Dr Priscilla Day-Walsh (Next Generation Fellow, Loke Centre for Trophoblast Research, University of Cambridge & Bye-Fellow, Homerton College University of Cambridge)
Chocolates or flowers for Valentines?
How about an apple?! Both apples and chocolates are considered gifts from gods. After all, the Trojan war would never have happened were it not for an apple being offered to Aphrodite in return for “the love of the world’s most beautiful woman; Helen of Sparta” by Paris of Troy (1). The heroine Atlanta ended up marrying Hippomenes after being distracted by three apples when her intention was to avoid marriage at all cost (2)!
Perhaps the best portrayal of an apple as a symbol of love is the Venus Verticordia painting by the pre-Raphaelite artist Dante Gabriel Rossetti. Rosetti depicted Alexa Wilding, “a remarkably handsome cook whom he met in the street”, as Venus holding a golden apple in her left hand and Cupid’s arrow pointing towards her heart in her right hand (3)(4).
Chocolate was of more value than gold to the Aztecs. They would use it as a currency as well as celebratory food in religious ceremonies and weddings and offer it as prizes to warriors after their return from a battle (5). These days chocolate is eaten on various occasions, in sadness as well as happiness or at Formal dinners as comfort when an experiment fails and in celebration of published manuscripts and secured grants! It turns out that it’s not just us who love apples and chocolates, the microbes in our gut do too and with part of their apple/chocolate digesta we are able to keep the doctors away.
Polyphenols not the Trojan War
While research in the Kroon group at the Quadram Institute is not about the Trojan war or Pre-Raphaelite brotherhood art, we are nevertheless fascinated by the power of apples and chocolates to mend broken hearts. Our research helps to explain what makes chocolate and apples important to our health and wellbeing! Bioactive compounds such as polyphenols found in apples and chocolate have been shown to play a key role in maintaining a healthy physiological homeostasis (6)(7). Polyphenols are naturally occurring bioactive compounds which include anthocyanins and proanthocyanidins also found in berries, vegetables and nuts as well as black rice and wine. Epidemiological studies have shown that individuals eating diets rich in polyphenols are at a lower risk of developing cardiovascular disease (CVD) and the associated co-morbidities (8). CVD has become an epidemic bringing a huge socio-economic burden worldwide. The advent of COVID-19 infection caused by the severe acute respiratory syndrome (SARS) coronavirus has highlighted the role of CVD co-morbidities in infections, hospitalisation and death (9).
What causes a broken heart (or CVD)?
Under normal physiological conditions, lipids are cleared away from the body into the liver by an apoprotein (ApoA-I) found on high-density cholesterol (HDL-c). In the liver lipids such as cholesterol are converted to bile acids and transported to the gut for further metabolism by the gut microbiota and subsequently excreted from the gut. CVD is caused by the accumulation of oxidised low-density lipoprotein cholesterol (LDL-c) in immune cells called macrophages which with the help of adhesion molecules migrate and accumulate in blood vessels causing inflammation and forming a fatty plaque called an atheroma. After some time, an atheroma can become unstable and rupture. As blood moves through the vessels, the ruptured debris can clog narrow vessels where they obstruct blood flow resulting in heart failure or stroke. Therefore LDL-c is known as bad cholesterol and HDL-c as good cholesterol.
Polyphenols can mend a broken heart
Our research and that of others have shown that polyphenols can lower the levels of LDL-c and increase the levels of HDL-c and as such, they enhance the capability to clear lipid-laden macrophages from blood vessels (10)(11). Polyphenols also target cellular signalling pathways that are involved in inflammation and attenuate platelet activity whilst increasing factors involved in blood pressure regulation such as nitric oxide 6. It is noteworthy that polyphenols may be the most effective when consumed in the context of whole food rather than as isolated compounds (12).
Polyphenol “Microbe hunters”
In order to understand the protective effects of polyphenols, we have also become “Microbe hunters”: The parent compounds that are ingested when we eat polyphenol-rich foods are detected at very low levels in the blood, suggesting that they are metabolised in the gut by the gut microbes and that the beneficial effects we get are due to microbial metabolites (13). Our work also aims to characterise the microbiota responsible for the production of these beneficial compounds and develop foods that increase the growth of such bacteria. Recent epidemiological data also suggest that some microbes can use up nutrients that are essential to physiological function and produce toxic substances that may lead to the development of CVD co-morbidities and are predictive of death from heart failure (14). We have recently started to characterise the capacity of individuals to produce these proatherogenic compounds and whether the microbiome of those at risk of producing high levels of these compounds can be modified by polyphenols to prevent CVD. We further aim to develop functional food with high levels of polyphenol derived beneficial metabolites.
Broken hearts can also develop in-utero. Research by Dr Priscilla Day-Walsh at the Loke Centre for Trophoblast Research, University of Cambridge aims to understand how microbial derived compounds affect the mother, the placenta and the fetus and how this relates to pregnancy outcomes and the infant’s lifelong health.
So perhaps the question should be “chocolates or apples for Valentines?”
- They are tasty
- They can improve mood and cognitive function
- They can protect you from a broken heart and keep you away from the hospital
Finally, eat responsibly! The darker the chocolate the better, both apple skins and flesh are good for you!
References
(1) Frazer., J. G.: Apollodorus. “E.3.2” Theoi Project. . In The Library Epitome.
(2) (1644–1717), N. C.: Hippomenes and Atalanta. Nicolas Colombel: Liechtenstein Museum, Vienna, Circa 1680.
(3) Rossetti, D. G. R., William Michae: Dante Gabriel Rossetti – His Family Letters with a Memoir; Roberts Brothers.: Boston, 1895; Vol. Vol.1. pp. 243.
(4) Rossetti, D. G.: Venus Verticordia. 1864 and 1868.
(5) Sophie D. Coe, M. D. C.: The True History of Chocolate; THAMES & HUDSON: New York, 2019.
(6) Ozyel, B.; Le Gall, G.; Needs, P. W.; Kroon, P. A. Anti-Inflammatory Effects of Quercetin on High-Glucose and Pro-Inflammatory Cytokine Challenged Vascular Endothelial Cell Metabolism. Mol Nutr Food Res 2021.
(7) Chambers, K. F.; Day, P. E.; Aboufarrag, H. T.; Kroon, P. A. Polyphenol Effects on Cholesterol Metabolism via Bile Acid Biosynthesis, CYP7A1: A Review. Nutrients 2019, 11, 2588.
(8) Arts, I. C.; Hollman, P. C. Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr 2005, 81, 317s-325s.
(9) Nishiga, M.; Wang, D. W.; Han, Y.; Lewis, D. B.; Wu, J. C. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nature Reviews Cardiology 2020, 17, 543-558.
(10) García, L. C.; Hernández, A. N. M. Beneficial effects of cocoa and dark chocolate polyphenols on health. The FASEB Journal 2020, 34, 1-1.
(11) Bondonno, N. P.; Bondonno, C. P.; Ward, N. C.; Hodgson, J. M.; Croft, K. D. The cardiovascular health benefits of apples: Whole fruit vs. isolated compounds. Trends Food Sci Tech 2017, 69, 243-256.
(12) Hollands, W. J.; Tapp, H.; Defernez, M.; Perez Moral, N.; Winterbone, M. S.; Philo, M.; Lucey, A. J.; Kiely, M. E.; Kroon, P. A. Lack of acute or chronic effects of epicatechin-rich and procyanidin-rich apple extracts on blood pressure and cardiometabolic biomarkers in adults with moderately elevated blood pressure: a randomized, placebo-controlled crossover trial. Am J Clin Nutr 2018, 108, 1006-1014.
(13) Corrêa, T. A. F.; Rogero, M. M.; Hassimotto, N. M. A.; Lajolo, F. M. The Two-Way Polyphenols-Microbiota Interactions and Their Effects on Obesity and Related Metabolic Diseases. Frontiers in Nutrition 2019, 6.
(14) Suzuki, T.; Yazaki, Y.; Voors, A. A.; Jones, D. J. L.; Chan, D. C. S.; Anker, S. D.; Cleland, J. G.; Dickstein, K.; Filippatos, G.; Hillege, H. L.; Lang, C. C.; Ponikowski, P.; Samani, N. J.; van Veldhuisen, D. J.; Zannad, F.; Zwinderman, A. H.; Metra, M.; Ng, L. L. Association with outcomes and response to treatment of trimethylamine N-oxide in heart failure: results from BIOSTAT-CHF. Eur J Heart Fail 2019, 21, 877-886.
