Newsletter #223

Recently, a study that followed seventeen astronauts found that spaceflight results in a profound loss of bone strength, equivalent to more than a decade of age-related bone loss. And it had an enduring impact - about half of the participants failed to fully recover bone mineral density (BMD) after 12 months back on Earth, despite exercise regimens intended to preserve bone health.

This made me really appreciate how important taking care of our bones is (as the friendly folks at r/neverbrokeabone will more than happily remind you). But it also caused me to wonder to what extent dietary factors might also play a role in bone density. Most of us know that various nutrients play a role in bone remodeling, like calcium, magnesium, vitamin D, etc. But some research also suggests that phytochemicals, such as flavonoids, in specific foods may also be beneficial. To understand why, you need to know a little bit about how bones work.

Bone is in a constant state of remodeling, which is important for the maintenance of normal skeletal structure and function. The two main cells involved in this process are osteoblasts and osteoclasts, and they perform opposing functions. Osteoblasts are responsible for new bone formation, while osteoclasts are involved with bone resorption, meaning that they break down the tissue in bones and release the minerals into circulation.

In normal bone homeostasis, the osteoblasts secrete something called receptor activator of nuclear factor kappa-Β ligand (RANKL for short). RANKL’s job is to bind to RANK on osteoclast precursors, which go on to form the osteoclasts that break down bone. Now, this isn’t necessarily a bad thing, because much like muscle, bone tissue undergoes wear and tear over time and needs to be broken down and rebuilt. But you don’t want a whole lot of bone resorption at the expense of bone building, which is what can happen if RANKL gets activated too much.

Various molecules can modulate this process, for better and for worse, and if you look at the graphic above you can see how the various players get involved. Pro-inflammatory cytokines, reactive oxygen species (ROS), and several types of immune cells all stimulate RANKL. This potentially leads to greater bone resorption, and ultimately to bone loss. No bueno. Estrogen, in contrast, suppresses RANKL through multiple pathways, which is why estrogen deficiency tends to lead to osteoporosis.

So if we put this all together, you can see that fighting oxidative stress and inflammation would be expected to help tilt the balance a little more toward bone formation and away from bone resorption. And indeed, this is likely why several flavonoid-rich foodsseem to have beneficial effects on bone health.

Preclinical animal research has shown that supplementation with tea polyphenols is associated with improvements in measures of bone health. To examine the effects of tea in a human population, researchers in Western Australia analyzed data from 1027 older women (aged 70-85) who had participated in a 5-year prospective trial looking at whether calcium supplementation prevented fractures. The researchers found that total hip bone mineral density was 2.8% greater in tea drinkers than in non-tea drinkers. Then, the researchers performed a prospective analysis of data from a subgroup of 164 of the women. They followed how tea intake at baseline was correlated with changes in bone mineral density (BMD) from year 1 to year 5. They found that the tea drinkers still experienced bone loss, but much less than non-tea drinking counterparts (-1.6% total hip BMD vs -4.0% total hip BMD). This finding lines up with more recent meta-analyses of observational studies, which have found that tea consumption is linked to both increased BMD and decreased risk of osteoporosis. This has been attributed to favorable effects of tea flavonoids, like epigallocatechin and epicatechin, on inflammation and oxidative stress.

Prior short-term trials have shown that consuming prunes results in increases in markers of bone formation as well as reductions in markers of bone resorption. To explore the long-term effects of prunes on bone density, Researchers at Penn State recruited 235 women (mean age of 62) and randomly allocated them into three groups: Control, 50 g prune, or 100 g prune. The two experimental groups consumed the assigned amount of prunes daily for 12 months. After one year, total hip BMD decreased -1.1 ± 0.2% in the Control group, while the 50 g Prune group preserved BMD at 12 months. Furthermore, the control group showed a 10% increase in their calculated 10-year hip fracture risk (FRAX), but both prune groups maintained the same FRAX score as they had at baseline. It is thought that the dietary fiber and polyphenols in prunes may alter the composition of the gut microbiota, boosting production of short-chain fatty acids. Higher levels of these metabolites are linked to pro-inflammatory cytokines, which would be expected to decrease bone resorption.

Researchers in Norway had previously found that daily intake of Jarlsberg cheese, a mild “Swiss-type” cheese, led to increased serum osteocalcin. Osteocalcin is a hormone produced by osteoblasts. As such, it is often used as a marker for bone formation; higher serum osteocalcin is correlated with increases in BMD. The Norwegian scientists wanted to know whether this was an effect generalizable to other cheeses, or if it was specific to this variety. To that end, they recruited 66 healthy female volunteers and randomly split them into two groups. One group was assigned to consume 57g of Jarlsberg daily, and the other to 50 g of Camembert daily for 6 weeks. Then, both groups were swapped to the opposite cheese for another 6 weeks, so that they could see how both cheeses affected each individual participant.

When participants consumed Jarlsberg, levels of osteocalcin increased significantly, mirroring the previous research, but were slightly reduced when they ate Camembert. Additionally, levels of vitamin K2 rose significantly in the Jarlsberg group, but not in the Camembert, and it is very likely that this is what differentiates Jarlsberg from other cheeses. Jarlsberg contains significant amounts of vitamin K2, because it is generated by bacteria used in the production of this cheese. Vitamin K2 is thought to help transport calcium and magnesium from blood into bones, and indeed, serum levels of calcium and magnesium were lower when the subjects ate Jarlsberg. As an added bonus, participants in the Jarlsberg group experienced a 3% reduction in their HbA1c, which could be attributed to osteocalcin as well, since this hormone also regulates glucose metabolism.

🐋  Somewhere in the Pacific Ocean, there is an individual whale (known as 52 Blue) that calls at its very own frequency.

This week, we’d like to highlight one of the courses from the Ideal Weight Program, developed by our good friend Stephan Guyenet, a researcher who specializes in the neuroscience of eating behavior and obesity. The Ideal Weight Program is an evidence-based system for sustainable weight management which teaches you the science of body weight regulation and eating behavior and translates it into simple, practical strategies for weight management. This program offers three different diets based on your weight management goal. For those who need to lose body fat relatively rapidly (but safely), the FLASH Diet is the plan for you.

FLASH stands for Fat Loss And Sustainable Health, and is modeled after protein-sparing modified fast diets that were developed by researchers in the 1970s and remain the most effective fat loss plan ever studied. In this course, Stephan explains the background behind FLASH diet, where it fits in the sequence of the Ideal Weight Program, what to eat and how to prepare food to adhere to this plan, and more.

Thanks for reading, enjoy the weekend, and we'll see y'all next week!

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