Friday, 6 February 2015

Flavonoids


What are they?
Flavonoids are a subcategory or type of polyphenol, which are also referred to as phytonutrients. There are over 4000 identified flavonoids, and they are sometimes split into further subcategories: flavones, flavonols and flavonones.  They cannot be created by the human body.  For the sake of this post I’m not going to be addressing each individual flavonoid or subcategory (unless a study has used a specific flavonoid, in which case it’s only ethical I name it).  The reason is threefold: 1 life is short and I’m far from being educated enough to delve into thousands of individual compounds 2. Flavonoids are something I don’t think we need to supplement with, as they are abundant in a variety of foods 3. Foods contain a plethora of these plant pigment powerhouses, and the main message I want to convey is that we need to eat more fruit and vegetables in a variety of colours.  They serve a number of processes in the body as they are antioxidants and anti-inflammatory.  These processes have been associated with several health benefits and disease preventions.  


Antioxidant Action
This is the biggie!  Foods and food products are always being marketed for their antioxidant content, but why is this important? What’s it actually doing within the body?  In a nutshell an antioxidant prevents other molecules from being oxidised.  To get a real understanding of this we need to dig a little deeper into the biochemistry.  The first thing to know is what exactly a free radical is.  A free radical is a molecule with an unpaired electron.  The fact is has an unpaired electron makes it unstable and highly reactive.  To rectify this it “attacks” the nearest stable molecule “stealing” an electron from that molecule and thus turning that molecule into a free radical.  This can cause a cascade effect and result in the disruption of a living cell.  Picture a child losing his favourite toy so he goes and steals his friends toy, if this chain of events carries on soon the whole playground is crying and going crazy.   An antioxidant is a child who is happy to give up their toy to the first child and prevent any negative situation from occurring.  This is because antioxidants are stable with paired or unpaired electrons.  Free radicals occur as a result of normal everyday metabolism and immune function, but increased levels are produced as a result of cigarette smoke, pollution and radiation.  So essentially antioxidants help prevent cell damage and death.

Anti-Inflammatory
It is theorised that flavonoids play a role in managing inflammation.  Most of the experiments into this theory are in cellular models (so in the lab rather than on humans).  The mechanisms that have been identified, in these lab trials, link flavonoids to preventing the creation of pro inflammatory mediators (eicosanoids, cytokines, adhesion molecules and C-reactive protein).  It is important to bear in mind these trials took place in the lab. This is where it gets kind of fuzzy.  For example some lab trials will use astronomically high dosages to identify mechanisms.  There have been human trials, investigating this theory, which have thus far yielded positive, but less conclusive results.  These experiments have predominantly used increased consumption of flavonoid rich foods (tea, fruit, veg, cocoa etc.).  This type of method has positives and weaknesses.  From a really scientific point of view, it’s difficult to attribute the reduction in inflammation to just the flavonoids when you are using food.  This is because real food also has loads of vitamins, minerals and various other brilliant compounds, which could potentially be causing the positive effect.  On the other hand, the way I see this is, real whole foods, the stuff that we should be eating more of, are having an effect on inflammation.  To sum up this section there is some fairly strong evidence for flavonoids as an anti-inflammatory, but a bit more work on human trials needs to be done.  This is necessary to make a definitive conclusion to fully attribute the effect solely to them.

Effect on Health
Knowing these two mechanisms is great, but everyone wants to know what real world effects of getting enough flavonoids in our diet.

Heart Disease Incidence and Deaths
I looked at a review article that examined results from several large cohort studies.
4/7 studies found a statistically positive association with increased flavonoid intake and death from coronary heart disease.  Three of seven cohorts reported that greater flavonoid intake was associated with lower risk of incident stroke.  The flavonol and flavone classes were most strongly associated with lower heart disease mortality. The evidence for protection from heart disease from other flavonoid classes were more limited.

I want to take a break from flavonoids here and briefly explain what I mean by “association”, and the difference between association/correlation and causality.  You will often see media outlets run articles headlined by titles along the lines of “food product X cause/cures disease Y”.  This kind of title, in most cases, is very misleading as the studies they are based on make no claim to causality.  What can cause or protect us from disease is not black and white, as we don’t live black and white lives.  Everyone one of us has our own lifestyle and there are a plethora of factors that could influence what goes on in our body.  Cohort studies take a brief snapshot of a population in order to try and identify trends.  I will use this study on flavonoids and heart disease as an example.

So the people who consumed greater amounts of flavonoids had lower incidence of heart disease, that’s the general trend it seems.  But what if by chance those people also exercised more frequently, or had healthier diets too.  It’s difficult to label flavonoids as the single defining factor effecting their heart health, when we know there are lots of other potential contributors.  This is just a brief explanation, and as I have been writing this paragraph I think this topic needs a whole blog post, so stay tuned for that.  It’s something I feel quite strongly about as I seem to constantly encounter a clear lack of understanding, or negligence from the media when they report on nutritional/health science.  This muddies the water and leads to confusion.

Cancer
I don’t want to get too deep into cancer, as I don’t think it is really my place.  I have a bit of an understanding of the disease; however it’s extremely complex and I’m not a doctor.  That being said I have looked at some epidemiological studies regarding flavonoids and cancer.  I am going to use some direct quotes here, to make sure I’m not misinterpreting any studies.  All the articles and books I’m using will be listed at the end of the post.

It has been theorised that antioxidant compounds play a role in protecting us from cancer.  This is thought to be due to the mechanism I have explained, with flavonoids clearing up free radicals and reactive oxygen species.  To really get into the science the Mechanisms of action are: inhibition of proliferation, inflammation, invasion, metastasis, and activation of apoptosis (death of an infected cell).

The main review article I looked at  concluded that “Food flavonoids exert protective effects against various types of tumours including oral and pharyngeal, gastric, pancreatic, colorectal, hepatic, prostate, ovarian, endometrial, breast, and lung cancers.”  However it also stated that “Prospective studies with larger sample sizes are necessary to reduce bias and calibrate the effects of specific flavonoids and interactions on the cancer response.”

I also came across two nice studies from the European Prospective Investigation into Cancer (EPIC).  EPIC is a huge programme that currently has 521,000 participants.  It really is one of the most robust studies investigating cancer.  If you are interested here is a link to their website, check it out http://epic.iarc.fr/

In an 11 year follow up the group that consumed the most flavonols (one of the subclasses on flavonoids), had a lower rate of cancer incidence, compared to the group that consumed the least amount of flavonoids.  The risk association was 0.74.  This means they had 26% less cancer incidence.

Again in an 11 year follow up, incidence of gastric adenocarcinoma (A form of stomach cancer) was reduced, this time in association with total flavonoid consumption.  The incidence rate was lower in both men and woman, but only in women was the difference statistically significant.

 

Brain Function

A relatively new discovery is that flavonoids intake could impact our brains, potentially improving memory, learning and brain plasticity. 

There have been several studies linking flavonoid intake to the reversal of age related deficits in memory and learning.  A large number of these studies have used tea, cocoa and gingko biloba.  They have yielded positive results, however like the studies into heart disease and cancer it’s difficult to single out flavonoids as the single reason for this positive change.
A more recent study in mice, has actually identified a mechanism linking pure flavonols and anthocyanin with improved brain function.  Not only did the mice have improved spatial memory performance, the researchers saw a rise in the levels of a protein called brain derived neurotrophic factor (BDNF).  This protein promotes the survival of nerve cells (neurons)The BDNF protein helps regulate synaptic plasticity, which is important for learning and memory.  Even though this study is in mice it’s a big discovery, as we now have some mechanistic evidence to support the previous trials.  This evidence means that flavonoids could potentially be protective of neuro-degenerative disease, such as Alzheimer's and Parkinson's 


Here are two graphs from the study I have mentioned.  As you can see memory performance and levels of BDNF were much better in the various flavonoid groups (BB, A & F), compare to the control group (C).
Food
Let’s talk real food!  We now know loads about flavonoids but where do we get them in the diet?  The main source for most of us should be fruits and vegetables.  Flavonoids are just one of many reasons we need to pile out plates high with veges! Other common sources are tea, coffee, chocolate and red wine.  Obviously with those last three we need to think about moderation.  With chocolate it’s only the dark stuff that is rich in flavonoids so 70%+, personally I really like 85% dark chocolate it is awesome.  Whilst I have been reading, it seems to be the flavonol subclass that has the strongest links to health.  These include Kaempferol, myricetin and quercetin, rich sources are Onions, kale, broccoli, apples,
cherries, fennel, sorrel, berries and tea.

For me I think the easiest way to get more vegetables in to my diet is stir-frys, I eat loads of these.  They are quick and easy to make and there is so much you can do with in terms of flavours.  Soy sauce, ginger, garlic, chilli, lemongrass, honey, coriander are just a few things I like to throw in to add flavour.  Then all I need is some meat and maybe some grains or sweet potato and its game on. 
Here is my stir-fry of the day - chicken, broccoli, spinach, carrot, peas, sugar snap peas, garlic, soy sauce and mixed grains.  Beside it a cup of rooibos tea for some extra flavonoid power. 
Local Shops
Originally I was going to link in local fruit and veg suppliers, but I figured they could fit in with loads of future posts.  So I visited a couple of local shops seeing a big variety of tea, dark chocolate and coffee.

The Green Shop - 30 Bridge St, Berwick-upon-Tweed, Northumberland TD15 1AQ
01289 305566








The Market Shop - 48 Bridge Street, Berwick-upon-Tweed TD15 1AQ
01289 307749




Conclusion
Flavonoids are very strongly linked to a variety of health benefits.  They are powerful brain boosting, cancer fighting, molecules of marvel.  They are just one of hundreds of reasons why eating several portions vegetables, and maybe the odd glass of red wine, is really important for our health and well being


References
Geissler, C. and Powers, H. (2005). Human nutrition. Edinburgh: Elsevier/Churchill Livingstone.

Hodgson, J., Puddey, I., Mori, T., Burke, V., Baker, R. and Beilin, L. (2001). Effects of regular ingestion of black tea on haemostasis and cell adhesion molecules in humans. Eur J Clin Nutr, 55(10), pp.881-886.

Kumar, P. and Clark, M. (n.d.). Kumar & Clark's clinical medicine.

Mrak, R. and Griffin, W. (2007). Common Inflammatory Mechanisms in Lewy Body Disease and Alzheimer Disease. Journal of Neuropathology and Experimental Neurology, 66(8), pp.683-686.

Mukamal, K., MacDermott, K., Vinson, J., Oyama, N., Manning, W. and Mittleman, M. (2007). A 6-month randomized pilot study of black tea and cardiovascular risk factors. American Heart Journal, 154(4), pp.724.e1-724.e6.

Murphy, T., Dias, G. and Thuret, S. (2014). Effects of Diet on Brain Plasticity in Animal and Human Studies: Mind the Gap. Neural Plasticity, 2014, pp.1-32.

Nägga, K., Wattmo, C., Zhang, Y., Wahlund, L. and Palmqvist, S. (2014). Cerebral inflammation is an underlying mechanism of early death in Alzheimer’s disease: a 13-year cause-specific multivariate mortality study. Alzheimer's Research & Therapy, 6(4), p.41.

Ralph, A., Garrow, J. and James, W. (2000). Human nutrition and dietetics. Edinburgh: Churchill Livingstone.

Rendeiro, C., Guerreiro, J., Williams, C. and Spencer, J. (2012). Flavonoids as modulators of memory and learning: molecular interactions resulting in behavioural effects. Proc. Nutr. Soc., 71(02), pp.246-262.

Rendeiro, C., Vauzour, D., Rattray, M., Waffo-Téguo, P., Mérillon, J., Butler, L., Williams, C. and Spencer, J. (2013). Dietary Levels of Pure Flavonoids Improve Spatial Memory Performance and Increase Hippocampal Brain-Derived Neurotrophic Factor. PLoS ONE, 8(5), p.e63535.

Romagnolo, D. and Selmin, O. (2012). Flavonoids and Cancer Prevention: A Review of the Evidence. Journal of Nutrition in Gerontology and Geriatrics, 31(3), pp.206-238.

Ryu, O., Lee, J., Lee, K., Kim, H., Seo, J., Kim, S., Kim, N., Baik, S., Choi, D. and Choi, K. (2006). Effects of green tea consumption on inflammation, insulin resistance and pulse wave velocity in type 2 diabetes patients. Diabetes Research and Clinical Practice, 71(3), pp.356-358.

Steptoe, A., Gibson, E., Vuononvirta, R., Hamer, M., Wardle, J., Rycroft, J., Martin, J. and Erusalimsky, J. (2007). The effects of chronic tea intake on platelet activation and inflammation: A double-blind placebo controlled trial. Atherosclerosis, 193(2), pp.277-282.

Widlansky, M., Duffy, S., Hamburg, N., Gokce, N., Warden, B., Wiseman, S., Keaney, J., Frei, B. and Vita, J. (2005). Effects of black tea consumption on plasma catechins and markers of oxidative stress and inflammation in patients with coronary artery disease. Free Radical Biology and Medicine, 38(4), pp.499-506.

Zamora-Ros, R., Agudo, A., Lujan-Barroso, L., Romieu, I., Ferrari, P., Knaze, V., Bueno-de-Mesquita, H., Leenders, M., Travis, R., Navarro, C., Sanchez-Cantalejo, E., Slimani, N., Scalbert, A., Fedirko, V., Hjartaker, A., Engeset, D., Skeie, G., Boeing, H., Forster, J., Li, K., Teucher, B., Agnoli, C., Tumino, R., Mattiello, A., Saieva, C., Johansson, I., Stenling, R., Redondo, M., Wallstrom, P., Ericson, U., Khaw, K., Mulligan, A., Trichopoulou, A., Dilis, V., Katsoulis, M., Peeters, P., Igali, L., Tjonneland, A., Halkjaer, J., Touillaud, M., Perquier, F., Fagherazzi, G., Amiano, P., Ardanaz, E., Bredsdorff, L., Overvad, K., Ricceri, F., Riboli, E. and Gonzalez, C. (2012). Dietary flavonoid and lignan intake and gastric adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. American Journal of Clinical Nutrition, 96(6), pp.1398-1408.

Zamora-Ros, R., Sacerdote, C., Ricceri, F., Weiderpass, E., Roswall, N., Buckland, G., St-Jules, D., Overvad, K., Kyrø, C., Fagherazzi, G., Kvaskoff, M., Severi, G., Chang-Claude, J., Kaaks, R., Nathlings, U., Trichopoulou, A., Naska, A., Trichopoulos, D., Palli, D., Grioni, S., Mattiello, A., Tumino, R., Gram, I., Engeset, D., Huerta, J., Molina-Montes, E., Argaelles, M., Amiano, P., Ardanaz, E., Ericson, U., Lindkvist, B., Nilsson, L., Kiemeney, L., Ros, M., Bueno-de-Mesquita, H., Peeters, P., Khaw, K., Wareham, N., Knaze, V., Romieu, I., Scalbert, A., Brennan, P., Wark, P., Vineis, P., Riboli, E. and González, C. (2014). Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. British Journal of Cancer, 111(9), pp.1870-1880.


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