The Tea Paradox

Ironically, the boosting of antioxidant and DNA-repair defense forces seems to be a consequence of the mild pro-oxidant properties of green tea, a phenomenon that runs similarly with physical training. It is called the “exercise-induced oxidative stress paradox.” Ultramarathon runners can produce so many free radicals during a race that they can damage the DNA of a considerable percentage of their own cells. But why does an apparently healthy activity (exercise) have adverse effects? Because exercise in and of itself is not necessarily healthy; it’s the recovery time afterward. For example, exercise training increases antioxidant defense mechanisms by increasing the activity of antioxidant enzymes. Athletes may therefore strain their DNA during a race, but a week later they do not simply fall back to the same level of DNA damage. Daily, routine DNA damage is even lower, presumably because the preceding exertion got their antioxidant defenses going.

Seen this way, the mild oxidative stress from green tea or exercise is useful, similar to a vaccination. By challenging the body, we provoke a response that benefits us in the long run. The view that low amounts of a damaging exposure ramp up protective mechanisms—“what doesn’t kill us makes us strong”—is called hormesis.

Taking antioxidant pills, for example vitamin C and vitamin E supplements, can block this boost in antioxidant enzyme activity from physical activity and thereby block some of the resulting health benefits, but consuming antioxidant-rich foods may combine both advantages. Vitamin C supplements seem to impair physical performance, whereas fruits and vegetables can increase it without undermining the protective adaptive response. In fact, fruits and vegetables even enhance the benefits of exercise. Both black currants and lemon verbena, an herbal tea that is rich in antioxidants, have been shown to protect against oxidative stress during exercise while simultaneously producing some beneficial adaptations to movement.

In view of the hormetic benefits of a certain amount of mild oxidative stress, for example green tea and physical activity, the overly simplistic “antioxidants: good, free radicals: bad” must be revised. Nowhere is this clearer than with broccoli.

Kale flips the switch

The antioxidants from food, for which we use plants, are only our second line of defense against free radicals. On the front line are our own antioxidant enzymes. The human body naturally produces 100 trillion (100 000 000 000 000 000 000 000) free radicals per hour. For this reason, we make enzymes such as catalase, the fastest-reacting enzyme in our body, which can literally neutralize millions of hydrogen peroxide molecules every second and break them down into water and oxygen. (You know the fizzing when you pour hydrogen peroxide on a wound? That comes from the oxygen bubbles that the enzyme catalase forms.) Is there a way to activate this front line in antioxidant defense?

In the 1980s, scientists discovered a particular gene sequence in the promoter regions of dozens and then hundreds of “cytoprotective” (cell-protecting) genes. They found that it promoted genes that code for antioxidant enzymes that, like catalase, directly smother free radicals, enzymes that produce antioxidants like glutathione, and even genes for DNA repair enzymes and detoxifying enzymes in the liver. Whatever does the binding to these so-called antioxidant response elements could activate our global antioxidant defense system all at once.

In the 1990s, this trigger was discovered—Nrf2, a protein that floats around in the cell’s cytoplasm and is normally bound to a suppressor protein. But if this suppressor protein is oxidized, it releases Nrf2, which then penetrates into the cell nucleus, binds to the antioxidant response elements, and activates the heavy artillery of antioxidant protection mechanisms. The whole process can be completed after 15 minutes. Nrf2 is regarded as the “master regulator of the environmental stress response.” It is universally expressed in all cells, where it is just waiting to be released, to press the panic button, and to mobilize cellular defense mechanisms.

Nrf2 is also called the “keeper of life expectancy and guardian of a species’ longevity.” Cranking up Nrf2 signaling substantially increases life expectancy in C. elegans and fruit flies and correlates, in ten different rodent species, with maximum life expectancy. For example, the Nrf2 gene is overexpressed sixfold in long-lived naked mole-rats compared with mice and has a lower expression of the suppressor protein. This could explain not only why naked mole-rats live eight times longer, but also why it takes up to 100 times more concentrated toxins such as heavy metals or chemotherapy drugs than in mice to kill the same percentage of skin cells. Naked mole-rats are small, hairless detox machines.

Unfortunately, the Nrf2 level and its signaling function tend to decline with age. For example, 30 minutes of cycling can give them a push, but the strongest natural trigger of Nrf2 on the planet is probably sulforaphane, the compound that forms when we bite into cruciferous vegetables such as broccoli, kale, collard greens, white cabbage, and cauliflower. Like the active components in green tea and turmeric, sulforaphane frees Nrf2 by oxidizing the protein that suppresses it, which in the end rejuvenates old mice. Fed sulforaphane, older mice had more grip strength than younger ones, and on the treadmill they did just as well. Activating Nrf2 led to less DNA damage and muscle loss and improved heart function and life span.

And in us? Sulforaphane can also restore Nrf2 activity in our aging tissue, which would explain why sulforaphane can delay the senescence of human stem cells. Just one broccoli stalk daily substantially reduces DNA damage from cigarette smoke, and two cups of Brussels sprouts per day can minimize the DNA damage triggered by a certain carcinogen in cooked meat (a heterocyclic amine). About one third of a cup of broccoli sprouts can help our body neutralize benzene from polluted air. One study found that sulforaphane can dampen the inflammatory response triggered by diesel exhaust—for this, the subjects were sprayed in the nose with a concentration that corresponded to hours of exposure on a freeway in Los Angeles during rush hour.

Cruciferous vegetables stimulate our detoxification pathways in such a way that people who eat a lot of broccoli may have to drink more coffee to produce the same energy boost, since the pathway that processes substances and also takes up caffeine can be so strongly stimulated. The protection that vegetables in the cabbage family grant us even shows up externally. If you rub yourself with a broccoli extract before going out into the sun, that yields 35 percent less reddening from sunburn, because UV radiation’s tissue damage is reduced by Nrf2 activation.

The discovery that sulforaphane can switch on Nrf2 probably ushered in a “new paradigm in nutrition science.” No wonder that eating cruciferous vegetables is seen in connection with a lower risk of cardiovascular disease, cancer, and death from all other causes. Even those who on average eat only a single floret of broccoli a day have lower mortality rates than others who rarely or never reach for broccoli. Yet broccoli’s life-extending effect might even go beyond that of sulforaphane. Animals whose feed was mixed with one percent broccoli lived longer, but others that were given sulforaphane in the same amount as in broccoli, but without the broccoli, did not. Salad with sulforaphane beats sulforaphane supplements.