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Contains Cocoa and Caffeine

The very first article I wrote and published while a medical student showed international data linking coffee consumption with cancer of the pancreas. This is a nasty and usually fatal cancer that was increasing at the time in the West, and the data I found suggested coffee could be a cause. This paper was a real breakthrough, not for science, but for my CV and my research career, which took off as a result. As I said before, such ecological studies are usually flawed. The same analysis would have shown that owning a TV or flared trousers, the incidence of which had also increased in the same regions, was associated with the cancer, and the media headline would have been that it could have ‘caused’ it. And the same analysis would have shown that chocolate (cocoa) eating was deadly.

Anyway, another thirty years of similar bad science and media scare stories followed, along with hundreds of expensive research studies using observational data and overdosing poor old rats with coffee. A similar story emerged in the 1980s telling us that hormone replacement treatment was thought to be a miracle cure for everything from depression and heart disease to dementia and declining sex drive. I was one of those taken in. Only when clinical trials were performed did the risks of heart disease and cancer emerge and the benefits disappear, with the exception of preventing fractures. We have learnt lessons from past mistakes, but it often takes time to reverse old ideas and prejudices. The jury is now in as to whether coffee and its accomplice caffeine are guilty as charged, and whether chocolate and cocoa are really naughty but nice.

When our mid-year exams during our first year of medical school arrived, my friends and I were panicking one day about a tough biochemistry exam that we hadn’t prepared for. We decided we all needed to revise all night to stand a chance. We took caffeine (Pro Plus) tablets, which I knew would certainly keep me awake and alert and I was confident of a solid twelve hours of swotting before the exam. The reality was somewhat different. I was trembling and twitching and couldn’t concentrate or remember anything. Exhausted and lacking any facts worth mentioning, I failed miserably. I was wary of caffeine for many years after, and like most people believed that it and the other famous bean extract, cocoa, were bad for you.

Caffeine is probably the world’s commonest psychoactive drug, drunk by 80 per cent of the world. But it is addictive in many coffee drinkers, who develop shakes, attention problems and withdrawal headaches if they stop suddenly. The effects of complex foods like cocoa and coffee can now be studied more precisely. Our bodies contain thousands of circulating chemicals, metabolites, whose importance is reflected in how our cells function metabolically. We can now measure most of these individual chemical fingerprints quite precisely in just a drop of blood, saliva or urine with the science known as metabolomics. We have used this technique in our twins, with spectacular gene discoveries and new links to diseases, and of the 1,200 existing metabolite signatures that we can now identify in blood at least 250 are produced solely by our gut microbes.1

Several studies in humans have shown that microbes, probiotics and antibiotics can alter the levels of the key chemicals that are the precursors of brain neurotransmitters. These chemical signals, such as tryptophan and serotonin, play a pivotal role in the brain as well as in depression and anxiety. Most of the body’s hormone serotonin is produced in the intestines, and recently we have found it is mainly manufactured by microbes during times when we are not eating. Autism is increasingly and consistently associated with disordered microbes, and these could be the link with abnormal brain-chemical signalling.2

Is chocolate really a miracle food?

Studies showing the miraculous powers of chocolate are much loved by the media and the public, especially in the UK. We are third in the chocolate-eating league tables at 9.5 kg per person in 2012, behind only Ireland and Switzerland, and nearly double the US. The feel-good effects of chocolate are in part due to our gut microbes. In several studies, dark chocolate given to adults produced significant changes in the blood neurotransmitters and other metabolites that only microbes could have produced.3 There is also evidence that obese people are more sensitive to the alluring smell of chocolate than skinny ones.4 So if you like chocolate a bit too much, blame it on your microbes, who like to keep your brain happy.

Unlike with many other easy-target foods and additives, such as e-numbers, colorants, fats and burgers, the ‘chocolate is healthy’ stories are regular features in our newspapers. For instance, it is claimed to miraculously prevent or cure heart disease, cancer, depression, low libido and sexual dysfunction. The source of these acclaimed ‘special powers’ is a bean that is roasted and fermented. This is the fruit of the Theobroma cacao plant, literally ‘the fruit of the gods’ and supposedly first cultivated by the Aztecs. Most chocolate we eat is made up of sugar, fat, milk solids and cocoa beans. Culture and marketing determines the amount of milk and the percentage of cocoa in the mix.

There is considerable worldwide variation, but Anglo-Saxon countries generally prefer the milk variety, although dark chocolate consumption is increasing. While, in our twins, liking sweets and chocolate in general has a genetic basis, we found the preference for milk chocolate over dark was mainly cultural with little effect of genes. Within chocolate eaters, genes rather than culture played a greater role in whether you prefer hard or soft centres. This is likely due to genetic preferences for different textures as well as for sweetness.

Regardless of the media hype, the absence of long-term studies and my initial scepticism, the evidence is now pretty good, though not water-tight, that the cocoa in chocolate, which itself is made up of over three hundred chemical substances, is positive for reducing risk factors for the heart.5 A few, admittedly observational, studies have even suggested that regular consumption is associated with lower body weight.6 Over seventy human clinical studies and many more animal studies have been performed on cocoa.

Of the many chemicals in the substance, the constituents showing the clearest benefit are compounds known as flavonoids. These are part of the same polyphenol family found in nuts and olives that we discussed earlier, which has anti-inflammatory, antioxidant and important microbial effects.7 Gram for gram, cocoa has the highest concentration of polyphenols and flavonoids of any food, and it’s a precious commodity.

Chocolate eaters are often embarrassed to be questioned on the subject, and as with calorie and alcohol intakes, people are often ‘economical with the truth’ about their consumption. So as to avoid this, with colleagues in Norwich we looked at metabolomic markers in the blood of 2,000 of our UK twins. We found that twins with the highest blood-flavonoid levels coming from chocolate, berries and wine had lower weights, better arteries, lower blood pressure, stronger bones and a lower risk of diabetes.8 This all seems too good to be true – and it was observational – but it makes more sense when we consider the role of our microbes. In fact, there is now compelling evidence that our microbes, like us, enjoy chocolate. In the gut they play a major role in the metabolism of the chemicals from cocoa that lead to improvements in blood-lipid levels. When a British clinical trial gave volunteers the polyphenol extracts (flavonoids) from cocoa for four weeks, it saw significant increases in bifidos and lactobacilli and reductions in the Firmicutes family as well as in markers of inflammation.9

The authors of the trial report suggested these cocoa flavonoids could make a useful prebiotic supplement and the Web offers plenty of ways to buy them. High-grade cocoa can now be bought in health food shops, and confectionery giants like Mars are now marketing 250 mg cocoa flavonol supplements such as Cocoavia™ as powders to add to milk, oatmeal or smoothies.10 The downside is the extra 200 calories you need to ingest to get the benefits. The EU has approved a health claim from a Swiss chocolate company for a similar product, and many more will follow.

Less is known, however, about what happens in the real-life situation when you combine the cocoa with the sugar and saturated fat that you find in a normal chocolate bar, which most people regard as unhealthy. This was recently carefully tested in Swiss volunteers using 25 grams of a 70 per cent cocoa dark chocolate, twice a day for two weeks.11 Each serving (Nestlé Intense, since the study was sponsored by them) comprised also 6 grams of sugar and 11 grams of fat. The subjects ended up with no worsening of their total or bad (LDL) cholesterol and there was a significant increase in their good cholesterol (HDL), despite the extra fat. Another Swiss study of dark chocolate eaten for four weeks found improvements in blood vessels, but adding extra flavonols to the chocolate made no difference.12 Other studies showed similar beneficial short-term effects on lipids.

The microbes fed off the flavonoid polyphenols and produced many helpful by-products, like the healthy SCFA butyrate. What was striking was that after a week the amount of these polyphenol metabolites was greater than could be accounted for just from the diet. The microbes, once fed a bit of chocolate, were producing these healthy chemicals of their own accord, like little home industries. They also found that regular chocolate eaters had different and healthier metabolisms and microbes than occasional chocolate eaters.13

Beware the milky variety

So that’s fine if you like 70 per cent cocoa dark chocolate, but what if like most children, Brits and Americans you prefer your chocolate milkier, like Cadbury’s or Hershey’s? Is this kind helpful or harmful to your microbes and health? The UK market leader Cadbury’s Milk was launched in 1905 as the ‘first’ real milk chocolate (although this was likely invented in Germany in 1839). It now contains 26 per cent cocoa, plus cocoa butter, which is the mainly saturated fat coming naturally from the cocoa nut, cow’s milk and sugar. A small serving of four squares contains 4.7 grams of saturated fat and 14.2 grams of sugar (3½ spoonfuls). Cadbury’s milk chocolate used to contain 23 per cent cocoa, then increased it in 2013 because EU milk chocolate now has to contain real milk and at least 25 per cent cocoa. In the US you only need a miserly 10 per cent cocoa to call it chocolate. Hershey’s milk chocolate is only about 11 per cent cocoa and proportionally sweeter. Each serving contains 8 grams of fat and 24 grams of sugar (6 spoonfuls). Although milk chocolate uses the same type of cocoa as dark chocolate, to get the polyphenol benefits you need to eat three to five times more, and you’d likely get fat and lose your teeth in the process.

So training your taste buds to eat more than 70 per cent cocoa dark chocolate may be worthwhile in the long term. But working out your minimum daily dose is going to be difficult, as actual amounts of helpful flavonoids vary widely according to the manufacturing process. Some companies sneakily make the chocolate darker with additives and the percentage of cocoa stated is only a rough guide. Hopefully, flavonoids and polyphenols will soon be included on the food label.14

Food company scientists noticed decades ago that combining lots of fat and sugar together can produce near-addictive qualities. Add in the magical properties of chocolate, and it becomes irresistible. Most of the bestselling confectioneries use this formula and companies are continually trying to improve their blends so as to tease the consumer’s taste buds. One of the latest potential blockbusters was launched by Kraft foods after it merged with Cadbury’s to become the global leader. It is called Kraft Indulgence Spread, a mix of Kraft Philadelphia Cream Cheese with ‘real’ Belgian chocolate. It may be popular, but don’t expect highly processed foods like this to be microbe, polyphenol or waistline friendly. Returning to the Mediterranean paradox: residents of most of these countries – France, Spain, Italy – traditionally prefer strong dark (high-cocoa) chocolate to the milky and less healthy variety. This preference might well contribute to their better cardiac health, although it would be hard to prove.

Caffeine can let you down

Michael Bedford was at a party near his home in Mansfield, Nottinghamshire. He ate two spoonfuls of caffeine powder he’d legally bought online, and washed them down with an energy drink. He began slurring his words, then vomited, collapsed and died. He had ingested more than 5 grams of caffeine, equivalent to about fifty espressos. The coroner cited caffeine’s ‘cardiotoxic effects’ as the cause of death. He was twenty-three years old. Caffeine is not always harmless fun.

The soft drinks companies add caffeine routinely to enhance taste, complexity and bitterness and give the drinks a kick, especially in diet colas lacking real sugar. Levels in a can of Pepsi and Coca-Cola have reduced in recent years, as some parents complained of overexcited insomniac kids. Levels vary between the US and Europe, with higher levels in the US. Pepsi Max contains 43 milligrams in the UK and 69 in the US; Coke, 32 mg here and 34 mg in the US; Diet Coke, 42 mg and 45 mg. Other drinks companies like Red Bull (80 mg) make caffeine a part of their appeal to all-night-partiers needing ‘energy’. Most regular fizzy drinks average around 30–45 mg, about half that of a normal coffee or the same as a mug of weak tea.

Companies add caffeine to most drinks officially for flavour and complexity, but unofficially to improve their addictive properties on top of the already powerful fructose. Tea contains variable amounts of caffeine (20–70 mg) but usually has half that of coffee per serving, and strength is unrelated to colour. Unsurprisingly, among the UK media, tea always had great PR and was blessed with medicinal properties. The publicity seemed to be backed up with reasonable epidemiological data from a summary of twenty-two prospective studies showing a 25 per cent reduction in mortality for those drinking two to four cups a day, dropping off above that amount.15 The caveat is that benefits seem to be only for green-tea drinkers rather than black-tea lovers, as in the UK.

The unpredictable espresso hit

In the UK coffee has replaced tea as the commonest beverage, and the success of the coffee franchises around the world suggests this is part of a global addiction. Caffeine and its main beverage coffee have come under a huge amount of scrutiny and suspicion and have been the target of many media scare stories. Caffeine has been linked with increasing stress, poor sleep and long-term heart disease and cancer. It is very hard for people to know how much caffeine they are drinking with each cup of coffee as there are no standards. A UK study of twenty espresso bars found a nearly fourfold difference in the caffeine in a single espresso shot, which could be as high as 200 milligrams, the recommended upper limit for pregnant women. There was found to be even a large daily variability in samples from the same coffee bar, and between countries a tenfold variation in a single shot.

The lack of a standard cup of coffee explains the unpredictable effects, and an Italian can still sometimes be surprised by the strength of an American brew.16

It turns out, though, that drinking even six cups of coffee per day overall is not harmful for most people. Combining twenty-one individual prospective studies of the coffee habits of over a million people from Europe, the US and Japan that were followed for several years until 128,000 of them had died, provided powerful data. It showed that moderate coffee drinking, three or four cups per day, reduces the risk of death by around 8 per cent and heart disease by 20 per cent. Unlike my own, inferior, analysis, there was no effect either way on cancer.17

Although we should still be wary of epidemiological data because other linked habits of coffee drinkers (such as drinking alcohol or smoking) could be responsible for the findings, since a long-term clinical trial forcing people to drink coffee is an unlikely eventuality these estimates are as good as we will get. A few people with sensitive hearts should avoid extra caffeine, but for most of the two billion people who drink it daily it appears beneficial.

So if coffee really is good for us, why might this be? It is addictive and in excess can cause anxiety, poor sleep and heart arrhythmias. In the UK we are still wary of it and mainly because of the caffeine content.

The cocoa plant evolved to produce caffeine in large amounts mainly to fend off predators nibbling at its leaves, where the highest concentrations are found, and to give it room to spread out in the surrounding soil. It may be that some susceptible animals became addicted to the caffeine, kept returning for another nibble, and spread the seeds around. Geneticists have recently found that the cocoa plant and humans share an important characteristic: their genes. Cocoa actually has more protein-coding genes (25,000) than humans (around 20,000), which should improve our view of the evolution of coffee – or lower our view of humans.18

Scare stories still come out about potential carcinogens in different types of coffee and in the bean-roasting process.19 Caffeine is just one of thousands of chemicals the beans contain, and numbers increase further on roasting. Most internet accounts misleadingly focus on the properties of just one single ingredient out of the thousands. Arabica coffee contains at least twelve different polyphenol compounds, the commonest of which has a nasty name conceivably more appropriate to swimming pools – chlorogenic acid. However, so far we think that most of the polyphenols, like those in cocoa and olives, even if they sound toxic are actually beneficial to us.

We performed our twin studies to show that preference for coffee, as for many foods, is under strong genetic influence.20 This may be partly to do with taste genes, but collaborating with another team in a gene-association meta-analysis we found these preferences depended on different specific genes which control the way coffee and its thousands of chemicals are processed by the liver. The good or bad feelings we get from complex foods like coffee are also dependent on the chemicals that our bodies produce when our enzymes break down the food product; in other words, it could affect people differently.21

As well as the thousands of chemicals and the dozen antioxidant polyphenols, coffee has the surprisingly high fibre content of half a gram per cup. This combination of fibre and polyphenols permits it also to provide food for our gut microbes.22 Microbes break down the fibre to produce the key short-chain fatty acids like butyrate, which allow other helpful Bacteroidetes and Prevotella species to increase.23 So coffee wakes our microbes up in the mornings, and it’s not just the caffeine that does it.

What happens if you don’t like espressos or strong brews? In the US you may need the jumbo pint-sized portion to get enough polyphenols, but our microbes seem nearly as happy drinking the polyphenols in decaffeinated or freeze-dried instant varieties if the doses are equivalent. The same may not be true for tea lovers. Although tea contains some polyphenols it lacks the extra fibre of coffee, and small differences could explain the absence of benefit from black tea. For those who don’t like to wake up to the smell of actual coffee, there is some evidence, if scanty, of a potential for weight loss if you use green coffee bean extract as a supplement.24

The stories about foods and drinks such as coffee that transform them from villain into hero and vice versa should make us all more wary of accepting at face value the evidence of any common food as deadly or as a miracle cure. Nevertheless, it is comforting that our current knowledge strongly suggests that our habit over thousands of years of consuming cocoa and coffee may not be harmful, and may even be a good thing. But can the same be said of the demon drink?