Nutrient Focus – Anthocyanins

What’s in your food? Most people are aware of the macronutrient classes protein, fat, and carbs, as well as the essential micronutrients – vitamins and minerals. Additionally, water and fiber don’t fit into either category. But there’s long been much excitement over phytochemicals, the organic compounds produced by plants that are not considered vitamins because they are nonessential. These include polyphenols like resveratrol, which is toxic to cancer cells and augments metabolism and extends lifespan in mice. Frustratingly, observations of resveratrol’s beneficial effects repeatedly fail to replicate in humans. This conundrum is referred to as the ‘resveratrol paradox’, and reflects our as-yet incomplete understanding of how we could activate resveratrol’s mechanism in vivo with other chemical agents. But I’m not talking about resveratrol today; instead I’ll discuss one of the most abundant classes of phytochemicals in fruits and vegetables, namely, anthocyanins.

Anthocyanins are a subclass of flavonoids, which are colorful phytochemicals found in plants and fungi. Flavonoids serve a number of roles including attracting pollinator animals, absorbing UV radiation, and affecting signal transduction in plant cells. This makes them secondary metabolites, auxiliary molecules that make the organism run more smoothly; however, their production can be shut down if the plant doesn’t need them. For instance, a plant growing in low sunlight won’t need to express as much ‘sunscreen’ in the form of UV-absorptive flavonoids. As another example, a plant that is unchallenged by antagonists like pests or fungi won’t need to engage in chemical warfare to keep from getting eaten. Importantly, flavonoid expression is controlled by the genes encoding flavonoid-synthesizing enzymes, so flavonoid levels will vary among cultivars by how they’re bred, selected, and in some cases, engineered.

So what’s unique about anthocyanins among the larger class of flavonoids? For one, their polyphenolic structures produce particularly intense colorations. Along with carotenoids such as β-carotene, anthocyanins are the most used vegetable pigments by the food industry; however, whereas carotenoids are fat-soluble, anthocyanins are water-soluble and less stable. They abound in most pigmented fruits and berries, but also in vegetables like beets and red cabbage. Anthocyanins are also potent antioxidants, which is why they are good “sunscreen” for plants. Their polyphenolic structures can capture and stabilize free radicals generated by UV radiation long enough to neutralize them and prevent their propagation amongst more vulnerable biomolecules in the plant.

Thus far I’ve told you why plants make anthocyanins and what they do for their hosts, but what we really care about is what they do for humans as part of our diets. Purified anthocyanin extracts have, like resveratrol, shown antiproliferative effects on human cancer cell lines and in animal models. But when it comes to benefits in humans we need to be careful: studies of supplementing diets with berry extracts and/or juice seem promising but often caveats of small sample size and lack of proper controls are revealed in the conclusions. Pop-sci outlets leave those caveats out and run with the most exciting parts, irresponsibly perpetuating data out-of-context. Too often science is stripped of its experimental context and presented as certainty by those without the authority to do so.

This gets at a general idea that I’ve come around to in my musings on diet: despite what we all want to believe, there really is no singularly awesome food or nutrient that will make a dramatic change to your health. There isn’t anything even close to one. You won’t see a significant improvement by solely adding wild blueberry juice to your breakfast. It’s more holistic than that, and it’s not antiscientific of me to say that! Science at this point simply lacks the resolution to tell exactly what components of foods are most nutritious or antiproliferative in humans. Furthermore, food is not a batch-controlled pharmaceutical and there can be much variation based on sourcing, storage, etc.

Anthocyanins are a great example of this. If you’ve made it this far, let’s get more granular: anthocyanins are actually composed of a positively-charged core flavylium scaffold called an anthocyanidin (shown in blue) and attached sugars, or glycosides. There are over 500 different anthocyanin molecules reported, but they are built upon only 23 distinct anthocyanidin scaffolds. An example of their diversity can be seen in the two structures shown: both violdelphin and tulipanin are composed of the same core anthocyanidin, but differ in the number and type of glycosides, as well as where those linkages occur. Unique anthocyanins must be extracted and purified prior to characterization, but any given foodstuff is going to contain a diverse repertoire. Each has a different antioxidant potential based on how and which sugars are assembled on which scaffold: generally, the more sugars the lower antioxidant capability.

tulipanin (left) from alstroemeria, petunia, blackcurrant, tulip, and black eggplant, among others. violdelphin (right) from the Aconitum carmichaelii or Fu Zi flower. Both are built upon a delphinidin anthocyanidin core, and have an attached rhamnose sugar at C3, but violdelphin has an additional glycoside at C7.

It gets more complicated still. Anthocyanins’ phenolic oxygens can interact with metals, amino acids, nucleic acids, polysaccharides, or even other anthocyanins to form co-pigments. These complex interactions further augment the stability and antioxidant potential of anthocyanins. Their nutrient and antioxidant value will also vary by sample, by species, by age of the sample, by storage conditions, by aforementioned genetics, and so many other factors. And here’s the kicker: the better the antioxidant a given anthocyanin is, the less stable it is, because it will react more readily with a free radical before it gets into your mouth.

It’s important to consider these sources of variability and unknowns. Here’s one crucial thing we know: anthocyanins display poor absorption and pharmacokinetic properties. Rather than being absorbed into the bloodstream and circulating through the tissues where they could exert some beneficial effect, most go straight into the urine, intact, without any metabolic processing. Anthocyanins never reach the required concentration in vivo to exhibit anti-carcinogenic effects demonstrated in vitro. I wouldn’t be surprised if consumption of anthocyanin-rich foods in the context of a high-fiber meal boosted their circulation, but it’s unlikely to reach that of the high doses employed in experiments.

I don’t want to discourage you from trying to get your fill of anthocyanins; quite the opposite actually, but that’s because anthocyanin-rich fruits and veggies also tend to be rich in fiber and macronutrients. I’m a big believer in a whole foods-based diet that eschews most processed food. If you’re trying to eat more berries, more power to you. However, I think most of us could make simpler changes than trying to make the perfect smoothie every morning for the rest of our lives, like eating out less and cooking more. The next time you hear a health food buzzword like superfood or antioxidant or cancer-fighting, consider what’s behind the façade of the word itself. There really aren’t any dietary shortcuts or life hacks. Anyone trying to tell you differently probably wants to sell you something.

All the great anthocyanin specifics came from these reviews:

Wang, L.-S. & Stoner, G. D. Anthocyanins and their role in cancer prevention. Cancer Letters 269, 281–290 (2008).

Castañeda-Ovando, A., Pacheco-Hernández, M. de L., Páez-Hernández, M. E., Rodríguez, J. A. & Galán-Vidal, C. A. Chemical studies of anthocyanins: A review. Food Chemistry 113, 859–871 (2009).

Kamiloglu, S., Capanoglu, E., Grootaert, C. & Van Camp, J. Anthocyanin Absorption and Metabolism by Human Intestinal Caco-2 Cells—A Review. IJMS 16, 21555–21574 (2015).