Newsletter #291

Last week, we discussed how to combat cellular senescence through physical activity. But what exactly stimulates cells to enter that state in the first place?

Well, senescence often occurs as a sort of defensive response to DNA damage. We accumulate DNA damage over time, due to both endogenous processes and environmental stressors. Perhaps the best-known outcome of this is cancer, but DNA damage plays a role in multiple known hallmarks of aging, and may contribute to virtually every age-related disease.

Mechanisms through which DNA damage promotes aging. From: 10.7554/eLife.62852

Notably, there is some reason to believe that nutrition plays a role in DNA integrity. In his Triage Theory, Bruce Ames proposes that suboptimal nutrient intake could contribute to cancer due to a sort of rationing response, selected for by evolution.

Here’s the basic idea: Most people get enough vitamins and minerals in their diet to prevent overt deficiency symptoms. But plenty of folks still consume diets that are not especially nutrient-rich. So what happens if you’re just getting enough essential nutrients and antioxidants to keep the lights on, so to speak? In that case, your body is effectively stuck on a tight budget. Thus, the nutrients that you are consuming get preferentially directed to proteins and enzymes that are essential for survival, and the body has to skimp on proteins that help us repair and rebuild our bodies and fight diseases of aging.

This becomes especially relevant with respect to cancer. You see, vitamins and minerals function as cofactors for DNA repair enzymes, as well as cellular defense mechanisms that combat potential carcinogens from the environment. It has been suggested that this may be why low consumption of nutrient-dense fruits and vegetables has been linked to double the risk of most cancers. And as you’ll see from the trials described below, non-essential bioactive compounds, like phytochemicals, may also help stimulate these protective pathways.

A trial in smokers found that eating broccoli for ten days led to a reduction in markers of oxidative DNA damage. Since smoking leads to greater exposure to genotoxic compounds and free radicals, it makes sense that they would strongly benefit from the antioxidant properties of cruciferous vegetables.

To examine whether the potential anticarcinogenic effects of this class of vegetables could also extend to non-smokers, an Italian research team recruited 20 healthy young students (10 smokers and 10 nonsmokers) from the University of Milan, and put them through two 10-day diet interventions, which were separated by a 20-day washout period.

During one period, they visited the lab every day and consumed a 200g portion of steamed broccoli at lunch. Then, through the control period, they stuck to their regular diet but were forbidden from eating cruciferous vegetables. Blood samples were collected before and after the experimental and the control periods, which the researchers analyzed for signs of DNA damage and other biomarkers.

When they examined levels of exogenous DNA damage (meaning, in response to environmental stressors) in the white blood cells of these men, they found that DNA strand breaks decreased by more than 22%. And when they broke down the results by smokers and non-smokers, there was no significant difference in this effect — both benefitted similarly. Furthermore, the level of oxidative DNA damage returned to baseline after the men stopped consuming broccoli, indicating that the vegetable was indeed responsible for the observed effect.

Why does broccoli do this? Well, one way that our bodies combat cancer is through phase 2 detoxification. Basically, enzymes tag potentially cancerous toxins with specific molecules to neutralize them and make them easier to safely excrete before they can cause trouble. Metabolites generated from cruciferous vegetables, like sulforaphane, have been shown to boost production of these antioxidant enzymes. This is why having people consume broccoli sprouts has been shown to ramp up excretion of carcinogenic pollutants, and potentially why crucifers have been linked to lower likelihood of cancer.

In an earlier study, researchers found that feeding people carotenoid-rich foods (tomatoes, carrots, spinach) reduced the number of DNA strand breaks in white blood cells. However, these foods contain a zillion different chemicals, making it hard to say for sure if the observed protective effects could be attributed to carotenoids, or even which carotenoids might be driving the benefits. To narrow it down, Tufts researchers recruited 37 healthy women, aged 50-70, and randomly assigned them to one of five different supplement groups:

All subjects took their supplements daily for 56 days, and blood samples were taken before and after to measure carotenoid concentrations as well as DNA damage.

Much as you would anticipate, plasma levels of carotenoids skyrocketed after the supplement regimen, going up by 228%-514% of baseline levels. When they examined exogenous DNA damage (like what was measured in the broccoli study), they didn’t see a significant effect.

However, free radicals don't just emanate from the environment, they are also continuously produced as a part of normal cellular functioning. The carotenoids did lead to a substantial reduction in endogenous DNA damage, measured by double-stranded breaks, in all supplement arms:

Finally, it's worth noting that although this is a supplement trial, as opposed to a whole food trial, the doses of carotenoids being administered to these subjects could realistically be obtained from foods. For instance, 4 mg of lutein can be found in just a quarter-cup of cooked spinach, and 4 mg of lycopene is the amount found in one medium-sized tomato.

🦎 The first GLP-1 analogue on the market was isolated from the saliva of Gila monsters.

Gila monsters are venomous lizards found in the southwestern US, which supposedly have exquisitely painful bites. Importantly, they have profoundly low resting metabolic rates – so much so that they can get away with only eating a few meals per year.

To gain some insight into the creature’s venom and why it elicits so much agony, scientists began analyzing their saliva. They discovered a hormone in the lizard’s saliva called exendin-4, which happens to be very similar to human GLP-1 but with a longer half life. This hormone seems to help the reptiles digest their meals extra slowly, enabling them to eat less frequently. Synthetic preparations were developed to modulate blood sugar in patients with type 2 diabetes, and they have since evolved and eventually been repurposed into the remarkably effective anti-obesity drugs we see today.

Image from LA Zoo

Sulforaphane is a potent inducer of Phase II enzymes, and is thought to drive much of the health benefits described in the study above which tested broccoli.

Now, you would have to eat an awful lot of broccoli to even get close to the dose found in this supplement, so for those of you who can’t handle tons of crucifers (especially raw), or just people who want to take full advantage of the detoxifying power of sulforaphane, this could be your best bet. You can also try growing broccoli sprouts as well!

This week, we’d like to highlight our course on smoothies and phytochemicals.

The course takes a deep dive into phytochemicals in plants, where they are found, their powerful health effects, and how intelligently-devised smoothies can help optimize our intake of these compounds.

For more practical information on using smoothies to enhance nutrition, please refer to our How-to Guide for smoothies.

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