Newsletter #214

is a natural activator of a class of enzymes known as sirtuins, and most notably of SIRT1. SIRT1 plays an important role in maintaining cellular homeostasis, potentially leading to better health and longevity, and it is thought that activation of SIRT1 is one of the reasons why exercise is good for us. To explore how antioxidant vitamins might affect this process, researchers recruited 32 middle-distance runners and split them into two groups. One group was assigned to take 240 mg of vitamin C and 15 mg of vitamin E every time that they trained. The other group didn’t take any antioxidants and just worked out like normal. The researchers also enrolled 14 sedentary volunteers, who were around the same age as the runners, as a control group.

At the end of the study period, the researchers found that the runners who didn’t supplement had higher levels of SIRT1 mRNA expression and activity than either of the other two groups. The runners who took the antioxidant vitamins, in contrast, had similar levels of SIRT1 mRNA expression and activity as the control group - indicating that the beneficial effect of exercise on SIRT1 was lost. This finding echoes previous studies, showing that supplementation with antioxidants can impair adaptations to training, as well as prevent exercise from improving insulin sensitivity (check out this podcast to learn more). Key takeaway here is that we need small doses of free radicals to trigger many of the health benefits associated with exercise, and obliterating them could actually be counterproductive in the long term.

Mitochondrial dysfunction, as you may already know, is one of the hallmarks of aging. Unfortunately, as we get older, we tend to accumulate broken mitochondria that are ineffective at generating the energy we need, but are also resistant to natural recycling processes (known as mitochondrial autophagy, or mitophagy). Consequently, there has been enormous interest in identifying compounds that can help ramp up mitophagy and therefore improve cellular health. One such bioactive currently being investigated is urolithin A, a metabolite derived from polyphenols found in pomegranates (refer to this podcast to learn a little more about how it works). To explore how urolithin A might affect age-related muscle decline - a problem for which there are basically no effective interventions right now - researchers recruited 88 middle-aged adults and split them into three groups. One group received 1000 mg of urolith A, another group received 500 mg of urolithin A, and finally the third group was treated with placebo.

After four months, as we would expect, urolithin A increased muscle mitochondrial content and upregulated markers indicative of mitophagy. The urolithin groups also showed lower levels of inflammation, measured by CRP and various inflammatory cytokines. But the functional improvements are the really cool part: both urolithin groups experienced significant increases in leg muscle strength. For instance, average peak torque in their hamstring went up 9.8-12%, compared with placebo. The higher dose urolithin group also showed increased peak VO2 (+10%), which translated into improvements in both walking and cycling distance.

Allergies are highly prevalent, but the underlying causes are still yet to be fully elucidated. Years ago, it was observed that growing up on a farm was associated with lower risk of asthma and allergy - known as the “protective farm effect” - and it has been hypothesized that components of the whey fraction of raw cow’s milk may be a major contributing factor of this association. Whey protein β-lactoglobulin is aerosolized into the air around farms, and is thought to modulate the immune system in ways that protect against allergic sensitization. Additionally, micronutrient deficiencies have been shown to be linked to allergy and immune hyperreactivity, especially functional anemia. To try to address these possible risk factors, researchers recruited 58 women with known allergies and randomly assigned them into two arms: one was given placebo, and the other was given special lozenges based on β-lactoglobulin, which acted as a carrier for various nutrients including iron, polyphenols, retinoic acid, and zinc.

Study leader Franziska Roth Walter explained, "Thanks to this carrier, absorption takes place via the lymph instead of blood vessels—in other words, exactly where immune cells are present in abundance ensuring micronutrient uptake in a targeted manner." Sure enough, after six months of intake, the experimental group showed an improvement in iron status of their immune cells, and a 31-45% improvement in their symptoms during birch and grass pollen seasons. Furthermore, their nasal symptom score after a nasal challenge in the lab improved by 42%.

This, of course, means that a lot of their vital signs sound crazy by our standards. For instance, their heart rates can reach as high as 1,260 beats per minute, and their breathing rate is around 250 breaths per minute at rest. While flying, their oxygen consumption per gram of muscle tissues is 10 times higher than that seen for elite human athletes.

Perhaps unsurprisingly, they also exhibit insanely high fasting and postprandial blood sugar to power those tiny beating wings - fasted glucose is around 300 mg/dl, and it increases to 740 mg/dl after feeding. Researchers noted, “How hummingbirds tolerate blood glucose levels that cause serious neurological and microvascular pathologies in diabetic humans and animals remains unknown.” Gotta think this merits further investigation.

This week, we’d like to highlight our How-to Guide for Smoothies. We know that consuming a nutrient-rich diet made up of fresh whole foods is key for performing at your very best, both physically and mentally, and maintaining a healthy weight. One efficient and convenient way to ensure that you’re making that happen on a daily basis is through smoothies. Incidentally, smoothies can also be a very convenient vehicle for powder supplements - I like to add my creatine and other stuff to the blender to make them easier to take.

But obviously not all smoothies are necessarily a smart choice from a nutritional standpoint, which is why we developed this science-based guide to constructing healthy smoothies. For a slightly deeper dive, please refer to our course on smoothies and phytochemicals.

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

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