Newsletter #268

Hey friends! As you might imagine, we have been following the research on GLP-1 analogues with great interest. Unfortunately, these drugs are still very difficult to access for millions who would benefit from them, and of course scientists are still figuring out the long-term effects of these medications.

In the meantime, some preliminary research suggests that dietary compounds might be able to modulate hunger hormones and improve appetite regulation (albeit not quite like semaglutide!).

First, a quick bit of plant cell biology. Plants, as I’m sure you already know, rely upon photosynthesis to generate energy. The enzymes that help bring about this process are tucked inside of tiny membrane-bound compartments known as thylakoids. Given their critical role in photosynthesis, you would expect thylakoids to be concentrated in the leaves of plants, and that is indeed the case. In our diet, green leafy vegetables are the best source of thylakoids.

Interestingly, some earlier rodent trials suggested that thylakoids, usually derived from spinach, were linked to weight reduction. For example, female rats on a high-fat diet supplemented with thylakoids for 13 days had lower body mass (–18%) compared to controls, and mice that were fed thylakoids for 100 days experienced an even greater reduction in body weight (–27%). In both cases, this was driven by a significant decrease in food intake.

How come? Well, it probably has to do with how thylakoids behave in the gut, and specifically how these membranes influence fat digestion.

You see, fats get broken down in the intestine by pancreatic lipase and co-lipase. Thylakoids are able to bind to these enzymes, thus slowing down (but not stopping) the digestion of fats. And we have known for decades that when fat lingers in the intestine for a longer time, it promotes the release of various gut hormones that enhance satiety. This effect on lipolysis is temporary — since eventually other enzymes will break down the thylakoids — but the delay is long enough to boost signals in the gut, which go up to the brain and result in appetite regulation.

Or at least, that's what we see in these animal studies. What about in humans? Let’s take a look.

Researchers at Lund University in Sweden recruited 26 women and had them visit the lab on two different occasions, each of which was separated by at least one week. One one visit, they were served breakfast, with 5 grams of thylakoids and on the other day they were given an otherwise identical breakfast with placebo. Then, they filled out questionnaires on an hourly basis that gauged hunger, satiety, and desire for specific foods. Compared to when they consumed placebo, treatment with thylakoids reduced hunger ratings by 21%, and increased ratings of satiety by 14%, and this effect was evident the whole day. Thylakoids also decreased their interest in specific palatable foods, like sweet and salty snacks. Desire for these types of foods dropped by 36%, compared to when they were given placebo. Finally, at the end of each test day, they were presented with a snack buffet, from which each participant could eat as much as they desired. When taking thylakoids, they consumed 11% less compared to placebo (810 calories vs 912 calories on average), however this difference was not statistically significant.

Swedish researchers recruited 11 healthy volunteers and had them visit the lab on six different occasions. During each session, they were presented a pesto sandwich which contained varying amounts of thylakoids extracted from spinach (as well as a control). Blood samples were collected at various points after each meal to measure the effects of the thylakoids on hormones related to appetite regulation. They found, similar to the aforementioned animal studies, that thylakoids resulted in an increased cholecystokinin (CCK) response. Cholecystokinin is a peptide hormone that is secreted in the presence of fats and proteins, and which is known to promote satiety. Thylakoids slow down fat digestion, so it makes sense that CCK is boosted in this manner. On the other hand, serum ghrelin, a hormone associated with greater hunger, was significantly lower two hours after consuming thylakoids. Finally, levels of leptin, a satiety hormone secreted by fat cells, were boosted at the 6 hour mark. All of this, taken together, would be expected to dampen appetite and promote satiety signals in response to food intake.

A group of 38 women were randomly assigned to take either thylakoids (5 g) or placebo once daily before breakfast for 12 weeks, in conjunction with a moderate diet and exercise program. Over the course of the study, they visited the lab periodically to get blood drawn, record their body weight, and respond to questionnaires related to appetite. The supplement resulted in a decreased urge to eat, which was apparent on day 1 and was sustained all the way through to day 90, with no evidence of waning over time. For instance, the women’s interest in chocolate was decreased by 87%, and their desire for sweet foods lowered by 95%. This may have been driven by increased levels of the satiety hormone glucagon like peptide-1 (GLP-1), which was substantially elevated (+44%) in the women treated with thylakoid. After 3 months, both groups lost weight, however supplementation with the spinach extract resulted in 43% greater weight loss than the control group. As the researchers note, “The effect of green-plant membranes on body weight loss (6.3%) after 12 weeks was comparable to the effect of treatment with the GLP-1 analogue liraglutide.”

💪 Spinach is actually not a particularly good source of iron.

In 1870, the iron content of spinach was first determined to be around 35 mg in a 100-gram serving. If that sounds like a lot, you’d be right – this measurement was a huge mistake, on the order of around 10-fold, perhaps due to contamination from lab equipment.

A subsequent analysis decades later revealed it to be false, but the insanely high original value lingered in the popular imagination. Indeed, it has been claimed that this inflated measurement is why animator EC Segar chose spinach as the source of Popeye’s superhuman strength, although this has since been disputed.

Furthermore, the iron in spinach is not well absorbed, although this is probably not due to the presence of oxalates, as some have suggested, but rather due to its high polyphenol content.

Fortunately, there are plenty of other good sources of iron out there.

If you like to make green smoothies (for those spinach thylakoids, or other nutrients), a high-powered blender is basically a must. It’s one of those things that seems extravagant and unnecessary, but once you try it, you’ll never go back to typical countertop blenders. Trust me.

If the price puts you off, you might do what I did and snag a refurbished model, or wait for a flash sale (FYI: premium kitchen appliances are often drastically reduced for Prime Day, which is almost upon us).

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How-to Guide: Smoothies

This week, we’d like to highlight our How-to Guide for Smoothies, because smoothies are an ideal way to introduce more thylakoids into your daily diet.

Here’s why: A typical bag of baby spinach, like you see at the grocery, contains around 3-5 grams of thylakoids. The problem is that consuming thylakoids from unprocessed veggies is inefficient, because thylakoids are tightly locked away inside the cell walls. When the scientists cited above prepare thylakoids, they first put the spinach in a blender to tear it into tiny particles, smaller than your teeth or your digestive system can achieve. This is a good example of how processing can actually enhance the health benefits associated with whole fruits and vegetables.

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