Is the link between flavonoid consumption and longevity cause-and-effect, and are all sources of flavonoids equally healthy?
How to Get Enough Polyphenols for Life Extension
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
Polyphenols are among the frontrunners in developing dietary approaches to fight age-associated disease. There is such a critical mass of data in favor of the protective benefits of these “lifespan essentials” that recommended daily intakes of polyphenols have been proposed. More than 8,000 different polyphenols have been identified, though only a small proportion have had their health effects cataloged. Shared structural features make them among the most powerful dietary antioxidants in vitro, but in our bodies, mechanistic effects have been attributed to their ability to modulate cellular signal transduction pathways.
In the PREDIMED trial, those in the top fifth of polyphenol intake had a 37 percent reduction in all-cause mortality compared to those in the lower fifth of consumption, which over an adult lifetime could translate into about four more years of life. However, the high-polyphenol group was eating nine servings of fruits and vegetables a day, compared to the five a day eaten by the low-polyphenol group; so, it’s possible there were other phytonutrients at play. Coffee and tea are major sources, but in terms of foods, polyphenols come primarily from vegetables, fruits, then beans.
There are about a half dozen different types of polyphenols, including phenolic acids like the curcumin in turmeric or the lignans concentrated in flaxseeds. But the largest class are the flavonoids. Plant eaters may consume more than 4,000 different types of flavonoids on a daily basis. Flavonoids include the anthocyanin pigments in berries, the isoflavones in soy foods, the catechins in tea (like EGCG), the flavonones in citrus, and the flavonols, like quercetin and fisetin, which people get from foods like apples, onions, and strawberries.
Like polyphenols generally, those who consume the most flavonoids tend to live significantly longer, according to a meta-analysis of 16 cohort studies following nearly a half-million people for five to 28 years. However, those who get more are also more likely to be college-educated, non-Hispanic white, with a higher income. The sharpest socioeconomic gradient was found for berry flavonoids. If you look at individual foods, though, as Harvard researchers did in the Nurses’ Health Study II, it wasn’t just blueberries and strawberries that were correlated with a lower risk of premature death, but also more affordable produce, such as apples and bell peppers.
To prove cause and effect, researchers randomized middle-aged men and women to eat higher-or lower-polyphenol diets in the Polyphenol Intervention Trial. Eight weeks later, the higher-polyphenol diet group enjoyed significant improvements in quality of life—both physically and mentally—compared to the lower-polyphenol diet group. But what did the two diets consist of? The lower-polyphenol diet group was told to restrict fruits and vegetables to no more than two servings a day, whereas the higher-polyphenol group was to eat six servings (including a portion of berries), plus two ounces (60 g) of dark chocolate a day. So, it could have been any number of fruit and vegetable components besides polyphenols responsible for the benefit. Just the enforced chocolate consumption might have boosted well-being! A more rigorous study design might be to randomize both groups to the same number of high-versus-low-polyphenol fruit and vegetable servings.
In the Nurses’ Health Study, you may have noticed that one food source of flavonoids was associated with an increased risk of all-cause mortality: grapefruit. Frequent grapefruit consumers were more likely to die prematurely than their non-grapefruit-eating compatriots matched for a large number of demographic and lifestyle factors. This was partly chalked up to grapefruit’s suppression of a set of detoxification enzymes in our intestines that may metabolize half the common drugs on the market. Broccoli has the opposite effect, boosting detox enzymes such that some drugs can be cleared faster, whereas even a single cup (240 ml) of grapefruit juice can reduce the rate of drug clearance for days, increasing the risk of potentially life-threatening drug side effects. That’s why grapefruit has been called a “pharmacologist’s nightmare.” If you’re on medications (including many common heart and blood pressure pills), make sure to talk to your prescriber about your grapefruit habits.
Please consider volunteering to help out on the site.
- Sharma R, Padwad Y. Perspectives of the potential implications of polyphenols in influencing the interrelationship between oxi-inflammatory stress, cellular senescence and immunosenescence during aging. Trends Food Sci. 2020;98:41-52.
- Del Bo’ C, Bernardi S, Marino M, et al. Systematic review on polyphenol intake and health outcomes: is there sufficient evidence to define a health-promoting polyphenol-rich dietary pattern? Nutrients. 2019;11(6):1355.
- Williamson G, Holst B. Dietary reference intake (DRI) value for dietary polyphenols: are we heading in the right direction? Br J Nutr. 2008;99 Suppl 3:S55-S58.
- Kennedy DO. Polyphenols and the human brain: plant “secondary metabolite” ecologic roles and endogenous signaling functions drive benefits. Adv Nutr. 2014;5(5):515-533.
- Tresserra-Rimbau A, Rimm EB, Medina-Remón A, et al. Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial. BMC Med. 2014;12:77.
- Spiegelhalter D. Using speed of ageing and “microlives” to communicate the effects of lifetime habits and environment. BMJ. 2012;345:e8223.
- Huang Q, Braffett BH, Simmens SJ, Young HA, Ogden CL. Dietary polyphenol intake in US adults and 10-year trends: 2007-2016. J Acad Nutr Diet. 2020;120(11):1821-1833.
- Si H, Liu D. Dietary antiaging phytochemicals and mechanisms associated with prolonged survival. J Nutr Biochem. 2014;25(6):581-591.
- Ivey KL, Jensen MK, Hodgson JM, Eliassen AH, Cassidy A, Rimm EB. Association of flavonoid-rich foods and flavonoids with risk of all-cause mortality. Br J Nutr. 2017;117(10):1470-1477.
- Khan N, Syed DN, Ahmad N, Mukhtar H. Fisetin: a dietary antioxidant for health promotion. Antioxid Redox Signal. 2013;19(2):151-162.
- Mazidi M, Katsiki N, Banach M. A greater flavonoid intake is associated with lower total and cause-specific mortality: a meta-analysis of cohort studies. Nutrients. 2020;12(8):2350.
- Kontogianni MD, Vijayakumar A, Rooney C, et al. A high polyphenol diet improves psychological well-being: the Polyphenol Intervention Trial (PPhIT). Nutrients. 2020;12(8):2445.
- Owira PM, Ojewole JA. The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives. Cardiovasc J Afr. 2010;21(5):280-285.
- Hakooz N, Hamdan I. Effects of dietary broccoli on human in vivo caffeine metabolism: a pilot study on a group of Jordanian volunteers. Curr Drug Metab. 2007;8(1):9-15.
- Shang DW, Wang ZZ, Hu HT, et al. Effects of food and grapefruit juice on single-dose pharmacokinetics of blonanserin in healthy Chinese subjects. Eur J Clin Pharmacol. 2018;74(1):61-67.
- Goldbart A, Press J, Sofer S, Kapelushnik J. Near fatal acute colchicine intoxication in a child. A case report. Eur J Pediatr. 2000;159(12):895-897.
- Owira PM, Ojewole JA. The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives. Cardiovasc J Afr. 2010;21(5):280-285.
Motion graphics by Avo Media
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
Polyphenols are among the frontrunners in developing dietary approaches to fight age-associated disease. There is such a critical mass of data in favor of the protective benefits of these “lifespan essentials” that recommended daily intakes of polyphenols have been proposed. More than 8,000 different polyphenols have been identified, though only a small proportion have had their health effects cataloged. Shared structural features make them among the most powerful dietary antioxidants in vitro, but in our bodies, mechanistic effects have been attributed to their ability to modulate cellular signal transduction pathways.
In the PREDIMED trial, those in the top fifth of polyphenol intake had a 37 percent reduction in all-cause mortality compared to those in the lower fifth of consumption, which over an adult lifetime could translate into about four more years of life. However, the high-polyphenol group was eating nine servings of fruits and vegetables a day, compared to the five a day eaten by the low-polyphenol group; so, it’s possible there were other phytonutrients at play. Coffee and tea are major sources, but in terms of foods, polyphenols come primarily from vegetables, fruits, then beans.
There are about a half dozen different types of polyphenols, including phenolic acids like the curcumin in turmeric or the lignans concentrated in flaxseeds. But the largest class are the flavonoids. Plant eaters may consume more than 4,000 different types of flavonoids on a daily basis. Flavonoids include the anthocyanin pigments in berries, the isoflavones in soy foods, the catechins in tea (like EGCG), the flavonones in citrus, and the flavonols, like quercetin and fisetin, which people get from foods like apples, onions, and strawberries.
Like polyphenols generally, those who consume the most flavonoids tend to live significantly longer, according to a meta-analysis of 16 cohort studies following nearly a half-million people for five to 28 years. However, those who get more are also more likely to be college-educated, non-Hispanic white, with a higher income. The sharpest socioeconomic gradient was found for berry flavonoids. If you look at individual foods, though, as Harvard researchers did in the Nurses’ Health Study II, it wasn’t just blueberries and strawberries that were correlated with a lower risk of premature death, but also more affordable produce, such as apples and bell peppers.
To prove cause and effect, researchers randomized middle-aged men and women to eat higher-or lower-polyphenol diets in the Polyphenol Intervention Trial. Eight weeks later, the higher-polyphenol diet group enjoyed significant improvements in quality of life—both physically and mentally—compared to the lower-polyphenol diet group. But what did the two diets consist of? The lower-polyphenol diet group was told to restrict fruits and vegetables to no more than two servings a day, whereas the higher-polyphenol group was to eat six servings (including a portion of berries), plus two ounces (60 g) of dark chocolate a day. So, it could have been any number of fruit and vegetable components besides polyphenols responsible for the benefit. Just the enforced chocolate consumption might have boosted well-being! A more rigorous study design might be to randomize both groups to the same number of high-versus-low-polyphenol fruit and vegetable servings.
In the Nurses’ Health Study, you may have noticed that one food source of flavonoids was associated with an increased risk of all-cause mortality: grapefruit. Frequent grapefruit consumers were more likely to die prematurely than their non-grapefruit-eating compatriots matched for a large number of demographic and lifestyle factors. This was partly chalked up to grapefruit’s suppression of a set of detoxification enzymes in our intestines that may metabolize half the common drugs on the market. Broccoli has the opposite effect, boosting detox enzymes such that some drugs can be cleared faster, whereas even a single cup (240 ml) of grapefruit juice can reduce the rate of drug clearance for days, increasing the risk of potentially life-threatening drug side effects. That’s why grapefruit has been called a “pharmacologist’s nightmare.” If you’re on medications (including many common heart and blood pressure pills), make sure to talk to your prescriber about your grapefruit habits.
Please consider volunteering to help out on the site.
- Sharma R, Padwad Y. Perspectives of the potential implications of polyphenols in influencing the interrelationship between oxi-inflammatory stress, cellular senescence and immunosenescence during aging. Trends Food Sci. 2020;98:41-52.
- Del Bo’ C, Bernardi S, Marino M, et al. Systematic review on polyphenol intake and health outcomes: is there sufficient evidence to define a health-promoting polyphenol-rich dietary pattern? Nutrients. 2019;11(6):1355.
- Williamson G, Holst B. Dietary reference intake (DRI) value for dietary polyphenols: are we heading in the right direction? Br J Nutr. 2008;99 Suppl 3:S55-S58.
- Kennedy DO. Polyphenols and the human brain: plant “secondary metabolite” ecologic roles and endogenous signaling functions drive benefits. Adv Nutr. 2014;5(5):515-533.
- Tresserra-Rimbau A, Rimm EB, Medina-Remón A, et al. Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial. BMC Med. 2014;12:77.
- Spiegelhalter D. Using speed of ageing and “microlives” to communicate the effects of lifetime habits and environment. BMJ. 2012;345:e8223.
- Huang Q, Braffett BH, Simmens SJ, Young HA, Ogden CL. Dietary polyphenol intake in US adults and 10-year trends: 2007-2016. J Acad Nutr Diet. 2020;120(11):1821-1833.
- Si H, Liu D. Dietary antiaging phytochemicals and mechanisms associated with prolonged survival. J Nutr Biochem. 2014;25(6):581-591.
- Ivey KL, Jensen MK, Hodgson JM, Eliassen AH, Cassidy A, Rimm EB. Association of flavonoid-rich foods and flavonoids with risk of all-cause mortality. Br J Nutr. 2017;117(10):1470-1477.
- Khan N, Syed DN, Ahmad N, Mukhtar H. Fisetin: a dietary antioxidant for health promotion. Antioxid Redox Signal. 2013;19(2):151-162.
- Mazidi M, Katsiki N, Banach M. A greater flavonoid intake is associated with lower total and cause-specific mortality: a meta-analysis of cohort studies. Nutrients. 2020;12(8):2350.
- Kontogianni MD, Vijayakumar A, Rooney C, et al. A high polyphenol diet improves psychological well-being: the Polyphenol Intervention Trial (PPhIT). Nutrients. 2020;12(8):2445.
- Owira PM, Ojewole JA. The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives. Cardiovasc J Afr. 2010;21(5):280-285.
- Hakooz N, Hamdan I. Effects of dietary broccoli on human in vivo caffeine metabolism: a pilot study on a group of Jordanian volunteers. Curr Drug Metab. 2007;8(1):9-15.
- Shang DW, Wang ZZ, Hu HT, et al. Effects of food and grapefruit juice on single-dose pharmacokinetics of blonanserin in healthy Chinese subjects. Eur J Clin Pharmacol. 2018;74(1):61-67.
- Goldbart A, Press J, Sofer S, Kapelushnik J. Near fatal acute colchicine intoxication in a child. A case report. Eur J Pediatr. 2000;159(12):895-897.
- Owira PM, Ojewole JA. The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives. Cardiovasc J Afr. 2010;21(5):280-285.
Motion graphics by Avo Media
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How to Get Enough Polyphenols for Life Extension
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