The UK General Election is around the corner so in order to make some of the manifesto promises of each party more digestible (and sciencey), I used The Guardian's Policy summaries with a science twist! Just how would each political party run your brain? Scroll through to find out!

If you are unsure who to vote for, check out The Guardian link or do your political compass to give you an idea of which party aligns most with your views. Happy voting!

Updated: Jul 24, 2020

A morning routine is a unique experience. While some naturally rise with the sun others hit snooze repeatedly; vowing to never stay up binging an entire Netflix series again. But whether you are an early or not-so-early bird, one action is pretty unanimous in the pre-work-up prep: coffee. The caffeinated beverage which can be drank hot or cold, sipped or shotted, black or white, seated or to go, with a general purpose to boost your alertness first thing in the a.m. But have you ever thought about how coffee acts on your brain to make you feel fast instead of fatigued? And what about the long-term consequences of your consumption of Joe on your neurons and co? Research into the action of caffeine, other active chemicals in coffee and the brain have uncovered interesting links between coffee and cognition, including lessening neurodegenerative diseases (*a clickbait article enters cyberspace*). But just how true are the claims that drinking coffeee is neuro-protective?

The Chemistry of Coffee

When you request your venti flat white with soya milk and sugar-free vanilla syrup, the barrister in Starbucks may seem like a wizard; concocting the perfect cup of poison to send that much-needed wake-up call to your brain. You are not wrong for feeling like sipping the life-giving liquid is a magical experience as brewing coffee is just like a potions class. Each little bean which goes into your cup contains a particular blend of chemicals which gives coffee its smell, taste and, most importantly, its kick. The A+ conical of coffee contains 1000s of different chemicals which contribute towards it’s aroma, known-antioxidant compounds called chlorogenic acids as well as the stimulating caffeine. In isolation, some of coffee’s chemicals are supposedly able to induce ‘drunk states’ in rats (2-Ethylphenol) and treat symptoms of asthma (Theophylline). Despite the complex actions of the many compounds present in coffee, the dose received in a single cup aren’t quite up to rendering you above the driving limit.

Once you gulp down your hot concoction, some of the coffee chemicals are able to pass from your digestive system into your blood and up to your brain, and the chemical responsible for exerting an alertness effect is caffeine. Caffeine (aka 1,3,7-trimethylxanthine - so catchy) wakes you up by binding to receptors on the surface of neurons which normally bind a chemical called adenosine. Adenosine is a chemical compound which builds up in your brain throughout the day and binds to adenosine receptors to inform neurons of your tiredness. Then more adenosine bound, the sleepier you feel until you are so overcome with tiredness, you fall asleep. Overnight, this adenosine is cleared and the build-up can begin again the next day. Caffeine competes with adenosine to bind to some of these receptors in the brain, and when caffeine latches on, it stops ‘sleepiness' signals being sent. Caffeine can hang around in the body for hours after finishing your cup so having a late-evening latte might disrupt your sleep - with adenosine waiting in the wings for caffeine clearance before being able to take you off to the land of nod.

Cognition and Caffeine

As coffee is such a widely-consumed, physco-active beverage, the effect it has over time on your brain has been studied in human populations and in laboratory set-ups. Too much caffeine in one sitting is correlated with unpleasant actions such as anxiety-like behaviours and headaches, which you will know if you’ve had to pull an all nighter before a deadline and used an excess of coffee to keep sleepy-time at bay. However, high intake of coffee over time has been associated with some cognitive benefits in several studies, including enhanced working memory in rats when they were fed approximately 10 cups worth of coffee per day. Similar relationships have been drawn in large-scale studies of people who consume high levels of caffeinated drinks, however other human studies have reported no such relationship. Isolating the effects of coffee when its intake is ingrained into everyday life amongst a myriad of other influential variants, such as diet, is tricky. Plus, coffee’s known short-term impact on alertness, arousal and mood could also contribute to a temporary elevation in working memory rather than actually enhancing long-term memory potential.

Research has also focused on the impact of coffee intake and the development of disease, including disorders of the brain. In two studies published over the past year, the relationship between specific chemicals in coffee and their potentially alleviating affects on neurodegenerative-associated mechanisms have been explored. Research by scientists at the University of Toronto found phenylindane, a compound in coffee, was capable of reducing the aggregation of Alzheimer’s disease associated proteins (amyloid-beta and tau) in the lab. Large protein aggregates in the brain are a hallmark of many neurodegenerative disease, therefore a hypothesised therapeutic mechanism is to prevent this aggregation happening; and a coffee compound looks like it can do that in a dish. Further to this bench-top work, another research group from Rutgers Robert Wood Johnston Medical School assessed the therapeutic impact of co-administering Eicosanoyl-5-hydroxytryptamide (EHT), another coffee-chemical, and caffeine to mice which present with Parkinson’s-like symptoms and a-synuclein pathologies, seen in Parkinson’s patients, later in their lifespan. The results of the experiment showed giving the animals EHT and caffeine lead to improved behavioural performance of these mice as well as amelioration of some of the pathological hallmarks they usually acquire with age by ’switching off’ a specific gene (PP2A). This lead to a conclusion that coffee has the potential to prevent the Parkinson’s-mediated neurotoxicity.

Could coffee intake reduce neurodegeneration?

Studies such as those above do imply there are chemicals in coffee which could protect against mechanisms we believe to be crucial in neurodegenerative cascades. However, conclusions cannot be jumped to. Both of these studies were not done in human’s. The first was performed with pure protein in test tubes, which while good for testing protein-protein interactions, cannot inform us of the physiological interactions between these proteins when in the human brain - a completely different chemical environment. Although the second study was done in mice, representing a more ‘real’ environment for these interactions, the mice were genetically modified to hugely over-express a-synuclein - a non-physiological phenomenon which could alter the way proteins in the brain interact. Laboratory tests are vital in these types of studies, but strong conclusions cannot be made until mechanisms are confirmed in humans.

In addition, the dose of ‘coffee’ will also hugely impact these potentially-protective interactions. A favourite saying of the amazing Insta-chemists I interact with is ‘the poison is in the dose’ and the same concept applies to reducing pathological events using chemicals. In the mouse study above, mice were fed 50mg/kg of caffeine per day. If you translate this into human weight, I, a 59kg woman, would have to get almost 3000 mgs of caffeine per day - equating to over 30 cups of average coffee (95mg of caffeine per cup). Unless I want to be a shaking mess, there is no chance I am coming close to 30 cups of coffee each day. A lot of these studies hugely up the 'regular’ dose - which is fine for proving an interaction has the potential to happen and cause an effect, but physiologically, this is a lot harder to interpret.

Finally, we are still not 100% sure on what mechanisms cause neurodegeneration. Both of these studies rely on the hypothesised mechanisms of protein aggregates found in the diseases being causative agents in mediating neurodegeneration. Caffeine and other coffee-based chemicals may interact with these aggregate-forming proteins and even prevent their formation, but we still do not know if this would definitely help stop neurodegeneration. Plus, as mentioned, other factors such as diet and genetics could vary our response to coffee’s mechanisms within the brain. This research points towards a potentially positive effect on caffeine intake and neuroprotection but many more large-scale, properly controlled human studies need to be conducted before we can stamp the neuroprotective label on this well-loved beverage.

Overall, when you read coffee-based research, leave the sugar and take your joe with a pinch of salt.




A splash of extra reading

Main Papers

Mancini et al (2018). Phenylindanes in Brewed Coffee Inhibit Amyloid-Beta and Tau Aggregation. Front. Neurosci. Vol 12.

Yan et al (2018). Synergistic neuroprotection by coffee components eicosanoyl-5-hydroxytryptamide and caffeine in models of Parkinson's disease and DLB. PNAS. 115 (51)

Background Lit

The Chemistry in every cup

Here's everything that's hiding in your cup of coffee

A review of caffeine’s effects on cognitive, physical and occupational performance

Habitual coffee consumption and cognitive function: a Mendelian randomization meta-analysis in up to 415,530 participants

Is caffeine a cognitive enhancer?

Updated: Jul 25, 2020

Have you ever felt so worried that you can’t eat a thing? Or stress-binged an entire packet of biscuits while revising for an exam? If you have experienced an emotionally-driven digestion dilemma, it will come as no shock to you that your brain and your gut are engaged in a dialogue. In fact, your gut actually has an entire nervous system dedicated to it’s functioning, as well as central nerves which permit signals from your brain to reach the pit of your stomach. Although we know these systems communicate, interests lie in how much they influence each other. In this realm lies the emerging link between the composition of the microorganisms in the gut and neuropsychiatric disorders, namely anxiety and depression. Recent population studies of both conditions in humans indicate a difference, and therefore potential therapeutic target, in the gut microbiome - bringing a whole new meaning to your 'gut feeling'.

Gut feelings: Normal chat between your brain and belly

You may have felt that lurch in your stomach after realising you accidentally clicked ‘Reply All' with a cat meme on a full staff email. The anxiety-associated sinking feeling is produced from brain signalling to your gut. Although the gut has its only independent nervous system (the Enteric nervous system), the brain also connects to the digestive system through several pathways of neuron projections; with each pathway having individual origins in the brain and different chemical-mediated actions. Two of these pathways include the autonomic nervous system (ANS) and the hypothalamic pituitary axis (HPA). The ANS is responsible for those ‘automatic’ functions we don't even have to think about doing, such as breathing, heartbeat and controlling all that digestive movement you get after eating a bangin' meal. The HPA is responsible for regulating the levels of ‘stress’ hormones in your system, spiking following a tense sitch. The origins of these pathways in the brain are from the hormone centre (the hypothalamus) and the fear area (the amygdala), who both receive their directions from ‘high-thinking’ emotional brain regions such as the pre-frontal cortex. So although the gut mainly acts in an automatic manner, stress and emotions readily can impact the motion of the mucosa.

But what about you stomach talking to your brain? Your gut is able to reply to your brains actions and also signal *BRAND NEW INFORMATION*. One of these communication lines is sensory neuron afferents (*dendrites*) in the gut. Signalling to the brain via neuron projections can be stimulated by normal and abnormal gut movements (mechanical stimulation), the immune system and chemical changes within the digestive system; sending signals to the brain stem and spinal cord. This information is then relayed to various brain regions, for example, to the hypothalamus, which reports to higher cortical regions on the current state of the digestive system. Gut-mediated signalling is also received at behavioural and emotional centres such as the amygdala, the anterior cingulate cortex (thought to be responsible for complex cognitive processes like empathy & impulse control) and the orbitofrontal cortex (an area associated with decision making), as well as reward centres which can release dopamine in response to eating; generating a positive-association with this behaviour. Together, gut signalling can influence your state of mind and behaviour, not just how you digest your dinner.

Digestion-driven depression? Studies of the depression, anxiety and the gut microbiome

One major area of human biology research in recent years has been focused on the composition of the gut microbiome; thousands of different microorganisms responsible for protecting your health and fighting disease laying low in your stomach. Every individual has a distinct gut microbiome influenced by their genetics and environmental factors, and the composition of this microbiome can be altered by factors such as stress, diet and infections. However, alterations to the levels of certain species could potentially have a much great impact on human mental health than anticipated. It is thought gut microorganisms can influence signalling of neural afferents in the gut via the release of vitamins, neurotransmitters and metabolites, and specific bacterial species within the gut can impact the activity of specific brain regions and circuits. Mice bred to have no ‘germs’ in the gut display learning defects and reduced anxiety-like behaviour, highlighting the impact the gut microbiome can have on higher cognitive behaviours. Mouse models with symptoms mimicking depression and anxiety can have these symptoms lessened by treatment with specific gut bacterium (Lactobacillus Rhamnosus) and germ-free mice can have depressive symptoms induced when fed microbiome samples from human patients with depression. These studies along with a body of others promote the idea depression and anxiety in mammals can be impacted by the microorganisms in the gut.

So what about in humans with mental health conditions such as depression and anxiety? Recent population studies of both conditions drew correlations between gut microbiome composition and the mental health disorder in question. Researchers from KU Leuven-University compared the microbiome composition of over 2000 people and could relate the presence and levels of specific bacteria species with likelihood of the individual having depression. Individuals with high levels of Faecalibacterium and Coprococcus bacteria were described as having a higher quality of life, whereas lower levels of of Dialister and Coprococcus bacteria were noted in those with depression. Similar relationships were drawn in a review of studies which attempted to treat anxiety using microbiome-altering medication. The reviewers noted that over half of the 21 large-scale human studies conducted resulted in alleviation of anxiety symptoms. They pointed out that non-probiotic (e.g. dietary changes) interventions were more affective treatments than probiotic (giving more gut bacteria) supplementation. Together, these studies draw correlations with alterations to the microbiome and changes in mental health, with potential for specific micro-organism treatment or diet alterations as therapeutics dependent on the individual and the condition from which they are suffering.

Could modulations of the gut cut mental health?

From the above research, we could think of the gut microbiome as a world filled with trillions of individuals performing several thousand different occupations. Some of these occupations may be more beneficial to the world than others, so having more of these skilled individuals could promote a more prosperous environment, whereas other occupations which are not as useful are needed at lower numbers. However, if you lose too many of the important workers and gain a few million of those who are less helpful, your upset balance could lead to huge problems with optimal output. But, a key aspect of this scenario we need to full understand is which jobs are important and why. Although specific bacterial species have been linked with depressive and anxious symptoms, it still remains unclear how these species induce such complex states in the brain and it is unlikely they do so alone. Some gut bacteria are known to influence specific brain circuits and alterations to neurological processes, such as Lactobacillus' alteration to inhibitory neuron receptors, have been noted. Potentially, the recognition of the full neurological and health impact of these species could lead to the development of non-invasive mental health treatments targeting the gut by screening the gut microbiome and altering levels of specific bacterial species with the goal of lessening debilitating mental states.

The real work now will be to classify how many thousands of gut microorganisms alter neuronal or neural network functioning. This will require in-depth biological studies of individual and combinations of microorganisms as well as confirmation of results in large scale human studies. Once we have these answers, maybe we can truly go with our guts for mental health therapeutics.




What do you think of this link between the gut and mental health? Hit me up on my socials for a discussion!

Hungry for more? Links to full articles below

Main Paper: Valles-Colomer et al (2019). The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology. volume 4, pages 623–632

Gut feelings: the emerging biology of gut–brain communication

Relationship between the gut microbiome and brain function

Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

Gut microbiome remodeling induces depressive like behaviors through a pathway mediated by the host’s metabolism.

Effects of regulating intestinal microbiota on anxiety symptoms: A systematic review