The bitter truth is sweeter than we thought

(image © Achim Schleuning / CC-BY-SA-4.0)

Cocktail bitters like Angostura and Peychaud’s have pedigrees going back to the 1830s. Looking like something out of a Victorian apothecary these intriguing botanical preparations may indeed have medicinal properties deeper than anyone thought.

Following our recent infographic (Health Hack #1: An alternative to fizzy drinks) in which I recommended using Angostura bitters as a basis for a healthy fizzy drink, I felt I had more to say about bitters in general.

In traditional herbal medicine, bitter herbs were considered aids to digestion through stimulation of bile and digestive juices. Taken fifteen minutes before a meal they were used to increase appetite –  the concept behind the idea of the aperitif – or after a meal as a digestive, but they are also thought to stimulate and ‘detoxify’ the liver, and generally are considered a ‘tonic’ to revivify the blood and to ‘enhance the vigour’ of the digestive system. Such vague and ill-defined terminology has led to these claims being largely dismissed. However, recent research is not only confirming the health value of bitter tasting substances but discovering that they have important physiological effects throughout the body.

The story of herbal bitters just took a fascinating turn that is proving to be sweeter than anyone might have imagined …

Cocktail Bitters

Angostura bitters originated in Venezuela in 1830, whilst Peychaud’s Bitters came from New Orleans at around the same time. They are essentially herbal tinctures (alcoholic extracts of herbs and spices). Despite their precise composition being a closely guarded secret, they both contain gentian, a distinctively bitter herb which I use in my clinic.
Today Angostura is primarily used for flavouring and colouring of cocktails – for example in pink gin.

Angostura and Peychaud’s Bitters originated in an era when ‘bitter tonics’ were a staple of Victorian apothecaries and sold as cures for a range of conditions from dyspepsia to nervous exhaustion.

One example of such a patent medicine was N. K. Brown’s iron and quinine bitters (shown above), which claimed to be “a thoroughly reliable tonic and health restorer [which] cannot fail to give tone and vigour to the whole system by purifying the blood, strengthening the bones, muscles and nerves and restoring in a wonderful degree the health and vigour of youth”
Clearly, those were the days of unbridled advertorial license, but behind the hype, we find elements of truth, as is so often the way when returning to long dismissed folklore: Iron does indeed contribute to healthy blood and bones, and quinine is effective in killing blood-born parasites such as malaria. So who knows? the two together may have been particularly effective. That said, an excess of either iron or quinine leads to its own problems.

By the mid 20th century, such ‘unsubstantiated’ health claims were banned and the era of patent medicine came to an end. Several, manufacturers survived by dropping the health claims and selling their products as foods (e.g. Bovril and coke), or, as in the case of Angostura Bitters as an alcoholic ‘non-beverage product’ – so called because it is not drunk neat (at nearly 45% alcohol that’s probably a good thing), but for flavouring of other drinks. Likewise, Indian tonic water still contains quinine, but now just for flavour, rather than as a prophylactic against malaria for which it was originally used.

As well as cocktail bitters like Angostura, many countries have their traditional alcoholic bitters such as Jägermeister (from Germany), which contains the extract of no less than 56 herbs and spices, and Campari (from Italy), which is made from an infusion of herbs and fruit including chinotto (from the bitter myrtle orange) and cascarilla (from the aromatic bark of Croton eluteriai).

Alcoholic bitters do exactly what they say on the tin – taste bitter – and it is the bitterness itself which has always been associated with the health benefits.

The role of Bitters

Whilst five tastes are now recognised (salty, sweet, bitter, sour, and umami), taste receptors in the mouth and upper digestive tract fall into just two categories: sweet and bitter, indicating an important role of bitter compounds in human evolution. It would seem obvious that detecting bitter tastes is primarily a defensive function to help us avoid ingesting toxins. But that does not explain why around the world people have traditionally revered bitter foods and drinks, whether that be the bitter melon of India, the gentian teas of Siberia, the bitter chicory and radicchio of Italy, or our modern obsession with coffee and chocolate.

Compared to most other animals humans have lost some bitter receptor genes and are generally less sensitive to detecting bitter flavours – an indication perhaps of our move away from eating raw and wild foods since the invention of cooking and farming. The usual explanation is that as humans selected, bred and cooked their food to make it less toxic and more palatable, we simply did not need that early warning system so much, and our bitter taste alarm system withered away like an unused organ. That only makes sense if you see bitter taste as solely indicating danger.

But what if bitter-tasting compounds are directly beneficial to us? Perhaps even essential? I have an alternative theory based on the beneficial hypothesis of bitters: As we domesticated our diets we increased the prevalence of sweet and bland foods. In doing so the option to avoid bitter flavours, which are intrinsically less palatable, would have increased. If bitters were essential for health (and we shall see below that this is increasingly becoming evident), then at some point this would have become disadvantageous. People who were less sensitive to bitter flavours would tend to consume more bitter foods than those who were more sensitive so there would have been selection pressure to evolve less sensitivity to these flavours thereby ensuring our continued intake.

In the last 50 years, however, with the industrialisation of the food chain, the development of artificial flavours and the widespread availability of sugar, we have had unprecedented access to sweet, bland (think ‘pasta’) and savoury flavours, whilst simultaneously there has been a reduction in bitter foods. These changes have coincided with a marked increase in diet-related disorders. The obesity epidemic is usually linked to an increased consumption of ‘obesogenic’ foods, but could the reduction of bitter food consumption also play a part? The answer seems to be probably, yes.

One way bitter flavours may play a direct part in obesity is via bitter taste receptors in the mouth which are directly connected by nerves to multiple brain regions, including the hypothalamus which hormonally regulates hunger and the digestive system. Via this route bitter flavours might exert a direct impact on nutrient intake and calorie balance. Indeed a 2013 study found that highly obese subjects pulled more disagreeable faces when sampling bitter flavours than did only mildly obese subjects, suggesting a sensory basis for their food choices. [Garcia-Burgos, 2013]

It also seems that bitter substances can reduce weight gain. A 2015 study found that quinine inhibited weight gain in mice fed an obesogenic diet. The bitter substance (quinine) appeared to prevent fat cells from multiplying. [Bert Avau, 2015] Furthermore, bitter treated mice had more brown fat activity, diverting energy into heat (thermogenesis) rather than fat stores.
Cultivating a taste for bitter foods may help you maintain a healthy weight. Interestingly, it might not be necessary to actually taste the bitterness on the tongue as the digestive tract has bitter receptors in many places along its length. In a recent study, scientists gave participants a sweet breakfast with hidden bitter compounds from gentian lutea (one of the herbs in Angostura Bitters) which were ‘micro-encapsulated’ so that they could not be tasted, but were released in the digestive tract.

Three hours later participants were allowed to eat as much lunch as they liked. Remarkably, those who unknowingly consumed the breakfast with the bitter compounds ate 30% fewer calories at lunch than those who did not have the bitter compounds [Mennella, 2016] Again, bitter compounds are associated with reduced energy intake.

Research on Gentian Root

Gentian – the bitter herb present in Angostura and Peychaud’s bitters, is a standard medicine used by Medical Herbalists like me. In fact, I have my own labelled product (photo above) which I prescribe for patients to help with digestive, liver and gallbladder problems, but its use extends well beyond the digestive system. In recent years Gentian root has been shown to have multiple physiological effects, which if given just a little advertorial licence would indeed read like the packaging of a patent medicine!

• Stimulates acid-, enzyme- and mucin-forming functions of the stomach [Olennikov, 2015]
• Improved bile flow [Oztürk N, 1998]
• Alleviating liver damage [Sheu, 2017]
• Liver protecting effects [Mihailović, 2014]
• Anti-coagulant activity [Cai, 2016]
• Anti-atherosclerosis effects by preventing endothelial inflammation [Kesavan, 2016]
• Anti-diabetic effects demonstrated in mice [Suh, 2015]
• Heart protection in Systemic Lupus Erythematosus [Huang, 2015]
• Vasodilation [Chericoni, 2003] and hypotensive [Uncini Manganelli, 2000]
• Anti-inflammatory effects [He YM, 2015]
• Anti-oxidant and DNA protective effects [Hudecová, 2012]
• Tumour inhibition in mice [Matsukawa, 2006]
• Anti-inflammatory in rheumatoid arthritis in rats [Yu,2004]

Bitter receptors all over the body

This image taken from a paper published in Nature (Bijal P. Trivedi, 2012) shows where taste receptors had been identified at that time: throughout the digestive tract. Most of these don’t produce a sensation of taste as they are not wired via nerves to the brain, but they are, nevertheless responding to the same compounds that are present in bitter tasting foods.

The presence of taste receptors in the gut made perfect sense. In fact, the discovery of sweet receptors in the intestine neatly explained a phenomenon that had mystified physiologists for more than 50 years: that eating glucose triggers significantly more insulin than injecting it directly into the bloodstream. At the time, however,  researchers struggled to explain the presence of taste receptors in the bile duct as food does not pass through this tract. What were they doing there?

Since that time, taste receptors have been identified all over the body, including in the testes, indicating that their function extends well beyond toxin detection.

As we explained in our post “The chemical warfare on your plate“, fruit and vegetables seem to exert health benefits via the process of hormesis. Rather than benefitting from the vitamin content of fruit and veg, it seems that our body responds to the presence of plant biological toxins – secondary plant metabolites – by up-regulating our own innate defences. What we are seeing with bitter taste receptors is a possible mechanism underlying part of this response.
One recent example in non-digestive tissue is the discovery of bitter receptors in lung tissue where they can induce relaxation and dilation of the airways. It is speculated they play a role in clearing infections and suggest potential novel treatments for asthma through the inhalation of bitter compounds. [Peta, 2016]

Collections of bitter receptors are also found on tiny finger-like projections called cilia on human airway epithelium cells. When the researchers stimulated the receptors using bitter compounds, such as nicotine or quinine, the cilia waved back and forth vigorously, helping to clear the airways of irritating compounds. (Bijal P. Trivedi, 2012)

A 2017 paper [Seo et al] explored the role of taste receptors found in neurones in the suppression of cancer activity in neuroblastoma cells. Activation of these bitter receptors was found to ‘.. inhibit the stemness, migration, and invasion of these cancer cells’. Although this paper did not directly look at the effects of bitter food components on cancer the authors point to previous studies in which

Bitter compounds and their agonists, including quinine, quinidine, chloroquine, and ally isothiocyanate induced apoptosis and suppressed cell proliferation in breast cancer and bladder cancer

The discovery and recent study of bitter receptors throughout the body is providing a mechanistic explanation for many of the folk-lore benefits claimed for bitter herbs. For example, willow bark is a herb with a long tradition. Recent studies have shown that a bitter compound it contains called salicin (a natural form of aspirin) inhibits cancer cells in a dish. The latest research has shown that this effect is mediated through the bitter taste receptors found in these cells.

Many bitter foods, it would seem, contain molecules that after digestion can bind to these tissue bitter receptors where they play an important signalling role. Indeed these bitter binding compounds…

… are involved in neurotransmitter function and in the regulation of neuronal and hormone signaling. Furthermore, impairment of this signaling… potentially contributes to central nervous system-related disorders, including Alzheimer’s disease, schizophrenia, and Parkinson’s. [Seo et al, 2017]

There are estimated to be thousands of bitter compounds and currently, over 680 have been studied along with their 25 human bitter receptors. Not all of these are from food sources, but we can expect more research on this fascinating topic in the coming years. [For the real nerds among you, see BitterDB, a database of bitter compound research]

Increasing bitter flavoured foods in the diet

In terms of putting this research into practice, there are plenty of bitter flavoured foods one can add to the diet beyond alcoholic bitters which prompted this post in the first place. A good starting place is to use more herbs and spices as these are one of the most concentrated sources of bitter principles. In our house, we try to keep a few pots of growing herbs on hand in the kitchen so it is easy to add them to any meal.

• Herbs and spices Add fresh dill, fennel, parsley or coriander leaves to salads, or seeds of poppy, coriander and celery to cooked vegetables. Curries and sauces allow concentrated doses of these ingredients in one meal. A village in Italy with large number of healthy centenarians place a lot of faith in rosemary which they use with most meals [The Telegraph, 5/9/16]
• Cruciferous vegetables are one source of a well studied bitter compound (sulforaphane) which is largely responsible for the health-giving properties of broccoli, cabbage, sprouts, kale and cauliflower.
• Salads are another opportunity, with plenty of bitter leaves available including chicory, rocket, watercress, lambs lettuce, oriental mustard greens, or mustard and cress. Dandelion leaves can also be used.
• Salad dressing can include bitter olive oil, mustard, herbs and lemon juice
• Beverages with bitter components include tea, coffee, cocoa, cocktail bitters, aperitifs, red wine, cider and beer.
• Wild and wild-like foods are often better sources of bitter principles than fruit and veg that has been selectively bred to be sweeter. These include berries – whose skins and pips contain most of the bitter components – crab apples, capers, walnuts, olives… the list goes on.

One word of warning. As bitter containing foods are often toxic at high dose, it is better to use a wide variety of bitter foods, rather than a large amount of a single kind.