Chapter 6: Should we change places, diets or genes?

By Dagmar
In Interesting stuff
Apr 20th, 2015

– Dealing with migration headaches

This is the continuation based on the sixth chapter of an excellent book written by Gary Paul Nabhan: Why some like it hot.

The chapter starts with highlighting that since people have evolved on a certain diet and within a certain environment, we can observe the changes in our physiology after we move from our traditional environment to another. Until then there was almost a perfect balance or ‘a sync’  and overall health, making the specific population within a specific culture/environment the fittest. However, because we are adaptable living creatures, every such challenge triggers a response and since we are all unique, we respond differently: some adapt better or more easily to the new conditions, others less so.

However, it would be quite simple if it was only our genes determining our response to the challenge. It is more complicated than that. Our grandparents were exposed to a certain cocktail of natural chemicals, often poisons, such as toxins in tapioca or some herbs they used in cooking. They have learned how to eliminate the negative effect or the actual presence of these substances and they thrived. These practices are varying from continent to continent and from region to region. For example, we normally perceive as disgusting to spit into the manioc root pulp among African and Latin American cultures, which have been using this method to deactivate bitter substances in the manioc. When leaving this mass for long enough, it becomes tasting sweet. They basically detoxified otherwise a poisonous food, making it palatable and nutritious. We will probably never find out how they came to this practice, but it is for sure that it works. Many ethnics have their unique methods of detoxification of food or making it more nutritious by either adding something or processing it the way so that the anti-nutrient properties are deleted.

Moving to a different environment represents an exposure to a different cocktail of these natural chemicals, which also interact with our biochemistry and expression of our genes. This means we have had those genes, but they did not express, or vice versa: we had them expressed but under new circumstances their expression becomes inhibited which makes them dormant, hence affecting our metabolism in a positive or negative way. New culture and behaviour also affect this relationship as they are often intermingled: new culture brings new meals, new ingredients and cooking methods and different pattern of eating…

The chapter continues with the description of the customs of Navajo tribe. They lived in their land for over 15 centuries but before that they moved frequently from one habitat to another, exposing themselves to new environmental stimuli every now and then. Gary talks through a story when ‘rather simple nutritional interventions have reduced health risks that  the Navajo might otherwise have experienced in their newfound lands’.

Gary says:

it is also a story that hints at why new gene therapies might not necessarily be the best answers to the particular challenges that these people face in their more recently adopted homes.

He talks about over 70 years old Navajo medicine man called Mitchell, with whom he had a discussion about different approaches to raising the herd of sheep during and after the droughts. While the modern approach was to feed the sheep expensive timothy hay, the Navajo would escort their herd to a higher altitude where the sheep would not only munch on juicy grass but also a sage bush. This would give their meat a typical sage flavour, meaning that Navajo would not need to spice up the meat when roasting. Gary added his own clan tradition from the border between Lebanon and Syria. Their land thrives with wild thyme so their sheep also has thyme flavour when cooked. Navajos use sage as a versatile herb. They also chew it raw. They virtually find a use for the whole plant, including the roots and pollen. Mitchell created a booklet for children where he shared his knowledge of plants so the tradition can be maintained. This was done with collaboration with a school in Chinle so that children can learn their traditions at school. It is a precious knowledge and it would be a pity if it got lost.

The Navajo divide the plants in four main groups:

  1. food
  2. medicines
  3. unknown effect
  4. poison

Gary wondered whether one can get overdosed with a plant that is considered a food and Mitchell confirmed that it is often the case when people go on the flea market and buy herb for cooking just to end up in a hospital because they used it inappropriately. They should consult the use of the plant with somebody who knows it and its uses before they attempt to experiment on themselves.

The medicine man will apply the medicine in a context. Instead of giving a dose to a patient, he will consider the way of preparation of the medicine, how much of it will be given and when and to whom it is going to be given. All these aspects are important because it matters in what context and what amount the active substances found in sage (coumarins) are given. Then, there are different species of sage. Some are less favourable as medicines because they were found to stimulate growth of some tumors. Other species are used as narcotics, they are also able to eliminate intestinal parasites or manage blood clotting.

Gary mentioned one interesting thing:

If these foods and medicines were not anciently used but new to humankind, and the Food and Drug Administration had to determine whether they were safe enough to put on the market, I doubt whether the agency would approve them. The reason is they can trigger so many deleterious as well as beneficial effects in human metabolism.

About a ‘quarter of the native foods and medicines of Navajo people contain coumarins’. However, these compounds are not limited to the South America and a single tribe. Many every day foods contain these active substances, including coriander, cherries, plums, oranges and figs or even parsnips and chickpeas. So, what is the problem when the coumarins are so widely present in our food already? What is so interesting about them in connection to Navajo?

When otherwise innocent herb becomes a poison

Navajo have been found to be polymorphic (carrying more than one variant) of a gene coding for serum albumin A. This is a water soluble protein found in our blood that helps carrying other water insoluble compounds such as steroid hormones. It also binds to coumarins and warfarin (a drug derived from coumarins) to control blood clotting. In fact, about half of our blood proteins is comprised by albumin. A mutated form of albumin present in Navajo and few other ethnics in the world make them particularly sensitive to the action of coumarins or warfarin. Homozygous people who are having only one form of a healthy gene respond appropriately to the specific amount of drug, but those with two different alleles or both affected ones, such as Navajo, would risk a hemorrhage because this drug will become more potent in their system. Some portion of their albumin is simply not binding the drug efficiently.

Further in the chapter you can read about the migration of Navajo ancestors from Asia, with which the other tribes on the American continent seem to be related and where they might have picked this different form of gene. So here occurs a dual effect:

  1. the Navajo finally ended up in South America which is abundant in coumarin rich plants potent for various physiologic effects mentioned earlier,
  2. their acquired higher susceptibility to these coumarins based on their genetic profile. This is similar to the favism I referred to in one of the earlier chapters.

The example with the albumin variant is not a single case. There are other genetic mutations that make people react more or less strongly to the coumarins or any other compounds found freely in the nature. Gary mentioned factor IX which some of us are also having and which makes the affected people more sensitive to coumarins and warfarin, similarly as for the albumin heterogeneity. The resultant disease of having this factor is haemophilia B. Giving such a potent drug for thinning blood to a haemophiliac could result in death. On the opposite side of the scale are people carrying a gene that makes them particularly well tolerating the warfarin or coumarins to the point that they seem to be unresponsive to the treatment.

All in all, there are some sixty variations on this theme. That is, there are sixty different CYP genes in the P450 family. Many of these allelic variants can strongly influence how we metabolize some thirty prescribed and over-the-counter drugs, as well as countless foods and environmental chemicals.

Gene therapy: opening a Pandorra box?

Earlier in this chapter I mentioned that it may not be the best practice trying to fix the genes that makes us unique and more or less responsive to certain environmental stimuli, including the coumarins. Gary describes a possible near future of gene therapy how an individual will have a chance to have the ‘incorrect’ genes or gene expression fixed via the specifically designed virus or any other way even before the birth. While this may seem to be positive, bearing in mind the dual action of these compounds (serving bad but also a good purpose), the individual may lose its responsiveness against the good effect of these compounds which could otherwise help him cure the cancer, get rid of the intestinal parasites, win over nicotine addiction or treat extensive blood clotting. In other words:

Thus, a hypothetical gene therapy could eliminate a health risk and paradoxically negate certain health benefits at the same time.

This, however, does not mean that gene therapy has no future. It will need a careful evaluation whether its use will be more to the patient’s benefit or harm. If in doubt, there are other ways how to win over the nutrient-gene interaction.

Gary mentions the nutritional intervention for reducing the risk for heart attack due to clogged arteries. There are people who are genetically prone to highly elevated amino acid homocysteine, which is a result of the animal protein breakdown. It also may increase the risk of cancer and some other degenerative chronic diseases. One in ten men and one in twelve women may die from heart disease as a consequence of high homocysteine levels in their blood, regardless of the type of fat they consume. These people develop a premature atherosclerosis, i.e. earlier than the average population. Again, it was found that individuals having both recessive alleles coding for a defective gene responsible for the metabolism of folic acid (vitamin B9) were at risk of ‘homocystinuria’, high concentrations of homocysteine in their blood. These individuals are simply deficient in a particular enzyme methylene tetrahydrofolate reductase (MTHFR) which is needed for conversion of homocysteine into methionine, another amino acid important for our health. People having both recessive alleles have a three times increased risk of developing premature atherosclerosis than those that have one or both alleles dominant. The dominant allele puts the recessive one to a shadow and does not allow it to express fully or at all. Those having both recessive alleles do not have this protection so their protein is malfunctioning or not active at all.

However, the fate of these affected people is not sealed! It was found that increased consumption of folic acid could keep the premature onset of atherosclerosis at bay. What is more, this treatment was found to be successful ONLY in those homozygous recessive carriers. Can therefore the supplementation of the whole population with folic acid help?

Gary says that in the past it was calculated that it was more cost-effective to rather screen and treat the affected individuals than delivering this supplementation to every person in the country – until there was found the link between folate deficiency and spina bifida. That was a game changer and now certain foods are fortified nationwide with added folate. This helped to increase the folate intake without additional supplementation among the majority of the population, helping to decrease occurrence of some diseases related to the folate deficiency. The result was a lower incidence of spina bifida among the newborns and also reduced the number of cardiovascular diseases by up to 50 000 per year in the U.S. Gary says that this was an example how the expensive gene therapy is not necessary in comparison to a relatively cheap nutrition intervention regarding to the gene-nutrient interactions. The initial calculation which showed the supplementation as more expensive looked different when other diseases were prevented, changing the balance of the book.

Instead of treating humans why not treating plants?

Some scientists proposed an idea to create breeds of grains that would produce higher amounts of folate so it would not need to be added to the food items – making this method more cost-effective in comparison to fortification which is practiced today.

“Why mess with people’s genes … if we can more expendiently tinker with the genes of foods in ways that can make up for our genetic vulnerabilities?”

While grains are a poor source of folate, green and leafy vegetables are naturally rich in it. These scientists proposed that it is feasible to insert a gene from green plants to grains or to manipulate its genome so it will keep more folate in the grain instead of only in its leafy part. My question is: why not eating more greens instead? Do we really need to manipulate with genomes of the grains?

I am not alone with this view. Bill McKibben (cited in the actual chapter) said:

“What you need is not miracles from Monsanto; what you need is a diet rich in local greens!”

McKibben also foresees that if we have maintained a high consumption of fresh greens there would be no need for manipulating with the genes of food crops or even our own genes.

I am adding: this has been effective for millennia when people consumed their natural diet, long time before we started cultivating grains which became our staple. It is only a recent misfortune that we have forgotten the right way of eating which we are trying to fix with messing up with the genes.

Gary continues towards the end of his chapter that the season for growing fresh greens is particularly short in northern latitudes. This represents additional challenge to the Scandinavians, Greenlanders, Scotch, Danish and other population, depending on animal sourced food during dark months.

“Protein – and fat-rich meats, while nutritious, elevate homocysteine levels and increase the risk of heart disease and cancer.”

says Gary and adds that this was especially the case for the MTHFR enzyme deficient people of the North whose only cure or prevention would be a frequent intake of greens to lower their homocysteine levels.

A bit in contrary to this I would suggest that consumption of organ meat, such as liver, could provide quite a lot of folate and also B12 vitamin. But then there comes additional story which points at Inuits who consume lichen which they call ‘stomach salads’. These greens are not only rich in folate but also other vitamins, minerals and fibre, of which the Inuits have very little in their animal based diet, including the liver and other organ meats. The lichens contain other protective plant compounds which cannot be found in meat and they help in maintaining immune system via various plant derived antioxidants.

Geography matters

One important thing is that the geographical position of the tribe or civilization was determining the frequency of the enzyme deficiency among that society. Those in northern latitudes were less likely to survive with a higher incidence of atherosclerosis at younger age if their diet was not rich in greens due to a natural selection. However, this makes me expect that the gene can be found more frequently in Mediterranean and tropical latitudes, where greens are consumed all year long and protecting the recessive allele carriers which then can give their affected genes further to their offspring without major consequences. Despite this Gary wrote that “the genes that elevate homocysteine are far less frequent”  among warm latitudes but I think he meant otherwise. I let the reader, who might know more, to correct either me or Gary.

Gary continues with his observation from the British Isles where people rarely serve fresh greens in pubs, mirroring the actual eating habits of the population. The cuisine was predominantly comprised of animal resources and fat and flour laden meals which puzzled Gary how on earth could the society survive on this kind of diet for the past centuries? The answer came from his British friend as a surprise: many Britons spend the rest of their adult life as expats in countries where they can eat enough fresh and green produce together with the domestic people.

It was a joke, of course. But no other explanation was offered in the book.

Instead, I would suggest the prevalence of the genes, the opposite one to what Gary proposed earlier, is more probable: less frequent among Britons and other northern cultures due to natural selection and perhaps they have some source of folate from the animal organ meat. Steak and kidney pie, anyone? Or the liver pate could also supply some folate because liver is quite a nutritious piece of ‘meat’. Only the pregnant women should be cautious due to a possible vitamin A overdose, having a serious effect on the foetus. Gary, who did not mention these details, found the survival rate of Britons on such un-fresh diet as a paradox. I do not see it this way. It would be worth of further discussion.




Chapter 1: Discerning the histories encoded in our bodies

Chapter 2: Searching for the ancestral diet

Chapter 3: Finding a bean for your genes and a buffer against malaria

Chapter 4: The shaping and shipping away of Mediterranean cuisines

Chapter 5: Discovering why some (don’t) like it hot

Chapter 6: Should we change places, diets or genes?

Chapter 7: Rooting out the causes of disease

About "" Has 48 Posts

Graduated at London Metropolitan University: BSc (Hons) Human Nutrition in 2014. Working as a research assistant at the MRC, The University of Cambridge.

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