John (Long John) Daly was a lucky guy. It was 1991 and he had just got his professional golf association card and was sitting at home in Arkansas when the phone rang. He was on a waiting list of nine others to see if anyone dropped out of the PGA tournament. It turned out that a golfer’s wife had delivered a baby early and he rushed home. The other eight hopefuls on the list above him couldn’t make it in time. He flew to the course, borrowed a caddy and without even playing a practice round found himself ahead of the field. Against all the odds he eventually won the tournament. The rookie was an instant crowd favourite for his lack of etiquette, big hitting and carefree attitude. He went on to win the British open in similar style. But then his inner demons took over and he stopped winning.
He began overeating, he couldn’t control his alcohol intake and his performances suffered. He was also addicted to cigarettes (forty a day) and lost millions of dollars of his earnings on gambling. In his forties, after his coach left him with the parting line ‘The most important thing in your life is alcohol’, he went into rehab. He gave up alcohol and replaced it with Coke, then put on weight and changed to Diet Coke, then quickly became addicted to that as well, but his weight stayed the same.
A year later he had a gastric-band operation so as to lose weight. But, he complained, ‘The band won’t allow me to drink as many. If I don’t have ice, I can’t drink it. I can’t have it straight because of the carbonation. I used to have twenty-six to twenty-eight cans a day. Now I have ten to twelve at the most.’ He still plays golf and attends the US Masters, but only to sell his merchandise from a bus next to his office – the Hooters’ Diner, known for its scantily clad young waitresses.
‘Diet’ drink addictions like John Daly’s, or for the ‘real thing’ with sugar, are increasingly common and certainly a cheaper habit than alcohol or cocaine, but they have disastrous results on the body’s metabolism. Clearly, Daly’s problems didn’t go away when he changed from regular to diet drinks. Most cases like this don’t qualify as a full-blown chemical addiction as he didn’t have documented withdrawal symptoms. He just had the powerful urge to keep drinking more.
Artificial sweeteners – not the free lunch we once thought
Diet drinks appeared to be the ultimate modern invention when Diet Pepsi was launched, first in the US in 1963 and twenty years later in the UK. Not just the idea but the consumption of non-caloric sweeteners in foods has been around for a hundred years. An increasing number of people particularly turn to diet drinks with near zero calories to try to avoid the effects of sugar and reduce weight.
Not everyone likes diet drinks. Some people with over-sensitive taste buds and certain gene variants find the artificial taste strong and unpleasant. Others dislike the aftertaste. Some of the distaste is also due to the fact that we are very sensitive to the different textures and structures of the chemicals in the drink that are trying to mimic the taste of the sugary equivalent. The carbonation is another factor that can trick the brain into thinking a product is less sweet than it really is.1 Flat cola is often undrinkable.
Since the 1980s diet drink sales have steadily increased globally. By 2014 they accounted for a third of total US sales and a $76 billion market. But the saccharine tide is turning. Growing public concerns about the health effects of the sweetener chemicals – particularly fears about cancer – have seen US sales drop since 2010, and European markets are likely to follow as people switch to caffeinated energy drinks. Most people, however, believe non-caloric artificial sweeteners are good for losing weight. Short-term studies in which overweight kids are switched from regularly drinking sugary drinks to artificial sweeteners are usually reported as being beneficial for weight loss. If you look closely, though, you see the results are not as clear-cut as you might expect, considering the substantial calorie differences.
The largest of these studies so far was performed on 641 Dutch children randomised to drinking a can of either diet or regular cola a day for eighteen months.2 Both groups continued to gain weight over time. The diet cola group certainly gained less weight than the regular cola group, but not dramatically less, and the average weight gain of the diet group was disappointingly more than expected, with only minimal differences in feelings of fullness compared to the sugar group.3
A number of observational but longer-term studies have shown associations in the sweetener group with weight gain and diabetes, even after controlling for the fact that heavier people are more likely to use sweeteners in the first place.4 5 This could partly be explained as long-term psychological effects that alter behaviour. In another study 114 students were randomised to drink regular Sprite (a sugary lemonade), Sprite Zero containing aspartame, and sparkling water as a control. They showed that the diet drink altered some aspects of the students’ future behaviour that made them seek extra calories and suggested the chemical had effects on the brain.6
This may not be so crazy. Aspartame, a key ingredient of the world’s most used sweetener, can affect the brain cells of the hypothalamus and in theory upset appetite pathways.7 8 Other studies have shown that the reward pathways in the brains of habitual diet drinkers have altered so that they get a greater kick out of sugar.9 These chemical molecules that tickle and trick our taste receptors out of calories are now in many of the foods and drinks we consume and hard to completely avoid.
The world’s most flexible sweetener used in food, soft drinks and alcohol has the friendly name Sucralose, but it is actually the less catchy 1,6-dichloro-1,6-dideoxy-β-D-fructofuranosyl-4-chloro-4-deoxy-α-D-galactopyranoside. It used to be thought of as an inert chemical possessing five hundred times the sweetness of sugar that passed straight through the body and sailed through safety tests for cancer. But although there is no good evidence – as opposed to public opinion – for linking its use with cancer, as usual there is more to the story.
Several studies have now shown that ‘inert’ Sucralose alters hormones involved in digestion. It does this by activating the taste receptors, which as well as being on the tongue are also found on the pancreas, in the gut and in the hypothalamus. Small human studies of obese patients show this leads to increased insulin release, increased gastric emptying and the release of normal digestive hormones such as GLP-1.10 Sucralose also alters liver enzymes in rodents that in humans can modify how we respond to a common array of drugs.
Sweeteners are clearly not ‘inert’. Digestively they arrive largely untouched in the colon, where they can interact with our microbes. There appears to be a good degree of individual differences in how we respond to sweeteners, which could be down to our microbe communities. Some evidence of this came from early studies in 2008 looking at just a few microbes in rats. Researchers fed rats Splenda (Sucralose) at the FDA-recommended human doses for twelve weeks, and found significant reductions in total microbe counts and diversity, and in particular this affected the healthy microbes.11 The gut was also made more acidic. Some of these changes were sustained for up to three months after the drinks stopped. An observational but detailed diet study of 98 subjects, although not designed for the purpose, suggested for the first time that there could be an association between aspartame intakes and changes in microbe contents in humans.12
Alkaline diets and our microbes
Interest in trying to change the acidity of the gut via diet has waxed and waned in the world of nutrition, but was rekindled when Alkaline diets became popular. The theory is that if you reduce acidic foods you can make the gut less acidic and the blood more alkaline and ‘healthy’. As before, regarding other explanations involving the body’s acids, the theory is rubbish. The gut is naturally designed to be very acidic to digest food and the blood is kept slightly alkaline. The body controls the blood acidity very tightly via your kidneys and urine, so diets can’t affect it. But as many of the constituents of the Alkaline diet are vegetables and it involves avoiding meat, this diet myth may have some inadvertent benefits.
One of my PhD students, Madison, ‘volunteered’ for a short study to monitor her gut microbes as they received first a Coke then a Diet Coke. The plan was to get baseline results, then have three days of the real thing, sugar Coke, drinking 1.5 litres a day of it, followed by three days of Diet Coke, then just water for three days. Analysing one person is problematic, and some of her samples had to be redone because the sequencing, as in real life, doesn’t always work perfectly. Madison was happy when we looked at the results, as they showed very high levels of the rare (and tough to pronounce) microbe family Christensenellaceae that we found to be protective for obesity in our twins study. But she shouldn’t have worried because she is fit and lean anyway. However, we also found surprising changes on the Diet Coke days, which showed an increase in the diet-responsive microbe Bacteroidetes that was hard to interpret.
Try taking antibiotics with your diet drink
Luckily, at around the same time an Israeli group led by Eran Elinav had a similar idea but did the study on a much grander scale and published their findings in the journal Nature. First, they found that giving normal supplement doses of three common sweeteners (Sucralose, aspartame or saccharine) to mice on normal or fat diets produced a significant increase in blood-glucose levels compared to the sugar-consuming mice. They repeated the test with antibiotics to kill off any effect of microbes, and this completely removed any effect of the sweetener.
Next, by transplanting them into the germ-free mice and producing the same glucose increase in the new animals, the researchers showed that the gut microbes were directly responsible. They then looked at the microbes of forty people participating in a nutrition study who regularly consumed sweeteners compared to 236 who didn’t. They found exactly the same effects as in the mice: namely, abnormal blood-glucose and insulin levels. They then set up another study in which seven sweetener virgins were given saccharine supplements (at normal approved levels) for seven days on top of a standard controlled diet while having their blood glucose monitored.
Although people responded differently, four out of seven experienced major changes, including increases in Bacteroidetes and quite a few unusual gut microbes, which mirrored their glucose changes. The sweeteners induced the microbes to overproduce two of the metabolic signallers we mentioned previously, the short-chain fatty acids (SCFAs), but unusually these did not include the healthy butyrate. Overall, the function of the new microbial team was ramped up by the sweeteners to digest carbs and starch more efficiently than before. This would affect their digestion of normal food, which in turn could explain the weight gain.
This elegant series of experiments shows that artificial sweeteners are definitely not a free lunch; they do have potentially harmful metabolic effects that can increase weight gain and the risk of diabetes. They do this because even so-called inert chemicals can be crucial for our microbes, which change their function and so affect our bodies. We don’t yet know the true extent of the risk of the sweeteners and whether everyone is susceptible, but these microbe experiments have made sure that we and our food regulators who approve the new ‘safe compounds’, once they pass the cancer tests, should now take these risks more seriously.
Manufacturers of diet drinks and many processed foods, because they lack the natural anti-bacterial effect of sugar, compensate by adding large numbers of chemical preservatives such as sodium or potassium benzoate, citric acid or phosphoric acid. Many of these, including the benzoates, tartrazine, MSG, nitrites and nitrates, are commonly reported as causes of allergy. The same chemicals are also likely to be having major unsuspected influences on our microbes by potentially reducing their numbers and their diversity. They also affect our immune systems, both directly and via interactions with our microbes.13 This has been suggested as another reason for the recent rise of allergies. Most of the chemical safety-testing of food additives and sweeteners focuses on determining the risks of poisoning or cancer, not on detecting metabolic changes in our bodies. So until we know more, maybe we should be reducing or, ideally, avoiding these ‘harmless’ chemicals.
The global rise of chemical sweeteners in drinks and foods looks as if it is slowing down as some of the public turn back to natural products. But as noted earlier, the downside is that this usually means using more sugar. The soft-drink companies are trying to keep up with health-conscious customers by using – since 2011 in the EU – the sweet stevia leaf as a ‘natural’ alternative to sweeteners. It is claimed to reduce calories by 30 per cent. Because of its cost it is usually mixed with cheap sugar. It allegedly has no downsides, but by the time you drink this latest miracle sweetener in a manufactured drink, it has been heavily chemically processed; some people, though, can still detect its aniseed-like taste.
But what about natural stimulants that have been used for millennia – are they as bad?