Fighting Advanced Glycation End Products 🧯
Hey guys, after a multi-year hiatus, we are psyched to herald the return of humanOS Radio! As I am sure y’all understand all too well, the pandemic was a major disruption for us like everyone else, and the podcast was an unfortunate casualty of that. But we heard from a bunch of you saying that you missed the show, and that was a major part of what inspired us to bring it back.
Obviously, we share a ton of studies here and on social media, and we’re hyped to get a chance to gain some deeper insight directly from some of the researchers who actually do the hard work in the lab bringing those findings to us in the first place.
So this week, we talked to Professor Kapahi from the Buck Institute about a new product he has developed to help block the formation of advanced glycation end products (AGEs). AGEs are compounds that are formed when proteins or lipids become glycated, as a result of being exposed to sugars, and have been linked to a host of chronic diseases. We also went ahead and highlighted some other tactics for reducing your exposure to AGEs, and the health payoff associated with them.
New humanOS Content
On the first new episode of humanOS Radio in more than two years (!), we welcome Pankaj Kapahi back to the show. Pankaj is a professor at the Buck Institute, an independent biomedical research institute that is devoted solely to research on aging.
we discussed his investigation into the role of AGEs in health and disease. Since then, he has been hard at work trying to figure out ways to battle AGEs. To that end, he has identified a combination of five compounds that show synergistic protective effects against AGE precursors. This now makes up the product GLYLO.
Preliminary testing of GLYLO in animal models has shown improvements in insulin sensitivity and lifespan extension. But interestingly, it also caused the animals to lose weight. Why? Check out the interview to learn more!
This Week's Research Highlights
💊 Supplementation with carnosine reduces formation of AGEs in the body and improves markers of glycemic control.
Fifty-four patients with type 2 diabetes were randomly assigned to take either l-carnosine (500 mg twice per day) or placebo. After 12 weeks, the group taking carnosine had significantly lower levels of carboxymethyl lysine and serum pentosidine, both of which are biomarkers for formation and accumulation of advanced glycation end products, as well as lower levels of tumor necrosis factor–α, an inflammatory cytokine which promotes insulin resistance and is associated with type 2 diabetes. This was accompanied by improvements in both body composition and glycemic markers in these patients. The carnosine group experienced a significant reduction in fat mass (−1.5%) and increase in fat-free mass (+1.7%), along with lower fasting blood sugar (−13.1 mg/dL), HbA1c (−0.6%), and serum triglycerides (−29.8 mg/dL).
Forty-six patients with type 2 diabetes were randomly assigned to take either taurine (3 g per day) or placebo. After 8 weeks, the taurine group showed significant reductions in serum pentosidine as well as methylglyoxal (the latter of which is the AGE precursor that GLYLO targets). Compared to placebo, they also had lower fasting blood sugar (−10.97 mg/dL), lower hbA1c (−0.21%), lower insulin, lower insulin resistance, and lower LDL (−10.37 mg/dL). And as we’ve discussed in prior newsletters, taurine has other interesting benefits associated with it, perhaps most notably for blood pressure regulation.
🥦 Eating a diet designed to be low in AGEs decreases urinary AGEs and improves insulin sensitivity. Prior lab research
has shown that how you prepare food can make a big difference in AGE formation. For instance, it was shown that exposure to dry heat can promote AGE formation by up to 100-fold above the uncooked state. Cooking with mild moist heat, like poaching or steaming, can drop AGE formation in proteins like chicken and eggs by as much as 75%. To explore the impact of these sorts of modifications, researchers recruited 74 women and randomly assigned them to follow a high-AGE or low-AGE diet for four weeks. Importantly, these diets were cleverly designed to be very similar in composition and nutrients, but primarily differed in cooking methods. For instance, for dinner the high-AGE group would consume breaded cod filet while the low-AGE group would eat steamed cod, and for breakfast the high-AGE group would eat a crunchy cold cereal while the low-AGE group ate oatmeal.
Sure enough, at the end of the study, levels of urinary advanced glycation end products (carboxymethyl lysine and methylglyoxal) were substantially lower in the low-AGE group, but remained unchanged in the high-AGE group. This in turn was linked to a reduction in insulin resistance in the low-AGE group.
Random Trivia & Weird News
The active ingredient in sunless tanners is the compound dihydroxyacetone (DHA). DHA reacts with amino groups in the proteins of the top layer of the skin (stratum corneum), forming brown compounds called melanoidins.
It does so through the same chemical process that leads to the formation of AGEs in food exposed to high heat, as described above.
Podcasts We Loved This Week
- Danny Lennon & Alan Flanagan: Do artificial sweeteners increase cancer risk? Via Sigma Nutrition Radio.
- Matt Walker: Understanding sleep and how to improve it. Via The Drive.
Products We Are Enjoying
When Pankaj performed his screening process, five compounds emerged: Alpha lipoic acid, nicotinamide, piperine, pyridoxamine, and thiamine. When tested in animal models, the formulation reduced glycolytic byproducts, as expected, but it also caused the rodents to eat less.
Does this mean that glycation contributes to obesity?
We do know that modern diets tend to be higher in AGEs due to preparation methods and processing, so it’s not a crazy idea. If you struggle with your appetite, or just want to increase lifespan and healthspan by blocking AGEs, I think it’s worth a shot.
humanOS Catalog Feature of the Week
This week, we’d like to highlight our how-to guide for chrononutrition. We often fixate on what we are eating, when we are discussing diet and lifestyle, but we are gradually appreciating that when we eat also has a significant impact on our health and our daily performance.
This guide will help show you how to optimize your food timing, in alignment with the latest scientific research, to maintain robust circadian alignment and to ensure you are performing at your very best.
(PS: If you’re looking for a deeper dive into the subject of nutrient timing and other aspects of circadian physiology, please refer to our Circadian OS Program.)
Thanks for reading, enjoy the weekend, and we'll see y'all next week!