is that the first study used authentic SARS-C0V-2, while this study used a pseudovirus designed to model SARS-CoV-2. However, the difference in the effect of bovine lactoferrin can easily be explained by the difference in the duration of the experiments, so the results actually seem very consistent with one another.

Limitations of This Approach

We should always be very cautious about generalizing from an experiment in isolated cells to the effect we would expect in live human beings.

In particular, these proteins will all undergo digestion that could impact their ability to inhibit viral replication in the nose, throat, lungs, or other organs outside the intestines. However, digestion of whey proteins is not complete. Valuable peptides survive digestion, and these include fragments that boost glutathione synthesis (glutathione is antiviral and helps relieve respiratory distress). Under some conditions (described in my previous post) lactoferrin may survive digestion, and either the intact lactoferrin or specific fragments of it lower interleukin-6 (IL-6) levels, which would be expected to improve COVID-19 outcomes.

Therefore, we should not assume that inhibition of viral replication within isolated cells will inhibit viral replication in live humans, but we certainly can't rule it out and it deserves to be tested. Furthermore, consuming lactoferrin or whey protein is harmless for most people, so there is little cost in trying it.

We should also be cautious in drawing firm conclusions from this study because it didn't use authentic SARS-CoV-2. The pseudovirus may behave similarly in response to antibodies, but that doesn't mean it behaves similarly in response to everything else.

Which to Use: Lactoferrin, Whey Protein, or Milk?

As I noted in the June 8 report, the lactoferrin used to lower IL-6 has iron included in 20-30% of its binding sites, which protects it from digestion, and most other lactoferrin supplements on the market do not contain iron. The lactoferrin used to lower IL-6 is only sold from Italy. It is not clear whether other lactoferrin products on the market would be effective at lowering IL-6.

Today's paper shows that lactoferrin only accounts for 19% of the antiviral effect of cow milk, whereas the total whey proteins (including lactoferrin) are responsible for 75% of the effect.

As I noted in the June 8 report, 20-40 grams of whey protein provide approximately the dose of lactoferrin used to lower IL-6, and 15-20% of its binding sites are occupied by iron, making it much closer to the form used to lower IL-6 than to the form available in most commercial supplements. This makes whey protein a better way to obtain lactoferrin than lactoferrin supplements for anyone who does not have access to the Italian product. Today's paper suggests whey protein is the better option for anyone, since it is roughly four times more antiviral than lactoferrin alone.

What about milk?

On the one hand, 25% of the antiviral effect of milk cannot be explained by its whey protein content. There is clearly more to milk than the whey proteins.

On the other hand, it isn't clear what is responsible for that additional 25% or whether any of it survives digestion. One thing that is clear is that it would be very difficult to get an anti-inflammatory dose of lactoferrin from drinking milk. That dose is found in 20-40 grams of whey protein. But milk protein is only 20% whey protein. There is 8 grams of milk protein per cup. As I've written before, pasteurization decreases the whey protein fraction of milk by 30% while ultra-high-temperature (UHT) treatment and sterilization decrease the whey fraction by 80-87%. A cup of non-UHT pasteurized milk probably has around 1.6 grams of whey protein while raw milk probably has around 2.3 grams. While these differences are very likely to be physiologically important from the perspective of boosting glutathione status (see here), neither pasteurized nor raw milk will provide anywhere near the dose of lactoferrin shown to lower IL-6.

Therefore, my present stance is that 20-40 grams of whey protein captures the best of all worlds. However, it is possible that some combination of iron-saturated lactoferrin and pasteurized (weaker) or unpasteurized (stronger) milk could perform as well or better.

The Bottom Line

This study doesn't show that mothers cannot transmit SARS-CoV-2 to their babies through breast milk, but it provides a strong reason to doubt such transmission happens: the breast milk itself is likely to be antiviral. If 0.4% breast milk inhibits 98% of viral replication, how much replication happens when the virus is diluted in 100% breast milk?

20-40 grams of whey protein per day is the simplest and most reliable way to get glutathione-boosting proteins, iron-saturated lactoferrin, and the remaining unknown antiviral properties of whey protein. However, it remains to be seen whether these results fully translate into antiviral effects in live humans, and this approach fails to capture 25% of the total antiviral activity of milk. Therefore, milk itself may have the broadest spectrum of antivirals, while whey protein is the best way to get a concentrated dose of the major fraction of those antivirals. Its glutathione-boosting properties may also help with respiratory distress.

I just released version 5 of The Food and Supplement Guide for the Coronavirus three days ago. Version 5 adds to the previous protocol glutathione, vitamin K, and a guide to assessing your risk level and adjusting the protocol to fit that risk level in a way that helps manage costs and prevents long-term nutritional imbalances. Currently, whey protein is not quite ready to be added to the protocol. As much as I see it as a potentially useful, nearly entirely harmless, supplemental practice, too much is unknown about how to set the correct dose to achieve the proper concentrations within our bodies of the relevant antiviral compounds. I will be watching closely for additional evidence, and I am poised to add it to future versions of the guide if these issues become clearer.

In the mean time, I consider it harmless and potentially useful to add 20-40 grams of whey protein to your diet, double-down on your healthiest milk-drinking habit, or supplement with 200 milligrams per day of an iron-saturated lactoferrin if you have access to one.

Stay safe and healthy,
Chris

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*Footnotes

*  The term “preprint” is often used in these updates. Preprints are studies destined for peer-reviewed journals that have yet to be peer-reviewed. Because COVID-19 is such a rapidly evolving disease and peer-review takes so long, most of the information circulating about the disease comes from preprints.