Laying out the problem
Our recent post on bitters, left me with a lot of questions.
If bitter tastes indicate the presence of toxins and thereby help us avoid poisonous foods, why do they stimulate such positive physiological responses? Why would some of those responses protect us from metabolic diseases like diabetes and cancer? If bitter taste is merely a warning to avoid a particular food, then why do many traditions revere bitter foods? How do we explain why adults develop a taste for bitter foods that as children they found repulsive? Why does folk law say “Good medicine always tastes bitter”?
After a lot of pondering I think I’ve got an answer but to make sense of it I need to lay out what I see as the relevant parts of the puzzle first.
Read time: 16 minutes (3100 words)
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 …
Read time: 12 minutes (2300 words) Continue reading
Sleep and health: inflammation and ‘intestinal jet-lag’
The Mail (6th July) explains why ‘Too little and too much sleep is as damaging to your health’.
Dr Irwin concluded: ‘Together with diet and physical activity, sleep health represents a third component in the promotion of health-span.’
The importance of sleep is further flagged up in Gastroenterology & Endoscopy News (July 11th) in a detailed article discussing the growing body of evidence linking disruption of the body’s circadian clocks to changes in the gut lining and liver metabolism that contribute to inflammatory bowel disease (ulcerative colitis and Crohn’s) liver diseases and other gastro-intestinal ailments.
- See our post on Sleep And Health
Children who suck their thumbs and bite their nails suffer fewer allergies
The Telegraph (11th July) reports on a study that found that the protection afforded by thumb sucking and nail biting was life-long and present even where the child’s parents suffered from allergies. Prof Bob Hancox, the lead author of the study said the findings “suggest that being exposed to microbes as a child reduces your risk of developing allergies”. This is in line with observations that children brought up on farms or those with access to vegetable gardens have fewer allergies. Increased diversity of gut microbes is thought to be responsible.
Artificial sweeteners make you crave sugar
A great article in The Mail (12th July) explains why diet drinks may actually be contributing to overeating.
‘When sweetness versus energy is out of balance for a period of time, the brain re-calibrates and increases total calories consumed… The pathway we discovered is part of a conserved starvation response that actually makes nutritious food taste better when you are starving.’
We, like many others, have an instinctive distrust of the whole ‘artificial sweetener’ industry so it is great to find further science to back up our stance. Fans of the ‘just eat real food’ tendency will be right with us here I am sure.
Why fat isn’t the enemy but sugar and refined carbohydrates are
The Evening Standard (25th July) has a nice piece about cardiologist Dr Aseem Malhotra, who recommends a diet with more olive oil, full fat dairy, nuts and vegetables. However, in the comments section there is an interesting counterargument by another cardiologist Dr Khan that challenges Malhotra’s advice.
On careful reading though, I found less conflict than there first seemed. Both cardiologists agree that refined carbs and processed foods must go, but that fish, vegetables and olive oil are good. ‘Eat real foods’ is the undisputed starting point, again.
The areas of conflict seem to hinge on (1) the use of butter, and (2) meat v plant proteins (beans). Taking butter first: I think that butter is no problem once the rest of the diet is based around real food. However, if you are still eating lots of refined carbs, adding butter won’t magically make you healthier. With regards meat v beans, surely there is room for variety? My feeling is that the greater the diversity of real foods, the better. Which brings me to this piece:
The Mail (21st July) covers research that found a reduced risk of diabetes among people that ate a wider variety of foods. In particular: ‘people eating the widest variety of fruits and vegetables and dairy products also greatly reduced their risk of diabetes compared with people who had a less varied diet’
Another aspect of health appearing in both the Mail and Evening Standard articles is that both advise against jogging as a ‘healthy’ activity, recommending brisk walking instead.
Brisk walking, better than vigorous jogging
In the Evening Standard article Dr Malhotra says that orthopaedic surgeons are seeing people in their forties needing hip and knee replacements, and that no one should run on the pavement or treadmills. Meanwhile the Mail article reports on a new study by Duke Health, which has found that walking briskly on a regular basis improves pre-diabetes more effectively than intense treadmill exercise.
Recipes: Grain and sugar free biscuits, cakes, crackers and treats
So after you have taken that brisk walk, how can you start to replace your refined carbs with real whole foods?
‘Saying no to processed flour and grains doesn’t have to mean an end to the delicious homeliness of baking.’ says author Karen Thomson, in her article in The Mail (5th July) which has a great set of recipes along with advice on kicking the sugar habit.
I am looking forward to trying some of her great sounding recipes:
- RAW CHOCOLATE BALL POPS
- CHOCOLATE AND PEANUT PARADISE
- LIME AND POPPY SEED MUFFINS
- NUTTY PANCAKES
- PORTUGUESE CUSTARD TARTS
- NUT AND SEED LOAF
- PARMESAN CRISPS
- SEED CRACKERS
Fish, especially white fish like cod, is an excellent source of iodine – an essential developing brain nutrient – which, as we detailed in our Seafood talk, is critical during pregnancy. Unfortunately, Medical Express (26th May) reports on a study that found 74% of expectant mothers in the UK are not getting enough iodine, and 56% were unable to identify any iodine rich foods. Dr Emilie Combet, who led the research at the University of Glasgow, said:
“Iodine is crucial during pregnancy and the first months of life, to ensure adequate brain development, but achieving over 200ug a day of iodine through diet requires regular consumption of iodine-rich foods such as milk and sea fish.
The Guardian (20th July), meanwhile, encourages us to try a wider range of seafoods: “Little fish and shellfish have as much potential for a delicious dish as the overfished favourites”.
Helpfully, The Telegraph (26th July) provided a few good seafood recipes too.
In line with our assertion that seafood has been an essential part of human evolution and British traditions, the Eastbourne Herald (14th July) sheds light on the early Sussex diet. Multiple skeletons were excavated from an burial site near Eastbourne used between 600 and 700 AD “nearly all of them indicating signs of a diet high in seafood, which suggests that fishing was a big part of these people’s lifestyles” and that these people were “tall and well built”.
Chemical Warfare on Your Plate
Linked to one of our recent post in which we explained how counter-intuitively, the toxins in fruit and veg are responsible for many of their health benefits, comes this article in the Telegraph (30th July) explaining how modern fruit and vegetables are less nutritious because those very compounds are being bred out of them. All this points to eating more wild-like foods – for example, berries are closer to their wild cousins than apples and citrus fruits are, whilst rocket, watercress and lambs-lettuce make good close-to-wild salad choices.
Anxious Mice and the Microbiome
Following on from our murine musings last month, Medical Daily (29th July) report on a new mouse study which found that “Gut Bacteria Changes In Early Life Can Lead To Anxiety And Depression”. When the gut bacteria of depressed mice (!) was transferred to healthy mice they then become depressed.
The Mail Online (13th July) has a nice little story about the growing popularity of bone broth. Meanwhile, the Independent On Line (29th July) says that the popularity of cauliflower rice is growing. This easy low carb substitute for rice is a favourite of Jamie Oliver who is, they report, on a Paleo diet himself. If you are looking for further grain-substitution ideas, NBC’s Today (22nd July) provide “Caveman comfort food! 5 paleo recipes for popular dishes”
Sugar – the Public Health Battle Gets Going
I’m sure you won’t have missed all the news about sugar, with the UK government recommending daily intake is limited to 5% of calories from ‘free sugars’. BBC News (17th July) reported this as “Sugar intake ‘should be halved'”. The graph in their report (reproduced below), shows where the average Brit is now. For most, getting to 5% will require more than halving sugar intake.
This is one of the biggest public health drives in decades and appears to be on a collision course with many modern cultural norms. As the BBC health correspondent, Adam Brimelow, rightly points out the 5% target will be “a challenge for government, industry and the public”.
By way of example, The Telegraph (27th July) reports that when earlier this month industry giant Tesco announced that from September it would be removing sugary drinks aimed at children from it’s shelves, a public backlash began, with complaints flooding their twitter feed.
The BBC video accompanying this report suggests that to achieve these targets people will need to prepare and cook their own food from scratch. In a world dominated by takeaways and TV dinners this will be a major shock to Joe Public.
Although the government has ruled out taxing sugar, many leading bodies see it as a necessary step if education alone fails to change the situation. How it unfolds will be interesting. This debate is taken up in the Express (29th July) who report that a sugar tax could help the average Brit shed half a stone.
A key part of the sugar debate focuses on sugar sweetened drinks. NHS choices (22nd July) unpacks the Daily Mirror headline “Are sugary drinks causing 8,000 cases of diabetes every year?”
On the same theme, the Mail Online (29th Jul) reproduces an info-graphic that is doing the rounds this month, that explains – somewhat inaccurately – the effects on the body of drinking a can of regular coke. Click on the image below to view a full size version. (Also, see our info-graphic of the effects of sugary drinks on children’s livers)
Meanwhile on the other side of the pond, where the Union of Concerned Scientists point out that “Nearly three-quarters of packaged foods contain added sugar”, Fortune (29th July) reports that the FDA is coming under fire from industry simply for simply proposing that nutrition labels include the amount of ‘added sugar’! After all, ignorance is bliss, no?
- Why insecticides in your veg can be healthy (sometimes)
- SCOOP: The remarkable story of how wheat learned to turn an insect’s immune system against itself
- Why that might not be so great for us humans
Graphic by K Watson, USING original ‘killer vegetable’ cartoon by Ken Turner
Plants are in constant chemical warfare with the insects, microbes and animals that want to eat them. Unlike animals they cannot run away (although the angry sweetcorn dude in the image above suggests otherwise!) so their only option is to develop chemical deterrents. Consequently plants are chock-full of natural pesticides such as taninns, polyphenols, saponins, oxalates, cyanides, protease inhibitors, lectins and alkaloids to name just a few. Because predators eventually evolve tolerance to these toxins, plants are forced to continuously evolve new compounds to defeat them. So the chemical weapon development escalates.
According to new research, wheat may have developed a particularly clever chemical weapon in this insecticidal battle, and the extraordinary story of how it directly contributes to coeliac disease makes up the second half of this post. However, back to the story…
Most people don’t want pesticides sprayed on their foods, but they can’t avoid the natural pesticides found in the fruit and veggies they eat. Surprisingly, however, those endogenous plant toxins are not necessarily harmful. At normal doses many are harmless, and frequently beneficial – for example the sulphur containing compounds in broccoli, kale and cabbage appear to have anti-cancer properties. At higher doses though, plant insecticides may threaten health – for example the cyanide in almonds, especially bitter almonds, which can sometimes exceed safe limits as happened in the USA in 2014 leading to bags of healthy sounding ‘organic raw almonds’ being removed from the shelves due to their high cyanide content.
So how can these plant-made insecticides ever be good for us?
The answer: hormesis.
Hormesis can be summed up by the phrase a little of what is bad for you does you good. Hormesis works because the body reacts to low levels of toxins such as those found in plant foods by upregulating cellular detoxification and anti-oxidant pathways. One of the most significant of these pathways is the Nrf2 antioxidant ‘master switch’ (ref) which stimulates our own most powerful antioxidant glutathione.Upregulating our own antioxidants via hormesis appears much more effective than taking supplementary antioxidants. Over the last thirty years trials of antioxidant supplements have often lead to disappointing results, with either no effect or in some cases an increase in harm (e.g. see our post on vitamin A from animal sources). Many researchers, including nobel prize winning James Watson (co-discoverer of the structure of DNA) now believe that unless you are actually deficient, additional dietary or supplemental antioxidants actually promote disease.
Instead, scientists are increasingly ascribing many of the benefits of eating fruit and vegetables to the hormetic effect caused by their toxins rather than to their antioxidants.
“Hormesis is what makes fruit and vegetables healthy, not antioxidants”, Mattson Mattson & Calabrese, New Scientist 2008
The key to maximising the hormetic benefits from fruit and vegetables is to eat as wide a range as possible so that you do not get excess of any one toxin. The recommendation to eat a wide variety of different coloured fruit and vegetables comes from the idea that the different colours indicate different phytochemical compositions.
Studies of contemporary hunter-gatherers show that they eat many more plant species than their farming counterparts which may be one reason that they are invariably healthier. For example a recent study compared food systems and visual acuity across isolated Amazonian Kawymeno Waorani hunter-gatherers and neighboring Kichwa subsistence farmers. The hunter-gatherers consumed 130 food species (inc. 80 wild plants) whereas the farmers consumed only 63 species (and only 4 wild plants) and their eyesight declined faster with age.
So here’s a question: How many species do you consume? How many wild foods? The shocking answer for the world as a whole is provided to us by the United Nations:
The world has over 50 000 edible plants [yet] just 15 crop plants provide 90 percent of the world’s food energy intake, with three – rice, maize and wheat – making up two-thirds of this. United Nations, FAO
The role of agriculture
During the past 10,000 years of agriculture farmers have selected crops with high pest resistance. In some cases this has led to increased levels of certain plant toxins in the diet. High levels of gluten in wheat being an example.
Simultaneously, our preference for more palatable foods has led to the production of agricultural varieties that contain lower levels of bitter, sour or acrid compounds – for example modern salad lettuces are a lot less bitter than their wild counterparts, and apples are sweeter than their astringent crab-apple ancestors. This has reduced our exposure to the original diversity of plant compounds in the human diet.
Further changes caused by agriculture are due to selecting for high levels of sugars, starches and juiciness (water). The end result is a dilution of the phytochemicals in fruit and vegetables, requiring us to eat more of them, along with more simple sugars in the process, to gain the same quantity of plant micronutrients. A modern paleo diet, therefore, recommends eating berries – which are closer to their wild counterparts – rather than, say, apples and grapes, as they deliver more micro-nutrients per calorie consumed.
Furthermore, our reliance on a limited number of high yielding staple crops such as wheat and potatoes means that compared to our paleolithic forefathers we are exposed to a much lower diversity of phytonutrients, but much higher levels of the toxins and anti-nutrients they contain.
An example is the plant anti-nutrient phytate (phytic acid) which is found in its highest levels in cereal grains and nuts. It binds dietary iron, zinc, calcium and magnesium in the gut, reducing the quantities that can be absorbed. In developing countries where diets are limited with a high dependence on cereal grains phytate is a leading cause of mineral deficiency, especially in infants.
one third of world’s population suffers from anemia and zinc deficiency, particularly in developing countries. Phytic acid is known as a food inhibitor which chelates micronutrient and prevents it to be bioavailabe for… humans, because they lack enzyme phytase in their digestive tract – Gupta RK et al (2015)
In more affluent countries phytate is less problematic as the diet is more varied, but with grains typically making up 25% of the calories consumed in developed countries it still contributes to the risk of mineral deficiencies. For example last year a paper from the University of Texas examined how phytates in grains were responsible for zinc deficiency among US Mexican-American children, and US premenopausal women. On the other hand some possible positive effects of dietary phytates have been identified, including some anti-proliferative and anti-inflammatory actions. Small amounts in a varied diet, then, probably does some good and little harm.
Recently, a particularly interesting aspect of plant v insect chemical warfare has come to light as part of the explanation for coeliac disease. To my knowlegde, the remarkable story below has not been reported in the media or blogosphere before, so dear reader, you will be one of the first to hear of this research. Prepare to be amazed…
How a natural insecticide in gluten contributes to coeliac disease
Insects have a much simpler immune system than we do. They don’t have an adaptive immune system, relying on simpler innate immunity. However, they do have phagocytosis – the ability of certain cells to engulf microbes and then digest them inside the cell. But what do they do if the foreign particle is too large for phagocytosis? Below are mosquito larvae showing how they cope:
If an insect is invaded by a foreign particle too large for phagocytosis – a parasite or splinter for example – it will encapsulate it instead. This process requires immune cells called haemocytes to form a pallisade (fence) around the invading foreign body, thus immobilising it. The initial cells that bind this foreign body are broken down as further cells rapidly grow extensive sheets to wall off the invader, effectively locking it away in a cage from which it cannot escape. This is what has happened to the nemetodes inside the bodies of the mosquito larvae above. Cells then release glue-like glycose amino glycans (GAGs) which create a tangled water-holding matrix that prevents nutrients reaching the ensnared parasite. It’s an effective strategy for these lavae, but what has this got to do with gluten?
A recent study by Prof Simon Murch’s team at the University of Warwick investigated one aspect of the mechanism of intestinal damage (villous atrophy) in coeliac disease. They were interested in the way that the lower layer – the lamina propria – increases in thickness as the lining of the intestine becomes damaged. What they found was a direct link to insect encapsulation processes.
Perhaps the reason their paper didn’t get picked up by the press is the title: Matrix Expansion and Syncytial Aggregation of Syndecan-1+ Cells Underpin Villous Atrophy in Coeliac Disease. It doesn’t sound very promising does it? Yet it explores a fascinating hypothesis that brings together many of the threads I have been working up to in this post. I will attempt to elaborate below…
First, a bit of background:
Villi are microscopic projections covering the inside of the small intestine, providing a huge surface area essential for absorption of nutrients. (Upper image: biopsy showing healthy villi)
In coeliac disease the villi are eroded, leaving sections of the intestine that are flat and unable to absorb nutrients. (Lower image: coeliac biopsy showing villous atrophy) How gluten can cause these changes in the small intestine is currently the subject of intensive research efforts.
One little appreciated fact in this process is that the damage to the villi is bottom up, not top down. If you look carefully you can see that the lower layers of cells (the lamia propria) has actually expanded upwards, increased in thickness, and destroyed the structure of the villi above.
Prof Murch’s team investigated the mechanism of this cell overgrowth in the lamia propria. What they found is that it shares many biological features with insect encapsulation.
We hypothesise that our findings, of syndecan-1+ cell syncytial aggregation with excess GAG production, recapitulate core elements of the invertebrate encapsulation reaction, in which insect haemocytes form palisades around an invading pathogen or object too large to phagocytose
Recruited cells are characterised by syndecan expression, required for invertebrate haemocyte binding to laminin and cell cluster formation. Our findings in coeliac mucosa show a similar palisading of syndecan-expressing leukocytes to form syncytial aggregates, together with a lysis of a proportion of these cells, with loss of their plasma membrane. Sulphated GAG including HSPG accumulated around these aggregates in an expansion of the lamina propria.
In insects, the GAG production and matrix expansion is limited by a subsequent melanisation reaction dependent on the enzyme prophenoloxidase, in which haemocyte responses are downregulated by α-melanocyte stimulating hormone (α-MSH). In coeliac mucosa the gliadin-induced IL-6 response is similarly attenuated by α-MSH.
The release of GAGs during insect encapsulation, remember, prevents nutrients reaching the parasite. In the lamina propria the GAGs will similarly reduce nutrient uptake – a double whammy for the coeliac intestine – villous atrophy reduces surface area for absorption, then excess GAGs reduce it further!
Another similarity in both insect encapsulation and coeliac disease development is the stimulation of tissue transglutaminase (tTG), which is an enzyme that causes gluing together of tissues. tTG is a major player in coeliac disease as in the presence of gliadin it can become the target of autoimmunity. (The primary coeliac blood test is for tTG antibodies).
This is all fascinating and points to an evolutionarily conserved mechanism shared by both invertebrates and mammals. However, it begs the question – Why would gluten stimulate a response in the human intestine that is equivalent to what insects do when they are invaded by parasites? The answer to that question is where the true awesomeness of this story lies…
Gluten as a wheat-made insecticide
It is notable that wheat grain has very few insect pests – a fact that made it a good crop to domesticate ten thousand years ago.
A clue as to why this may be is that the few insect species that are able to predate it have all evolved enzymes that can break down gluten. Gluten is very resistant to normal digestive enzymes. That is why many gluten proteins reach the human intestine relatively intact – and why it can set off an immune reaction.
It is notable in this context that the glutenin moiety of wheats provides an effective barrier to predation by most insect species, and there are notably few successful phytophagous predators. Insects able to predate wheat share a common ability to predigest gluten with salivary enzymes, which has evolved separately in species from the northern and southern hemispheres.
The final piece of this story is how gluten pulls off this trick. It appears that the insect immune response to parasites involves the release of two proteins during the early stages of encapsulation. These have been found to have uncanny similarities to some proteins in gluten. The implication is that wheat may have evolved these gluten proteins as an effective insecticide strategy that works by over-stimulating the insect’s own defense system by triggering the encapsulation process inappropriately and presumably fatally! In humans a similar inappropriate triggering is caused by gluten ingestion that can lead to the destruction of the small intestinal villi, via a process which is extremely similar to insect encapsulation.
Cool or what?
Hats off to Prof Murch’s team!