Thread by @DruvBhagavan

You may have heard of the recent spate of hospitalizations linked to Daily Harvest ready-to-eat lentil/leek crumbles.

The exact cause remains a mystery, but several theories are swirling around. I'd like to explore a few of them. (1/n) 🧵⬇️

#ToxTweets #FOAMed #MedTwitter

Anecdotal reports on Twitter and Reddit share common elements. People:

1) Ate the lentil crumbles;

2) Rapidly developed severe stomach pain, dark urine, itchiness;

3) Had symptoms/labs consistent with acute liver failure (ALF) on hospitalization. (2/n)

https://twitter.com/parismartineau/status/1539275464413429761?s=20&t=J3ZKns3QE1-YQltLFS77bA

The product has since been voluntarily recalled, and the FDA is currently investigating potential causes. Most speculation currently centers around a few possibilities:

1) Lectins
2) Aflatoxins
3) Other Pathogens

I'll mainly focus on the first two for this thread. (3/n)

(1) LECTINS

Lectins are a broad category of proteins that bind to specific *carbohydrates* (sugars) attached to proteins. These carbohydrate chains (AKA glycans) are found *everywhere*, and they are highly specific for different organisms. (4/n)

Lectins are found many plants, especially uncooked lentils and beans, and *many* other organisms, which mainly use them to stick things together for a variety of different purposes (AKA agglutination).

This makes them extremely useful in research, too! Some examples:

(5/n)

(A) Wheat Germ Agglutinin (WGA)

WGA is found in wheat kernels and binds strongly to specific carbohydrates, such as GlcNAc & sialic acid.

Add a fluorescent label, and it can be used to label Gram(+) bacteria and beautifully outline cell membranes on immunofluorescence. (6/n)

(B) Blood Typing

RBC antigens (A, B, O, etc.) are actually carbohydrates! We use antibodies to type (ABO) and specific purified plant lectins to cross-match (other antigens) before blood donation or organ transplant (hemagglutination). Getting this wrong can be disastrous. (7/n)

(C) Influenza Hemagglutinin (HA)

Viruses like influenza *also* use lectins (like HA) to bind sialic acid on mammalian cell surfaces (like WGA does) so that they can attach and be internalized to infect the cell.

(Hemagglutinin is the "H" from H1N1, by the way). (8/n)

(D) Mannose-Binding Lectin (MBL)

We also use lectins to fight back against pathogens! MBL is a crucial component of complement (an ancient part of our immune system).

It binds sugars found on the surface of many bacteria, viruses, and fungi to flag them for destruction. (9/n)

Given the broad range of uses organisms find for lectins, it's little surprise that consuming a lot of them can lead to toxicity.

Plant lectins vary from the benign to the lethal (such as ricin, which has been used for assassinations and is considered a biowarfare agent). (10/n)

As an aside, the reason ricin (found in castor beans) is so toxic is that it has two chains (A & B).

RTB (the lectin) binds sialic acid to enter the cell. RTA (the poison) irreversibly inhibits ribosomes, halting all protein synthesis.

Individual chains are not toxic. (11/n)

Plant lectins (like Concanavalin A & Lentil Lectin) are antinutrients (interfere with nutrient uptake) and cause damage in the GI tract.

After uptake, they can localize to the liver and cause an acute immune-mediated hepatitis by T cell overactivation and cytokine storm. (12/n)

Always cook your food properly! Cooking denatures (destroys) the lectins present in these foods, making them safe to eat.

Toxic lectins from undercooked lentils could be the culprit, but I personally think it less likely (you'd need to eat a lot of raw lentils for ALF). (13/n)

(2) AFLATOXINS

Aspergillus is a genus of molds, many of which commonly grow on lentils, grains, and other staple crops (often visible to the naked eye).

While their toxins frequently contaminate food, they can also directly infect humans (farmers are at particular risk). (14/n)

Aspergillus ssp. have several commercial uses:

- Production of citric acid (99%) and enzymes (such as lactase)

- Making medications such as anthraquinone (an antimicrobial)

- Breaking down complex starches in rice to allow fermentation to make sake and other rice wines

(15/n)

Aspergillus ssp. produce aflatoxins, which can cause hepatic necrosis (acute) and cirrhosis (chronic). Children are particularly vulnerable! There is no direct cure; only supportive therapy.

Aflatoxins are DNA alkylating agents, so they can also cause liver cancer! (16/n)

In addition to plant products, aflatoxins have been found in milk, eggs, and meat from animals that have eaten (seasonally) contaminated livestock feed.

While unlikely to cause acute toxicity, chronic exposure can increase the risk for cancer! (17/n)
sciencedirect.com/science/articl…

Personally, I think aflatoxin contamination is the most likely cause of the symptoms that those eating the lentil/leek crumbles experienced.

In fact, mycotoxins are frequently found in ready-to-eat foods (though often within acceptable limits)! (18/n)
ncbi.nlm.nih.gov/pmc/articles/P…

(3) OTHER PATHOGENS

Other potential causes of ALF include contamination with Hepatitis A, Salmonella typhi (typhus), and other pathogens.

However, many patients tested negative for Hepatitis A-E antigens, and S. typhi hepatitis is rare, so I think these are less likely. (19/n)

SUMMARY (1):

- Lectins are a broad class of ubiquitous highly-specific carbohydrate-binding proteins.

- Plant lectins found in undercooked lentils/legumes can be highly toxic.

- Cooking lentils/beans properly inactivates any lectins present, making them safe to eat.

(20/n)

SUMMARY (2):

- Aspergillus ssp. frequently contaminate staple crops but have commercial uses.

- Aflatoxins, produced by these molds, are often found in contaminated ready-to-eat foods.

- Other pathogens (Hep A, S. typhi) are possible ALF culprits (but less likely).

(21/n)

KEY TAKEAWAYS:

🔑 Cook lentils and beans thoroughly before eating.
🔑 Check all foods for visible mold/fungus growth before consumption.
🔑 Wash hands thoroughly to prevent the spread of pathogens like Hep A and S. typhi.
🔑 Report suspected food contaminants to the FDA.

(22/n)

You can report suspected contaminated food or other problems to the FDA at the link below!

Make sure to seal the products in question and keep away from other food or places accessible by pets or small children. The FDA may request a sample. (23/n)
fda.gov/safety/report-…

Sources and additional information can be found in the alt text of figures.

Excellent people to follow for more toxicology, immunology, and product/supplement safety: Dr. @jtrebach (just don't follow him onto a plane), Dr. @RyanMarino, @ENirenberg, and Dr. @Neurofourier! (24/25)

Oh, and if you'd like, you can follow me as well, I suppose (especially if you found this thread interesting or informative)! I plan to post more #FOAMed threads and figures in the future.

I hope that everyone affected makes a full recovery. Until next time! 🙂

(25/25) (FIN 🧵)

It seems as though my intended alt text for the first two images did not make it into the thread. Reposting them here with the alt text added for accessibility: