Newsletter #026: The surprising ways diet, hormones, and vitamins affect brain health and longevity 🥗
Good day friends!
Another Saturday has arrived, and so too has the latest HumanOS newsletter! We hope everyone had a safe and happy Halloween. 👻
This Week’s Research Highlights
🥗 A ketogenic diet may enhance blood supply to the brain and potentially prevents Alzheimer's disease.
Researchers fed young healthy mice (12-14 weeks old) a ketogenic diet. After 16 weeks, the mice showed significant increases in cerebral blood flow, which were accompanied by increases in a protein that helps shuttle amyloid beta out of the brain. These neurovascular improvements were associated with lower mTOR and higher endothelial nitric oxide synthase (eNOS) protein expression. Finally, the diet also resulted in improvements in the composition of the gut microbiomes of these animals. The rodents fed the ketogenic diet showed increased relative abundance of beneficial taxa (Akkermansia muciniphila and Lactobacillus), and lower levels of pro-inflammatory taxa (Desulfovibrio and Turicibacter).
Researchers at Columbia University previously demonstrated that a deficiency of the RbAp48 protein in the brain is a significant contributor to age-related memory loss (but not to Alzheimer's disease). More recently, they performed a series of molecular and behavioral experiments in rodent models examining how this protein regulates memory-related circuits in the brain. They found that RbAp48 controls the expression of BDNF and GPR158 proteins, both of which are critical components of osteocalcin signaling in the mouse hippocampus. Inhibition of RbAp48 in the hippocampus inhibits osteocalcin's beneficial functions in cognition and causes deficits in discrimination memory. This lines up with a prior experiment showing that infusions of osteocalcin had a positive impact on memory. Osteocalcin is a hormone released by bone cells in response to exercise. Overall, this study sheds light on underlying mechanisms in the known association between exercise and memory.
🏃 Better cardiorespiratory fitness is associated with a longer lifespan - with the greatest benefits for extremely fit individuals.
Researchers at the Cleveland Clinic retrospectively studied 122,007 patients who had undergone treadmill stress tests at the Clinic, and who were followed for 8.4 years on average. Participants were divided into five performance groups — elite, high, above average, below average and low. Elite performers were defined as having aerobic fitness in the top 2.5% by age and gender, demonstrating fitness levels comparable to endurance athletes. Unsurprisingly, the elite performers were the least likely to die during the study period. Compared to those with low fitness, participants in the elite fitness category had an 80% reduction in all-cause mortality. Elite performers also fared better even compared to high performers (75th-97.6th percentile of aerobic fitness), although the survival benefit was most notable in older patients and those with hypertension. In those over the age of 70, being in the elite fitness group, as opposed to high fitness, was associated with a 30% reduced risk of mortality. Similarly, for those with hypertension, the elite fitness group had a 30% lower risk of all-cause mortality compared to the high fitness group. As the researchers summarize, "Cardiorespiratory fitness is inversely associated with long-term mortality with no observed upper limit of benefit.”
Researchers affiliated with Virginia Commonwealth University analyzed data on serum vitamin D levels and VO2 max from a representative sample of 1995 American adults. Participants were divided into four groups based on vitamin D levels. Participants in the highest quartile of serum vitamin D had 4.3-fold higher cardiorespiratory fitness, compared to those those in the bottom quartile. After adjusting for other relevant factors, like age, BMI, and co-morbidities, the researchers found that the link remained significant, with a 2.9-fold difference in cardiorespiratory fitness in the highest quartile. Furthermore, the researchers found a dose-response relationship between vitamin D and exercise capacity: each 10 nmol/L increase in vitamin D was linked to a 0.78 mL/kg/min increase in VO2 max.
Podcasts We Loved This Week
- Steve Anton: Diet, exercise, intermittent fasting, and lifestyle interventions to improve health. Via STEM-Talk.
- Richard E. Nisbett: Cognitive Fallacies. Via Smart Drug Smarts.
Products We Are Enjoying
Dan says: We know that dark chocolate can be good for you - we’ve written previously about how flavanols in cocoa might improve athletic performance, and even brain function. But all chocolate is not created equal. Most chocolate products contain relatively little flavanols and instead are heavy in milk and sugar. Not great. And this is a particularly big drawback if you follow a ketogenic diet! That’s why I’m glad I stumbled upon these bars. One ounce contains 15 carbs - of which 13 are comprised of dietary fiber - and is mostly just stone-ground cocoa beans.