Flavonoids, Healthy Living, and Magic Potion Studies

Longevity studies often make the news, because people want to live longer, healthier lives.

Especially popular are "magic potion" studies that focus on the benefits of a single food or lifestyle change.

Last week, for example, a new report linking coffee consumption to healthier aging got a lot of attention.

There's nothing inherently wrong with magic potion studies, so long as we don't overestimate the "magic" or the uniqueness of the "potion".

Drinking coffee does seem to promote longevity. More than 15 years of research attests to that. But the effects are small, and it's unclear whether they stem from the caffeine, other antioxidants, or something else in your daily brew.

In other words, whatever "magic" coffee contains is limited in potency and may be available from other sources too.

In this newsletter I'll be discussing an alternative to the magic potion approach. Specifically, a new study revealing links between flavonoid intake and healthy aging.

What makes studies like this different is attention to diversity. The results point to some "magic" in eating the right mix of flavonoids rather than just one type.

Flavonoids

Flavonoids are chemical compounds found in plants and plant products such as tea and wine.

Plants rely on flavonoids for pigmentation (rich blues, reds, and yellows that attract pollinators) as well as for protection against stress (excessive heat, drought, etc) and other functions.

Flavonoids are good for us too, as I'll explain shortly. There are more than 5,000 of these compounds, and I'm going to discuss each one.

Just kidding. There are five major types. The table below, created from the most recent USDA data, provides examples of each. (Entries are for raw foods unless otherwise noted.)

The final column reflects a typical American diet. You can also get flavonoids from foods not listed here, including kale, soy products, red wine, dark chocolate, coffee, et cetera.

Flavonoids and health

Flavonoid intake has been linked to better cardiovascular health, improved cognition, longer life, and much more.

As you might expect, there's a lot of hokum and misinformation floating around too.

For instance, here's a screenshot from the Cleveland Clinic website, a respected source of health information (and often a top-ten Google hit):

Sorry, no.

The hyperlink leads to a 2013 review – not a study – suggesting that flavonoids might be anti-carcinogenic.

I want to dig deeper here, because I hate cancer-related misinformation. Plus, the Cleveland Clinic's mistake illustrates a key problem with magic potion claims.

At most, some studies hint that flavonoids could help prevent cancer.

Certain flavonoids kill cancer cells in petri dish-type studies. That's clear enough. But data obtained from living, breathing, food-consuming human beings is mixed – some studies show protective effects, others don't.

Plus, the studies in question don't measure flavonoid intake directly. Rather, they look at proxies like fruits and vegetables, and perhaps also tea, red wine, and/or dark chocolate.

Eating more fresh fruits and vegetables indeed lowers the risk of cancer. But the effects are small, and it's not clear whether we should thank the flavonoids, other constituents such as vitamins and minerals, or the fact that the more plants you eat, the less room you have in your belly for carcinogenic stuff like processed red meats.

I'm not suggesting anything original here. Nutrition scientists are quite aware of these interpretive issues.

Bottom line: There's no credible, direct evidence that eating more flavonoids per se lowers the risk of cancer.

Much the same can be said for other health benefits, except that in recent years, researchers have begun to focus on specific flavonoid compounds.

For instance, in a 2022 study, more than 20,000 older adults spent 5 years taking daily flavanol supplements extracted from cocoa. ("Flavanols" are the same as flavan-3-ols but different from flavonols – confused yet?) Compared to a placebo group, deaths from cardiovascular disease were eventually 27% lower among those taking the flavanol. Good news for cocoa and chocolate lovers!

Studies like this suggest that increasing flavonoid consumption might be healthful, but the data are preliminary.

In sum, lots of magic potion studies explore the health benefits of flavonoids, but it's not clear yet whether greater flavonoid intake per se is beneficial.

Now for a study that incorporates a different approach.

The new study

This study was published on June 2 in Nature Food, an esteemed nutrition journal.

Lead author Benjamin Parmenter (Queen's University Belfast; Edith Cowan University) and an international team analyzed data from the UK Biobank, a massive, ongoing longitudinal study.

Parmenter and colleagues focused on 124,805 adults who enrolled in the study between 2006 and 2010. These individuals ranged in age from 40 to 60 at the time of enrollment and were tracked for roughly a decade.

(You might ask: Why not track people longer, like through 2025? The UK Biobank is so large and complicated that new data only gradually becomes available for analysis.)

Parmenter and colleagues' main interest was in the relationship between flavonoid intake and health outcomes.

On five occasions between 2009 and 2012, each participant recorded exactly what they ate during the previous 24 hours. The researchers then estimated flavonoid intake based on types and quantities of food eaten.

(This is a crude approach to measurement, but to be honest I'm tired of picking on observational studies for this kind of thing. There's just no way to record exactly what people eat each day for a period of years. You just have to hope that a signal emerges from the noise, and that studies differing in methodology yield similar findings.)

Parmenter and colleagues looked at six health outcomes not exhibited by participants when they began the study:

• cardiovascular disease

• cancer

• neurodegenerative disease

• respiratory disease

• type 2 diabetes

• all-cause mortality (i.e., death from any cause)

Main findings

1. Quantity matters.

The more flavonoids people ate, the less prone they were to each of the six health outcomes.

This is good news. The effects for each outcome (expressed as hazard ratio differences) were small but significant.

You might be wondering: What exactly were people eating more of? As the researchers note:

Tea (black and green) was the main source of total flavonoid intake (67%), followed by apples (5.8%), red wine (4.7%), grapes (1.9%), berries (1.9%), dark chocolate (1.2%), oranges and satsumas (1.1%) and orange juice (1.1%)..."

Notice the huge difference between tea and the rest. If Parmenter and colleagues had been planning a magic potion-type study, they could've emphasized the point and made their study about tea. But their main interest was in diversity.

2. Diversity matters.

The more diversity in the types of flavonoids people ate, the less prone they were to five of the six outcomes (all but neurodegenerative disease).

Diversity is a bit complicated, mathematically speaking, but here's the key point: Quantity and diversity are independent of each other.

For instance, two people might eat the same amount of flavonoids but differ in the diversity of the types they consume.

Or, two people might eat an equally diversified range of flavonoids but differ in how much of each type they consume.

Diversity matters, the researchers speculate, because each flavonoid differs in the way it supports health.

Can we trust the findings?

Yes, but not exactly the way they're presented.

If the researchers are right, then as flavonoid intake increases, health problems decrease. Likewise for the diversity of flavonoid intake.

Is that what the data shows?

Take a look at the excerpt below from one of the researchers' figures.

Each dot represents a quintile. The dot on the far left is for the 20% of participants with the least diverse flavonoid intake. The dot on the far right is for the 20% with the greatest diversity. The y-axis indicates risk of cancer. The farther a dot is below the dotted line, the greater the reduction in risk. (The dot on the far left – the lowest quintile – serves as a reference point.)

If greater diversity in flavonoid intake offers greater protection against cancer, you'd expect those dots to trend downward from left to right.

You can start to see that trend until you get to the fourth dot, which rises above the two behind it. Though this group is eating a more diverse range of flavonoids, they're slightly more likely to develop cancer.

In addition, the fifth dot is slightly higher than the third one, which is to say that folks with the most diversity in flavonoid intake are slightly more likely to develop cancer than folks in the middle.

You might think we're seeing minor anomalies in the data. This does happen. But every one of the researchers' figures shows some pattern like this.

Still, there's good news here. Notice that all of the dots are lower than the first one. This can be seen in nearly every one of the researchers' figures.

In other words, the 20% of people whose diets are lowest in flavonoid quantity and diversity have a higher risk of developing cancer and other health problems than the other 80%. The differences are small but significant.

My takeaway from the study is not that increasing the quantity or diversity of flavonoid intake is generally helpful. Rather, you just need to be sure your intake exceeds some minimal, yet-to-be determined values.

Practical advice

1. Reflect on your flavonoid intake.

I'm not suggesting that you start doing calculations. The flavonoid content of most foods changes in response to storage time, environmental conditions, and method of preparation. In some cases, it matters what foods are combined (e.g., an enzyme in bananas reduces the bioavailability of flavonoids in berries). We're not even sure what healthy minimums would look like in the first place.

My suggestion is this: If you rarely eat fruits and vegetables, eat more, or at least check whether your current diet covers the five major flavonoid types.

Some nutritional guides recommend more concretely that you "eat a rainbow".

This isn't bad advice, as you'd get plenty of flavonoids such as anthocyanins, as well as other key nutrients. You'd still need to watch your intake of colorless nutrients, like protein, and you wouldn't want to necessarily overlook flavonoid-rich but relatively pale foods like bananas, cauliflower, and lettuce.

Experts also routinely encourage us to eat a variety of foods.

A varied diet will probably be diverse with respect to flavonoid content, but not necessarily so.

For instance, a carnivore diet, or even a keto diet, might be varied in the sense of including a wide variety of animal products, along with some plant foods, but if the plants you eat are primarily nuts and an occasional veggie or fruit, your diet won't be very flavonoid diverse.

2. Don't stress about flavonoid hacks.

Flavonoids may be good for you, but we don't know what quantities are optimal. At best the benefits of relatively high quantities and/or diversity seem small. Changing other aspects of your diet and lifestyle might do you more good than worrying about which vegetable to serve with dinner.

3. Don't get myopic.

USDA data shows that among Americans at least, beer is a major source of flavan-3-ols. Other studies have linked flavan-3-ol consumption to cardiovascular health. That doesn't mean you should drink lots of beer. At some point, the more you drink, the more the cardiovascular damage would outweigh any benefits from the flavan-3-ols.

Another example is that even though processed juices such as reconstituted orange juice are relatively high in flavonoids, fresh juice may be healthier (though some data suggests that carotenoids are more bioavailable in frozen juice). In any case, as Mick Skolnick explains this week in his Healthy Living is Good Medicine blog, whole oranges are even better than the juice.

The point of these examples is that we should consider everything in the foods we eat rather than just focusing narrowly on single constituents like flavonoids.

Final thoughts

The popularity of magic potion studies taps into something fundamental about the way our minds work.

More than 3,000 years ago, in The Epic of Gilgamesh, the hero learns of a plant growing at the bottom of the ocean that supposedly confers eternal life.

Notice that Gilgamesh isn't told about, say, two plants and a sacred ritual. Just one plant supposedly holds the magic.

We have a tendency to view complex outcomes as having simple or even single causes. Many scholars, including Daniel Kahneman in his 2011 book Thinking Fast and Slow, have remarked on the advantages and disadvantages of this natural tendency.

I believe that single-cause thinking accounts for the appeal of magic potion studies. There's nothing inherently wrong with claiming that coffee, or cantaloupe, or kale, is uniquely healthful. Some of the evidence is credible, some not so much. But focusing on any one food could only capture part of a complex story. Nutrition is one more realm in which there's strength in diversity and we find many contributors to good health.

Thanks for reading!