Part 3: Polyphenol Practical Applications and Adverse Effects
Practical Applications
This is all nice to know, but what practical applications can we take away from this knowledge in order to improve our lives? The most obvious one is increasing your intake of polyphenol-rich foods. Polyphenols are found in many naturally derived foods such as fruits and vegetables. In contrast, processed foods contain much less if, if not none at all. Replacing processed foods with natural foods has been consistently shown to lead to improved health outcomes. Reasons for this include a high proportion of vitamins, minerals, fibre, and bioactive compounds such as polyphenols.
Aside from this, though, one takeaway that might be less obvious is the necessity to incorporate a variety of polyphenols, which you can do by eating a variety of food sources. As we observed earlier (in the “What are polyphenols?” section of the first article of this series), polyphenols come in many different forms. Different polyphenols have different structures, are absorbed at different points in the digestive tract (or not absorbed at all), and are metabolized by different bacteria. Inevitably, this leads to different biological outcomes, and it is often mentioned in the literature that the health effects are polyphenol-specific (Cardona et al., 2013; Del Bo et al., 2019; Durazzo et al., 2019; Pandey & Rizvi, 2009). These differences in biological effects of polyphenols may explain some of the inconsistencies that can be found in the literature when reading on polyphenols and various health outcomes, especially if studies do not differentiate between the compounds but group them together under the label “polyphenols” (Zhou, 2017). Regardless, since the health effects of polyphenol consumption appear to be net positive, it makes sense that rotating between different polyphenol-rich foods — especially those with a good reputation, such as berries, coffee, cocoa, and green and black teas — allows you to obtain various benefits across different areas of health. Both with myself and with clients, I like to have somewhat of a checklist to keep some accountability on this. I emphasise daily (or at least 4–5x weekly) consumption of the following foodstuffs:
· Green tea
· Coffee, due to caffeic acid and caffeine (for certain cognitive benefits caffeine is required)
· Berries (particularly blueberries and blackberries)
· Turmeric, always combined with black pepper. Piperine (a component of black pepper that has decent health properties on its own) enhances the absorption of curcumin (a component of turmeric with excellent health properties) by 2000% (Hewlings & Kalman, 2017).
· Cinnamon (ideally not exceeding 1g due to coumarin content)
· Cacao
· Cruciferous vegetables (a group that includes broccoli, kale, sprouts, cabbage, and cauliflower, amongst others), combined with mustard seeds. Aside from being valuable as a food source for other reasons, they contain a compound, glucoraphanin, which can be converted to another compound, sulforaphane, which has great potential for excellent health properties (Houghton, 2019). This requires the activity of an enzyme, myrosinase, which is heat insensitive. Since most of these vegetables are consumed cooked, we supply mustard seeds, which contain myrosinase, to ensure this conversion still takes place and that we can still reap the benefits of sulforaphane in the body.
· Garlic, due to sulphur-containing compounds like allicin
· Ginger, mostly due to gingerols
Additionally, after learning what I have whilst reading for this article, I will add to this list grapes, cranberries and black tea, since these were some that stood out repeatedly across multiple studies as being particularly beneficial for health.
Another interpretation of this information could be to selectively utilise polyphenols that have a desired health outcome in a targeted approach. For example, if I was to find out that some polyphenol had a significant positive impact on skeletal muscle hypertrophy, there’d be no doubt I’d be consuming it breakfast, lunch and dinner (actually caffeic acid of coffee does have this effect, as shown by Jang and colleagues (Jang et al., 2018), but I already drink a sufficient amount of coffee and the effect is probably rather small). In other circumstances, you may be particularly vigilant to certain health states such as cancer, for which curcumin of turmeric is renowned (Giordano & Tommonaro, 2019), or weight management and obesity-induced metabolic aberrations, for which green tea may be chosen(Cardona et al., 2013; Van Hul & Cani, 2019), or gastrointestinal function, for which gingerols of ginger are thought to be effective (Anh et al., 2020). If you’d like to manage inflammation for the purposes of general health, recovery from illness, cardiovascular and metabolic protective effects, or anti-aging purposes you may choose foods rich in resveratrol, such as red wine and grapes, since resveratrol has a particularly good reputation for this (Cardona et al., 2013; Pandey & Rizvi, 2009).
It seems appropriate to mention at this point, however, that for some of these foods or polyphenols effect sizes will not be large. In some cases, for a significant effect to be seen, regular consumption over long periods of time may be required. This is not always the case — recall the study of Moreno-Indias that saw significant microbiota changes with only 272ml of red wine over a 60-day period (Moreno-Indias et al., 2016) — but I feel compelled to add this disclaimer because it is possible that any impact on your health may be largely sub-perceptual. This shouldn’t be too discouraging, though; changes in health tend to occur due to the action of sustainable lifestyle changes that lead to small effects on the short scale that amount to tangible effects over the long term. This is why it’s important to find ways to incorporate healthy changes (such as the consumption of polyphenol-rich substances) into your life in a way that is natural and easy, rather than in a way that is laborious and therefore unsustainable. To this end, find polyphenol-rich foods and drinks that you like and make it a habit to consume them regularly. With so many to choose from, it’s hard to imagine that there’ll not be any that you can get acquainted with.
Other Points of Interest
One thing I thought worth mentioning is that some polyphenols only exert certain health effects in specific subpopulations. We’ve established that the microbiota is responsible for a significant portion of the health effects observed following polyphenol consumption. However, the microbiota represents a point of meaningful variability between individuals (Kirk et al., 2021). Thus, it follows that the same polyphenol consumption between different individuals leads to different effects on the microbiota and different proportions of polyphenolic metabolites entering the plasma and the tissues, leading to different health outcomes (Cardona et al., 2013). A well-known example of this is the bacterial metabolism of soy isoflavone daidzein. Whilst some individuals metabolize this isoflavone to one metabolite (d O-desmethylangolensin), others metabolize it to another (equol). By measuring which of these metabolites is present in the system following consumption of soy products, phenotypes can be established. These phenotypes may have associations with health outcomes, namely cardiometabolic outcomes: equol producers appear to derive cardioprotective effects from soy product consumption, whereas d O-desmethylangolensin producers do not (Frankenfeld, 2017). Without knowing which type you are, this information is not so actionable for now. It does, however, partially explain the discrepancies seen in studies on polyphenols and health outcomes, meaning. Studies often use average to draw conclusions about treatment effects. However, this may mask subpopulation specific effects. That is, effects occur in one subgroup but are absent in another, meaning taking an average will just appear to present an effect size in the middle of the two, hiding the reality of what is really going on. As we enter the age of personalized nutrition, in the near future we might have more clarity on how food choices impact us on an individual (or adequately stratified) level. For more on this, see my article on the topic (Kirk et al., 2021).
Adverse Effects of Polyphenols on Health
Most of the literature on polyphenols focuses on their health benefits. There are a few reasons for this. The first is probably simply because most polyphenols found in common founds tend to have a net positive effect on our health. Another is because foods with polyphenols in them that do have adverse effects on health tend to be shielded from us, not sold in supermarkets, and not commonly eaten. Another reason, however, is that researchers often set out to look for positive results. This is not unethically motivated, but more that researchers are interested in the health benefits of foods, and this motivates them to find out more about these benefits. This is an issue not just on polyphenol research or even nutrition research, but in science in general. Positive findings are viewed more favourably and receive more attention than negative findings. And within a group of compounds as large and diverse as polyphenols, it is not surprising that some do have some adverse effects.
One of the most famous examples of polyphenols and adverse health outcomes is that of phytoestrogens in soy. Although some of these effects are desirable (for example, in the treatment of some prostate cancers (Ajdžanović et al., 2019; Applegate et al., 2018; Goetzl et al., 2007; Hamilton-Reeves et al., 2013; Perdana et al., 2016; Vaishampayan et al., 2007)), many people (especially men) avoid soy in fear of oestrogen enhancing effects. This is largely unjustified since soy products seem to offer protective effects on health (such as on prostate cancer or cardiovascular function) whilst imposing minimal health concerns (Goetzl et al., 2007; Messina, 2016). Conclusions on biological outcomes are often derived from animal studies which are not always translatable to humans or utilise doses that would be unrealistic in a human diet. Studies do not find hormonal alterations due to soy consumption (Hamilton-Reeves et al., 2013; Reed et al., 2021). As Messina puts it in his 2016 review on the topic: “Evidence indicates soyfoods can be safely consumed by all individuals except those who are allergic to soy protein”.
In a 2005 review, Mennen et al. provide various examples of polyphenols exerting various negative effects mostly in animal studies (Mennen et al., 2005). This information is valuable but should be taken in the context of the entire body of literature as well. For example, it is mentioned that quercetin has been shown to have carcinogenic properties, however, this is in stark contrast to results seen elsewhere (Pandey & Rizvi, 2009). As the authors proceed to mention, and we saw above with soy, it is likely that unrealistically high doses are used in in vitro or animal models, causing effects that would not occur under normal circumstances. For example, they write: “It is possible that the genotoxic effects observed in vitro may be attributable to the high concentrations used, at which polyphenols may become prooxidants”. In the essence of completeness on my part, though, I do feel it necessary to describe some other of these negative findings. Quercetin also negatively impacted rat kidney health and limited mouse life expectancy. Caffeic acid — at a level of 2% of the diet! — caused kidney and stomach tumours of rats and mice, and green tea catechins at 1% or 0.1% of the diet enhanced tumour development in the colon of rats. Some flavonoids have negative associations with thyroid function, though maybe only in the context of iodine deficiency. Another review also describes adverse effects from certain polyphenol-rich beverages in those with pre-existing health conditions, namely degenerative disease, high blood pressure, thyroid disease, epilepsy, or heart disease (Cory et al., 2018). Of course, this has to be balanced with the fact that polyphenols could indeed be protective against certain of these diseases, as we have seen in previous sections. Hence, these findings should be assessed on an individual basis, with regards to the person and the polyphenol in question. In cases of doubt, the person in question should discuss this matter with health experts such as their doctor.
An example where negative effects of polyphenols are of legitimate concern is the antinutritional effect they can have. Certain polyphenol compounds can have negative effects such as binding to nutrients or inhibiting enzymes of the digestive tract, thus interfering with nutrient absorption. Phenolic compounds like tannins can inhibit proteases and thus interfere with protein absorption, reducing uptake by fairly small but significant amounts. Phenolic compounds can limit nutrient bioavailability such as via properties such as metal chelating activities, reducing uptake of components like calcium, iron and zinc (Samtiya et al., 2020). Thus, populations at risk of deficiency of these compounds and also consuming many crops high in phytates should pay special attention to circumvent this issue (Cory et al., 2018).
The topic of antinutrients was partially a focus of mine on some work I did for a recent internship, and so I spent quite a lot of time reading about this topic. My conclusion was, and still is, that these are mostly concerns for animal farmers; for humans consuming foods within reasonable amounts, these are not valid issues. If you did think you might be at risk of nutritional deficiency because of the antinutritional effects of certain polyphenols, a rather easy fix for this would be to simply consume a little more of the nutrients you think you’re at risk for. This is the exact approach I take for myself. Since I rarely consume animal products, I am aware that the bioavailability of the protein I consume is lower, and therefore I consume a little more (~2.5g/kg of body weight/day instead of 1.8–2.2g/kg of body weight/day) to account for this.
A final significant concern may also be interaction with medicines (Mennen et al., 2005). This is a concern not just for polyphenols but all substances that enter your body. You should be aware of potential interactions and your doctor should inform you of this whenever you begin new treatments.
I don’t believe in glorifying the health effects of nutritional approaches, as unfortunately tends to happen often. It’s exciting to learn about the positive effects that foods can have but you should also be aware of potential harms. Having said that, the body of evidence tends to favour a positive effect of polyphenol consumption and certainly suggests these outweigh any potential negatives, especially when polyphenol-rich foods are not consumed in excessive amounts.
Conclusion
Due to the focus on macronutrients, vitamins, and minerals over the last few decades, it can be easy to forget about other components of the food matrix, such as polyphenols. Although not essential — you won’t die anytime soon without them — they clearly have a positive impact on health, and it’s likely you’ll live longer and healthier with them. Fortunately for us, polyphenols are found in many different natural and delicious foodstuffs, making them pretty easy to obtain. Explore different foods, be sure to rotate between ones you like, and make use of ones with particularly outstanding reputations. And if you ever need a reminder of which ones they are and what they do, you can always fall back on this series to help you!
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