Today I have the pleasure of sharing a very special interview with you. The interview is special for a number of reasons. First of all, it’s very comprehensive. It’s by far the longest and most detailed interview that has ever been published on Darwinian-Medicine.com. Second, much of my work here on the site revolves around the topics that are covered in this interview. You’d be hard-pressed to find an article here on Darwinian-Medicine.com that has no relation whatsoever to the things Pedro Carrera Bastos (the interview subject) and I talk about in this interview.
Third, Bastos is a part of the distinguished group of scientists who’ve spearheaded the research on evolutionary nutrition and health. Fourth, Bastos is one of the lead authors of what is arguably the greatest review paper on health and medicine that has ever been published. The paper I’m talking about is entitled The western diet and lifestyle and diseases of civilization and was published by Dove Medical Press in 2011. If you haven’t already read that paper, I highly recommend that you do so; particularly if you find the information contained within this interview intriguing.
What can we learn about nutrition and health from traditional people who live under conditions that resemble the conditions under which our preagricultural ancestors lived?
In the aforementioned paper, Bastos, in collaboration with other prominent evolutionary thinkers, summarize the findings of explorers and researchers who’ve examined the health and physical fitness condition of non-westernized, traditional people, which they use, in combination with other types of data, to create a Darwinian prescription for the diseases of civilization. Besides writing that great article, Bastos has been a part of various other interesting scientific projects that have to do with Darwinian medicine and evolutionary health.
In the following exclusive and comprehensive Interview, which I conducted quite recently, he talks about this work and shares his thoughts on nutrition, health, and the changes that Darwinian medicine can bring to our conventional medical system. I’d argue that it’s a must-read for anyone who’s genuinely interested in evolutionary health and medicine.
I hope you enjoy it and learn a thing or two.
1. Please tell us a little about yourself. As I understand it, you’re currently enrolled at the PhD program at Lund University. What did you do prior to starting your PhD? Where did you get your bachelor’s and master’s degrees and which subjects did you study? What do you do besides working on your PhD?
Thank you very much for the opportunity to do this interview.
I am Portuguese with Spanish origins (from my mother’s side) and I am 42-years old. My background and professional pathway is far from linear. I actually started by obtaining (in 1999) a Bachelor of Arts (5 year-degree) in Economics and Business Administration. This led me to work for the Portuguese state performing various economy and finance-related tasks for almost 10 years.
When I began exercising at a local gym in college, I got hooked on exercise science, an interest that was fueled by my trainer at the time (and now good friend) Miguel Otero, who was a real exercise science geek with a lot of knowledge. He always explained every exercise from a biomechanical perspective and gave me lots of material to read. This, coupled with my old school interest in biology, made me pursue education in exercise and health, which gave me the opportunity to have a part-time night job (along with my day job as a public servant) at a health club, where I worked as a personal trainer for 3 years. During that period, I discovered nutrition and it was love at first sight. I then went on a path of self-experimentation, where I managed to solve or greatly improve health issues I had experienced for most of my life (gastrointestinal problems, rhinitis and sinusitis) with dietary changes. This changed my vision about health care. During that time, where I was obsessively reading everything I could find on nutrition, I stumbled upon Dr. Michael Colgan’s books, which made me realize that nutrition is a highly complex and fascinating discipline. He was my first inspiration to pursue a career in nutrition.
Another person who also inspired me greatly, in those first years, was Custódio César (a well-known nutritionist in Portugal, who over the years became one of my best friends). He motivated me and helped me pursue a career in nutrition. So, and to cut a long story short, I left my job as a personal trainer in 2005 and decided to start studying nutrition, obtaining a BS and MS in Human Nutrition (in Spain) and post-graduate diplomas in Clinical Nutrition (in Portugal) and doing various courses in biochemistry, molecular biology, immunology, and pathophysiology.
But the game changer happened when I read Professor Loren Cordain’s scientific paper Origins and evolution of the Western diet: health implications for the 21st century. Thinking from an evolutionary perspective shaped my mind and gave me a new obsession. I started reading all the papers and books I could find on evolutionary medicine and in 2007 I went to London to finally meet Dr. Cordain at a conference where he was speaking. We became friends, and I have now worked with him for a number of years writing articles for his website and collaborating on a few papers. I will forever be grateful to Loren. He taught me a lot about evolutionary medicine and nutrition in general, opened many doors and introduced me (directly and indirectly) to various players in this field, such as Dr. Boyd Eaton (one of the fathers of evolutionary nutrition), Maelán Fontes from Spain (a current research colleague and close friend), Alejandro Lucia (a Professor and a top researcher in exercise physiology from Spain, with whom I am collaborating), Ben Balzer from Australia (a physician and one of the best minds in evolutionary medicine), Robb Wolf from the US (a biochemist and the best “biohackers I know”), Óscar Picazo and Fernando Mata from Spain (close friends who are working with me at NutriScience), David Furman from Argentina (a top immunologist and expert in chronic inflammation working at Stanford University, with whom I am collaborating), Stephan Guyenet from the US (one of my main references in the obesity field), Lynda Frassetto and Anthony Sebastian (both nephrologists at the University of California San Francisco and experts in acid-base balance), Michael Crawford from the UK (a world renowned expert in DHA and Director of the Institute of Brain Chemistry and Human Nutrition, at the Imperial College London), Marcelo Rogero (a great researcher and Professor of Nutrigenomics at the University of Sao Paulo, Brazil), Sérgio Veloso (a cell biologist from Portugal currently working with me, who has one of the best health blogs I know), Filomena Trindade (a Portuguese physician based in the US who is an expert in functional medicine), Remko Kuipers and Martine Luxwolda (both physicians from the Netherlands, who conducted field research on traditional populations in Tanzania), Gabriel de Carvalho (a pharmacist and renowned nutritionist from Brazil), Alex Vasquez (a physician from the US, who is an expert in functional medicine and Rheumatology), Bodo Melnik (a Professor of Dermatology and expert in Molecular Biology from Germany, with whom I have published papers on milk and mTOR signaling), Johan Frostegård from Sweden (a rheumatologist and Professor at Karolinska Institutet, who has been a pioneer on establishing the role of the immune system in cardiovascular disease), Frits Muskiet (a biochemist and Professor of Pathophysiology from the Netherlands, who, thanks to his incredible encyclopedic knowledge and open-mind, continuously teaches me more than I could imagine and who I consider a mentor), and the Swedish researchers Staffan Lindeberg, Tommy Jönsson and Yvonne Granfeldt, who became close friends and mentors.
In 2010, Staffan invited me and Maelán Fontes to collaborate with his group, and in 2014 we both enrolled in a PhD program at Lund University, under his supervision, with Tommy Jönsson, Yvonne Granfeldt and Kristina Sundquist as co-supervisors. Sadly, Staffan passed away about a year ago and this affected me deeply. To me he was not only a wise and highly intelligent professor and supervisor, but above all a mentor, a great friend (Staffan, and his wife Eva, always treated me like family) and an example of humility, integrity, tolerance and kindness (even in the face of adversity), who continues to inspire me.
But let’s change the subject or I will get overly emotional. You asked what I do besides working on the PhD (which is focused on zonulin, inflammation and cardiometabolic risk factors and hopefully will be completed in a year or so). In terms of research, I not only collaborate with Lund University, but also with Professor Alejandro Lucia (from Europea University of Madrid in Spain), and Dr. David Furman (from Stanford University, USA) on a few research projects and scientific publications. But most of my time is dedicated to lecturing and to NutriScience, an education and consulting company I started in Portugal, in 2009 (when I left my job as public servant) with two friends (André Matias and Alexandre Azevedo, both nutritionists). We organize on-site and online advanced nutrition courses, seminars and conferences for health professionals and we have recently expanded to Spain and Latin America (thanks to my good friends Fernando Mata and Óscar Picazo, who are the real driving forces in those countries). Finally, I have been very fortunate to be frequently invited to speak for researchers, nutritionists, physicians, and other health professionals in Europe, Latin America, the US, Asia and New Zealand, which has been an amazing experience and has allowed me to meet and become friends with many great scholars, researchers and clinicians. I have to say I never imagined that one day I would be doing what I am doing and sometimes I have to pinch myself to realize this is real.
2. A lot of your research revolves around evolutionary nutrition/medicine-related topics. How did you get interested in Darwinian/evolutionary medicine, and why did you decide to pursue a career within that field?
The problem with nutrition, in my view, lies in the fact that most of the evidence comes from either observational studies, which cannot demonstrate causality (even a systematic review of observational studies isn’t able to show cause and effect) or from short-term clinical trials often with small sample sizes and/or with significant methodological limitations or bias. When I was introduced to Boyd Eaton, Loren Cordain, Staffan Lindeberg, and Tommy Jönsson’s work, I finally found a template to make sense of those often-conflicting studies. Without the evolutionary approach their work and the work of others (such as Frits Muskiet, Remko Kuipers, Michael Crawford and Rainer Straub) has provided me with, I would feel completely lost in this turbulent sea of information.
3. It’s widely known within the evolutionary health community that traditional, non-westernized people (e.g., hunter-gatherers) are a lot healthier than westernized people, in the sense that they are lean and largely free of chronic disease. Could you provide a little more detail as to exactly how the typical hunter-gatherer or traditional Kitavan differs, health and fitness wise, from the typical American? What’s the difference with respect to blood glucose levels, insulin sensitivity, blood lipid profile, blood pressure, and so forth?
Indeed, there are data showing hunter-gatherers, horticulturalists, and other populations minimally affected by modern habits exhibit superior body composition, physical fitness, and health markers compared to typical “healthy” citizens of industrialized nations.
Let us look at a few examples:
- Lower body mass index in hunter-gatherers (e.g. Australian aborigines, African pygmies, !Kung of Southern Africa, Kreen-Akrore of Brazil, Greenland Inuit and Yanomami of the Northern Amazon rainforest on the border between Venezuela and Brazil), horticulturalists (such as the Tsimané in Bolivia, and various indigenous populations of Papua New Guinea), and traditional pastoralists (such as the Maasai from Tanzania and Kenya and the Evenki from Siberia) compared to control populations from industrialized countries.
- Lower tricipital skinfold (mm) in the Congo pygmies, the San people of the Kalahari desert, the Hadza of Tanzania, the Australian aborigines, the Tukisenta and Lufa horticulturalists of Papua Nueva Guinea, the Biak of West Papua (Indonesia), the Solomon islands’ natives, the Ainu people of Japan, the traditional Quechua farmers of Peru, the Venezuelan Warao, the Tiriyó people inhabiting the border between Suriname and Brazil, the Mexican Tarahumara farmers, and the Igloolik Inuit in Northern Canada (before acculturation), compared to young healthy westerners.
- Persisting high insulin sensitivity among middle-aged and older individuals in non-westernized traditional populations at a time when they still maintained their ancestral lifestyle, such as the African pygmies, the Ainu people of Japan, rural communities in Papua New Guinea, and traditional Pacific Islanders.
- Very low prevalence of type II diabetes in Pacific islanders who retain their traditional lifestyle, unacculturated tribes of Brazil, the Tsimané of Bolivia, the Shuar hunter-gatherers of the Ecuadorian Amazon, and the Kuna of Panama.
- Much lower prevalence of hypertension in indigenous populations of Papua New Guinea and South Pacific islands before modernization, the Yi farmers of China, unacculturated tribes of Kenya, the San people, the Hadza, the Pygmies of Congo, the Kuna, the Tsimané, the Yanomami, and various Amerindians of Brazil, compared to sex and age-matched populations from industrialized countries.
- Greater maximum oxygen consumption (VO2 max) in the Lufas, Maasai, !Kung, Warao, Eskimos and the Sami people of Lapland, compared to average Americans.
- Better visual acuity in North American Indians and Eskimos of Greenland (before acculturation), hunter-gatherer tribes of Gabon, populations from rural Malawi, the Sherpa of Nepal living in rural areas, and traditional indigenous people of Vanuatu, compared to industrialized populations.
- Lower bone fracture rates, compared to western populations, in rural Melanesians, the Maori of New Zealand who retain a traditional lifestyle, rural populations from Nigeria, and traditional Bantu populations of Zimbabwe and South Africa, despite a lower calcium intake in most cases, and an equivalent or even lower bone mineral density.
4. Your late mentor, Staffan Lindeberg, was in charge of conducting the Kitava study, which documented the superb health of the traditional Kitavan population. The study, which is arguably one of the greatest studies on evolutionary nutrition/health that has ever been published, went on to become famous within evolutionary health circles. Is there anything about the Kitava study that you feel deserves more attention? Perhaps something that even most people who are familiar with the Dr. Lindeberg’s research don’t know…?
Indeed, the Kitava study has become quite famous among evolutionary medicine enthusiasts. However, it is virtually unknown to many biomedical researchers, which is strange and sad, since this study offers various clues to better understand the causes of many non-communicable diseases, also called western diseases, such as type II diabetes and cardiovascular disease. As so, I would like to give your audience an overview of this remarkable study in the hope that more people get interested in exploring Staffan’s Kitava data.
Kitava is a small island (25 km2) belonging to the Trobriand archipelago, off the east coast of Papua New Guinea. In 1990, it had a population of 2,250 individuals (of which 1816 were estimated to be older than 3 years) living as traditional horticulturalists in villages or hamlets, each containing 20 to 400 persons. No electricity, telephones or motor vehicles (except 1 motor boat, which was rarely used) were available, and except for clothing, tools, smoking, kerosene lamps, morals, religious beliefs, certain customs (such as soccer and education) and some sanitation, there was minimal western influence.
Staffan and his family (wife and young daughters) spent 7 weeks (between November and December of 1990) on the island, staying with a local family, and eating and living like Kitavans. During this period, he collected blood and hair samples, carefully observed the dietary habits of various natives, conducted semi-structured interviews, as well as blood pressure measurements, and anthropometric evaluations, and recorded resting electrocardiograms (with the help of a portable EGC, an old Mac and a petrol generator that provided electricity). And what did he find…?
Kitavans had a daily physical activity level comparable to a farmer or construction worker and ate a traditional diet with negligible amounts of western foods. The diet was composed mainly of fish (100-300 g per person 3-4 times a week), tubers (yam, sweet potato, taro, and yucca, totaling 1,2 kg per day), coconut (~100 g per day), fruits (banana, papaya, pineapple, mango, guava, and watermelon, amounting to a total of approximately 400 g per day), and other plant foods (leaves, okari, which is a nut, maize and beans, totaling 200 g per day). And less than once a week, they ate chicken, eggs, sea-eels, octopus, shellfish, turtles, flying foxes, pork, gwadila (which is a fruit), breadfruit, sugarcane, pandanus nuts, pomelo, and mushrooms.
The estimated average dietary macronutrient composition of the typical Kitavan diet I just described, as a percentage of total energy intake, was 69% carbohydrate, 21% fat (with saturated fat comprising 17% of total energy intake) and 10% protein. Regarding fluid intake, rain was the main source of clean drinking water. Since some salt water was used for cooking, the sodium intake ranged from 2.3 to 3 g per day, which is not as low as in other traditional populations with no access to salt.
Perhaps because of Kitavans’ high carbohydrate intake combined with a high saturated fat intake, their fasting blood lipids were not exactly optimal. Triglycerides were 106.2 ± 44.3 mg/dL in women and 100.9 ± 35.4 mg/dL in men, total cholesterol was 227 ± 46 mg/dL in women and 186 ± 31 mg/dL in men, LDL-cholesterol was 157 ± 43 mg/dL in women and 125 ± 31 mg/dL in men, and HDL-cholesterol was 49 ± 12 mg/dL in women and 41 ± 8 mg/dL in men (a desirable level is usually 60 mg/dL or beyond, although there is currently a lot of controversy surrounding the health implications of high HDL-C levels). Nevertheless, when the fatty acids in their serum cholesterol esters were analyzed, omega-3 (EPA and DHA) levels were high and, more importantly, the omega-6/omega-3 ratio was very low, owing to the low intake of linoleic acid (an omega-6 fatty acid present in the oil of most seeds and nuts, who decreases the EPA and DHA status).
Despite their high carbohydrate intake, not a single individual was overweight or obese in a sample of Kitava natives aged 40-60 years, whereas in a Swedish sex and age-matched control population, the prevalence of overweight, obesity and morbid obesity was 38%, 10%, and 2%, respectively. In line with this, Kitavans (20-86 years old) had a lower waist (cm)/height (m) ratio compared to apparently healthy Swedes (25-74 years old). It should be mentioned that Staffan didn’t detect any evidence of famine and malnutrition, which excludes these conditions as explanations for the absence of obesity. I believe the Kitava study is another source of empirical evidence that carbohydrate intake per se is not the cause of obesity. For more information regarding the flaws in the carb-insulin hypothesis of obesity, I suggest Stephan Guyenet’s excellent blog posts.
In accordance with the apparent absence of visceral obesity in Kitavans mentioned above, fasting plasma glucose levels varied between 56 and 81 mg/dL (3.1-4.5 mmol/L) in 20-86 years old Kitavans, whereas in a sample of apparently healthy Swedes aged 25-74 years, it ranged from 83 to 106 mg/dL (4.6-5.9 mmol/L). Moreover, the same Kitavans had lower fasting plasma insulin concentrations (2-6 IU/mL) compared to healthy Swedes (4-11 IU/mL). Interestingly, fasting insulinemia increased with age in Sweden, whereas in Kitava it did not. Furthermore, and partially because of their excellent insulin sensitivity and body composition, Kitavans had significantly lower fasting plasma leptin levels than healthy Swedes. Finally, Staffan noted and reported an absence of acne in 1,200 Kitavans including 300 aged 15-25 years, which is to be expected, since a major cause of acne appears to be insulin resistance combined with hyperinsulinemia.
This flies in the face of the current carb phobia and demonstrates that insulin resistance, glucose intolerance and leptin resistance are complex phenomena with multiple causes. Having said that, I do think that patients with the metabolic syndrome, glucose intolerance or type II diabetes could benefit from a lower carbohydrate, Paleolithic type diet. This was exactly what Staffan did with his type II diabetic patients, starting by recommending a lower carbohydrate diet and then increasing carbohydrate intake (from fruits and tubers) as their glucose tolerance started to improve. But just because a lower carbohydrate diet benefits these patients, that doesn’t mean carbohydrates are the cause of diabetes. This is analogous to having a broken leg and deciding to walk, thereby aggravating the problem, and then concluding that walking is bad for the legs. The same is true for protein and kidney health, where a high protein diet doesn’t appear to drive kidney disease in healthy individuals, but it might exacerbate the decline of kidney function once the disease is already installed.
As expected, Staffan found that there was a very low prevalence of hypertension among the Kitavans, as well as an apparent absence of cardiovascular disease. This is in accordance with the observations made by Horst Jüptner and Wulf Schiefenhövel when they worked as physicians on the Trobriand Islands. It is worth mentioning that according to semi-structured interviews Staffan conducted with 213 adult Kitavans, chronic exertion-related chest pain, paralysis of arms or legs, and sudden inability to speak were unknown issues to the Kitavans. And only 3 cases of spontaneous sudden death in adults were known to have occurred in the last 100 years. The dominant causes of death on Kitava were infections (primarily malaria in children), accidents, pregnancy complications and old age. And contrary to popular belief that traditional populations do not live past the age of 40, there were 125 subjects on Kitava aged 60-96 years, representing 6% of the entire population, which is in line with the average modal age of adult death for hunter-gatherers, which is 68–78 years according to a 2007 review by anthropologists Michael Gurven and Hillard Kaplan.
Strikingly, 76% of adult men and 80% of adult women on the island smoked, which demonstrates that optimal health is a complex equation with many variables and that just because one of the variables is “negative”, the net result may still be “positive”. One other variable explaining the superior health of Kitavans that I want to briefly mention is microbial exposure. Although at the time, Staffan didn’t analyze the microbiota of Kitavans (which is to be expected, since we are talking about a study conducted more than 27 years ago), his colleague Johan Frostegård from the Karolinska Institutet analyzed antibodies against phosphorylcholine, which are possible markers of helminth and microbial exposure, and found higher levels in Kitava natives compared to Swedes. Interestingly, various studies conducted by Prof. Frostegård’s team have found an inverse association between the levels of these antibodies and cardiovascular disease, which suggests they are protective. These studies add support to the hygiene/old friends hypothesis.
Note: All of the data presented here comes from Staffan’s scientific publications. The Kitava study was his PhD thesis and, in my opinion, it is still one of the best studies ever conducted on a non-westernized population. For those interested in knowing more about it, I suggest reading Staffan’s book (Food and Western Disease: Health and Nutrition from an Evolutionary Perspective) and his papers on the Kitava study, which can be obtained here:
- Antibodies against Phosphorylcholine among New Guineans Compared to Swedes: An Aspect of the Hygiene/Missing Old Friends Hypothesis.
- Antitreponemal antibodies leading to autoantibody production and protection from atherosclerosis in Kitavans from Papua New Guinea.
- Atheroprotective natural anti-phosphorylcholine antibodies of IgM subclass are decreased in Swedish controls as compared to non-westernized individuals from New Guinea
- Determinants of serum triglycerides and high-density lipoprotein cholesterol in traditional Trobriand Islanders: the Kitava Study.
- Large differences in serum leptin levels between nonwesternized and westernized populations: the Kitava study.
- Low serum insulin in traditional Pacific Islanders–the Kitava Study.
- Age relations of cardiovascular risk factors in a traditional Melanesian society: the Kitava Study.
- Haemostatic variables in Pacific Islanders apparently free from stroke and ischaemic heart disease–the Kitava Study.
- Lipoprotein composition and serum cholesterol ester fatty acids in nonwesternized Melanesians.
- Trace element concentrations in hair of subjects from two South Pacific Islands, Atafu (Tokelau) and Kitava (Papua New Guinea).
- Apparent absence of stroke and ischaemic heart disease in a traditional Melanesian island: a clinical study in Kitava.
- Acne vulgaris: a disease of Western civilization.
5. One of the main reasons why traditional people don’t suffer from chronic health problems such as type-1 and type-2 diabetes, cardiovascular disease, and colon cancer is undoubtedly that they aren’t exposed to all of the proinflammatory stimuli that are produced by modern, westernized diets and lifestyles. This idea is supported by a large body of evidence which indicates that chronic inflammation is a driving force behind many of the diseases of civilization. Could you provide a little detail as to how inflammation causes disease? What are the mechanisms that link chronic inflammation with the typical non-communicable diseases of civilization?
It’s important to acknowledge that the goal of inflammation is to protect us from infectious agents (such as viruses and bacteria), toxins and other environmental aggressions, and to initiate repair processes after a surgery or an injury (such as a torn meniscus, or an ankle sprain, for instance). Inflammation is thus a normal and crucial phenomenon characterized by the recruitment of various cells of the immune system. Since these recruited cells will have increased energy and nutrient needs, there will be a competition for those resources between the immune system and many other organs and systems of the body (such as the musckuloskeletal system, adipose tissue, and the brain, among others). Therefore, various metabolic, neurological and hormonal changes must occur to supply more nutrients to the activated immune system and less so to the other organs, while at the same time limiting nutrient access to infectious organisms (such as various metal ions, namely iron, zinc, and manganese, that “feed” bacteria). Those alterations include:
- Insulin resistance in liver, muscle and adipose tissue
Activated immune cells (leukocytes) have increased glucose needs, but there is competition for this nutrient between these cells and the cells of the muscle (myocytes) and adipose tissue (adipocytes). Leukocytes circumvent this problem by secreting various proteins (such as cytokines) that cause insulin resistance in myocytes and adipocytes. This in turn will reduce glucose uptake by the latter and redirect it to the former. Moreover, certain cytokines also cause insulin resistance in liver cells (hepatocytes), which increases glucose output by the liver, hence leading to more glucose being available to immune cells.
- Loss of muscle mass
The amino acid glutamine is another important nutrient for activated leukocytes. Since muscle is an important “reservoir” of glutamine and of various other amino acids (some of which can be used by the liver to produce glucose), certain cytokines secreted by leukocytes will cause muscle protein loss, thereby increasing the allocation of glutamine and glucose (produced in the liver by using certain amino acids, coming from muscle, as raw material) to the immune system.
- Increased coagulation
Part of the complex inflammatory response to trauma and injury involves the activation of mechanisms to increase coagulation, in order to reduce the loss of blood.
- Altered lipoprotein metabolism
Lipoproteins (and the lipids they contain, such as cholesterol) have important roles in the immune response and in repair mechanisms. Therefore, during an inflammatory response, various phenomena can be observed. For instance, there is a decrease in HDL particle concentration and size, as well as a reduction in one important HDL protein called apo-A1. This will decrease the uptake of cholesterol by the liver, thereby redirecting more cholesterol to immune cells, cells of the adrenal glands that use cholesterol to produce important hormones, and also cells in need of cholesterol to repair damaged membranes. There’s also an increase in small dense LDL particles, which more easily direct cholesterol to damaged sites.
- Decreased availability of iron, zinc and manganese
This happens in order to limit pathogenic organisms’ access to these minerals.
- Bone mineral loss
Calcium and phosphate are important for activated leukocytes. Since bones serve as the biggest storage compartment for these minerals, leukocytes will release cytokines to increase bone resorption, thereby gaining more access to those nutrients.
- Decreased Vitamin B6 levels
The uptake of vitamin B6 by activated leukocytes increases during inflammation, as it is needed for various functions. Therefore, its blood levels decrease significantly.
- Reduced levels of Vitamin D
Inflammation can lead to a reduction in blood levels of vitamin D, presumably because of the potential role of this molecule in downregulating the recruitment of immune cells.
- Decreased testosterone levels
Because inflammation is critical for survival and has a high energy demand, all systems and functions that are in need of energy and that are not important for short-term survival, such as sex and reproduction, will be put on hold. Since testosterone is important for libido and fertility, increasing the chances of sex and reproduction, molecules produced by activated immune cells may decrease testosterone levels, in order to obtain as much energy and nutrients as possible.
- Depressive-like symptoms
Inflammation induces neurological changes that decrease the drive for a human being to do basic normal daily activities. This is called sickness behaviour and resembles depression. The purpose of this is to reduce energy expenditure by the brain, muscle and other organs, thereby increasing the allocation of resources to the activated immune system.
- Sleep changes
REM (Rapid Eye Movement) sleep demands a significant amount of energy. For this reason, inflammation decreases REM sleep. This not only decreases energy expenditure by the brain, but it also leads to fatigue, thereby increasing the amount of time the affected individual spends in bed, which further preserves energy for the immune system.
If they remain uncontrolled, all of these inflammation-induced perturbations can compromise our health, well-being, survival and reproduction. This is why a normal and healthy inflammatory response doesn’t last long. In fact, inflammation normally ceases in a matter of days, or at the most weeks, once the trigger is gone and the healing process has occurred. However, the modern diet and lifestyle can activate numerous inflammatory pathways, leading to a state of low-grade chronic inflammation, which in turn will trigger the mechanisms described above. In the long-run, this can increase the risk for the metabolic syndrome, type II diabetes, non-alcoholic fatty liver disease, hypertension, stroke, myocardial infarction, certain types of cancer, depression, Alzheimer’s disease, Parkinson’s disease, osteoporosis, sarcopenia (loss of muscle mass and strength), various nutritional deficiencies, and sleep disturbances, among other health problems. Furthermore, chronic inflammation exacerbates osteoarthritis and autoimmune diseases, decreases the (adaptive immune) response to infections, and is being increasingly recognized as an important cause of premature aging.
6. What other factors besides the aforementioned immune/inflammation-related parameters do you consider to be particularly important up in all of this? I.e., what is it about the body of the modern man that makes it a lot more susceptible to various illnesses and health issues than the body of a hunter-gatherer?
Your question reminds me of a common counter-argument used to dismiss studies like the Kitava study. That argument states that hunter-gatherers and other non-westernized individuals are genetically protected against the typical diseases that occur in industrialized countries. This doesn’t appear to be true. In fact, various studies have shown that when those populations adopt a western diet and lifestyle their risk for chronic degenerative diseases is similar or even increased compared to modern populations. Moreover, when they return to their original traditional lifestyle many disease markers or symptoms return to normal. These data suggest that the superior health markers, body composition and physical fitness of hunter-gatherers and other populations minimally affected by modern habits are not due primarily to genetics, but first and foremost to the environment. This occurs because the people in question are not adapted to the ecological niches in which they live and therefore don’t thrive in their environment.
Another line of evidence supporting the above idea comes from studies conducted among westernized populations. Various observational and intervention studies suggest that many consequences of industrialization and westernization, such as physical inactivity, consumption of hypercaloric western-like diets, altered sleep patterns, and exposure to pollutants, among other things, worsen various health biomarkers and increase the risk for chronic degenerative diseases. More importantly, there are many intervention trials showing that when people return to a more traditional-like lifestyle, such as by exercising more, improving their sleep patterns or changing from a western-type diet to a diet with more whole foods, less processed and ultra-processed foods, and an adequate energy balance, many health biomarkers improve. This suggests that there is a mismatch between our “ancient”, evolutionary determined physiology and the modern environment, which means that we are probably more adapted to a traditional way of life.
Notwithstanding, I do recognize that several genetic and epigenetic changes have occurred throughout recent human history. Therefore, different individuals will obviously react differently to the same environment. Nevertheless, the Industrial Revolution and the Modern Age, which gave rise to the western lifestyle, represent only 7 and 4 human generations, respectively, and were marked by radical and fast changes in lifestyle and diet coupled with political and social stability, less physical trauma, and improved public health actions (better sanitation, vaccination, antibiotics, quarantine policies, and medical care), that significantly reduced mortality and decreased impaired reproductive fitness as a selection pressure.
Moreover, chronic degenerative diseases involve numerous genes and normally occur in the post-reproductive years, when the impetus for genetic adaptations is greatly reduced. As such, I find it highly unlikely that genetic adaptations that allow us to thrive on a western diet and lifestyle have occurred. In my view, two different individuals, when exposed to the same modern environment (e.g. western diet, physical inactivity, insufficient and inadequate sleep, chronic psychological stress, insufficient or excessive sun exposure, use of recreational drugs, smoking, pollution) will always express a suboptimal phenotype. This may or may not be considered pathological, depending on genetic variants and differences in gene expression regulation (such as epigenetic variations). Of course, when we talk about a health professional giving specific advice or treatment to a patient, the focus should be on individualization; however, in my view, always under the umbrella of a less westernized lifestyle.
7. Many other environmental/lifestyle factors besides diet are known to affect our health, including physical activity levels and sun exposure. What do you personally feel is most important with respects to human health promotion? In your opinion, are there any health-related topics that don’t get the attention they deserve?
Like you, I also feel that diet (albeit very important) is only part of the picture. As I said above, health is a big equation, where the net result is determined by various variables, which include:
– Physical activity
According to a 2012 paper published in the Lancet that estimated physical inactivity in adults (aged 15 years or older) from 122 countries, a large proportion of individuals in industrialized countries did not meet any of the following criteria: i) 30 min of moderate-intensity physical activity on at least 5 days every week; ii) 20 min of vigorous-intensity physical activity on at least 3 days every week.
This is in stark contrast to the habits of healthy adults in traditional populations that still follow a pre-industrial lifestyle. For instance, among the Igloolik Inuit, from Canada, the Hadza of Tanzania, the Tsimané horticulturalists of Bolivia and the Ache hunter-gatherers of Paraguay, the daily estimated physical activity level is considered moderate to active in women and vigorously active in men. Likewise, the Masaai, Luo and Kamba from rural Kenya maintain a moderate to active physical activity level. Finally, the horticulturalists from Kitava that Staffan studied had an estimated physical activity level equivalent to 1.7 times their basal metabolic rate.
Based on these findings, it can be concluded that high regular physical activity levels (much beyond the current minimum recommended 150 min per week) appears to have been the norm during human evolution and that the current inactivity and sedentary pattern adopted by populations of industrialized countries is neither normal nor desirable. Physical inactivity leads to a suboptimal phenotype expression and can cause obesity, inflammation, loss of muscle mass, insulin resistance, dyslipidemia, endothelial dysfunction, elevated blood pressure, and reduced antioxidant defense mechanisms, among various other disturbances, thereby increasing the risk for type 2 diabetes, coronary artery disease, stroke, congestive heart failure, intermittent claudication, gallstones, various types of cancer, age-related cognitive dysfunction, and osteoporosis, among other diseases. As expected, many of the disturbances mentioned are improved or even reversed with an adoption of a balanced exercise program.
– Psychological stress
Numerous studies have found associations between chronic stress and premature aging, as well as an increased risk for various diseases and health problems, which is partly because stress activates inflammatory responses. Interestingly, a systematic review and meta-analysis of longitudinal observational studies, published in 2016 in the journal Heart found an association between poor social relationships and the risk for coronary heart disease and stroke. Moreover, there is also evidence from intervention studies (albeit not the best when it comes to methodological quality) that stress-management techniques, such as meditation, might reduce cortisol, blood pressure, heart rate, triglycerides and some inflammatory markers.
– Sun exposure
The sun emits electromagnetic radiation, which encompasses a large spectrum of wavelengths. Of these, only infrared, visible light, and ultraviolet (UV) radiation are able to reach the earth’s surface and hence our skin. So far, most of the research regarding the effects of the sun on human health has focused on UV radiation, which is divided into UVC, UVB and UVA. Virtually no UVC radiation reaches the earth’s surface, except at extremely high altitudes, since it is efficiently absorbed by the stratospheric ozone layer. Ozone also absorbs most of the UVB and UVA radiation. Indeed, only about 0.1% of UVB radiation and 5% of UVA radiation reach the surface of our planet. In contrast, 39% of visible radiation and 56% of infrared radiation can reach the earth’s surface. Nevertheless, even these small levels of UVA and UVB radiation have a significant impact on the human physiology, the most studied being the production of vitamin D, which occurs in the epidermis (the outer layer of our skin) when it is stimulated by UVB. Vitamin D will then be converted in different cells of various tissues and organs into more “bioactive” molecules that will affect the expression of approximately 2000 genes and regulate many cellular processes.
But UVA and UVB have other effects beyond those related to Vitamin D. For instance, evidence from epidemiological and animal studies suggests that UVA and UVB radiation exposure might prevent or even suppress the development of immune-mediated diseases such as asthma, multiple sclerosis and type 1 diabetes through various vitamin D-independent mechanisms. Also, clinical trials with UV radiation have shown positive effects in some immune-related skin disorders, such as psoriasis, vitiligo, localized scleroderma and atopic dermatitis. Moreover, there is evidence that exposure to UVA radiation enhances blood flow and reduces blood pressure in humans. Furthermore, when we are exposed to the sun, especially UVB radiation, our skin increases the production of an opioid called ß-endorphin that could be released into blood and hence reach various tissues and organs, such as the brain, where it could cause mood improvements, relaxation, and alleviation of pain.
ß-endorphin (and other chemicals of the hypothalamic-pituitary-adrenal axis produced in the skin) may also be involved in the seasonal depressive disorder that affects some people during the winter time. Another example of the vitamin D-independent effects of the sun is circadian synchronicity. It is well known that virtually all cells in our bodies, including the ones in the skin, contain genes that control our circadian rhythm. Interestingly, when human skin is exposed to UVB radiation the expression of those genes is increased. Finally, there is the direct effect of light on our central nervous system. Indeed, bright-light therapy has been shown to be effective for seasonal depression and also for jet-lag symptoms. Many more examples could be discussed, but I think this is enough to support the idea that replacing sun exposure with vitamin D3 (either coming from supplements or foods) is, in my view, a simplistic approach.
– Sleep patterns and circadian rythms
Various experiments under controlled conditions have shown that reducing the number of hours of sleep in humans decreases endothelial-dependent vasodilation and increases insulin resistance and inflammatory markers. Moreover, insufficient sleep, as well as shift work, is associated with cardiovascular disease, certain types of cancer, autoimmune thyroid diseases, rheumatoid arthritis and increased mortality. Finally, exposure to light at atypical hours (nighttime) (common in industrialized nations) greatly reduces the secretion of melatonin (a hormone that has significant anti-oxidant and anti-inflammatory effects) and disrupts circadian rhythms.
– Pollution and smoking
Atmospheric air pollutants and chemical constituents of tobacco can activate inflammatory responses and cause oxidative stress, among other disturbances, which could accelerate ageing and increase the risk for various diseases. Furthermore, pesticides, industrial chemicals, and hazardous waste products may act as endocrine disruptors and have been suspected of acting as promoters of hormone-dependent cancers (such as breast and prostate cancer), cardiovascular disease, insulin resistance and type 2 diabetes.
– Overuse of antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitors (PPIs), as well as altered microbial exposure
All of the above drugs have a therapeutic role in certain conditions and diseases. One thing is for a physician to prescribe them when there is a need to do so and another is for someone to (over)use them without checking with their physician and when they are not needed (for instance, taking an antibiotic to “fight” a flu episode or an NSAID to reduce a mild exercise-induced muscle pain). The overuse of drugs, especially when it is coupled with the consumption of a western diet (low in fruits and vegetables and high in sugar, salt, refined grains, alcohol and ultra-processed foods that combine sugar, fat, flour, salt and various additives, especially emulsifiers), can change the delicate and complex balance of our gut’s ecosystem, leading to intestinal dysbiosis and increased intestinal permeability, both of which are believed to play an important role in the development and exacerbation of various chronic degenerative diseases.
Interestingly, the few studies that have analysed the microbiota (not only the one present in the gut, but also in the skin) of hunter-gatherers (such as the Hadza, the Yanomami, and the Pygmies of Cameroon and Central African Republic) show it to be vastly different from the microbiota of westerners, which is due not only to different diets and use of certain drugs, but also to the vastly different degrees of exposure to soil, plant, animal and human-derived microorganisms and helminths.
In my opinion, this makes it extremely difficult to reach definitive conclusions regarding the microbiota. Nevertheless, I think it is reasonable to recommend to people that they spend more time outside in contact with nature (which also reduces stress); exercise regularly; properly regulate their sleep and circadian rhythms; avoid overusing antibiotics, NSAIDs, and PPIs; limit their consumption of processed and ultra-processed foods, isolated sugars, and refined grains; and adopt a more traditional-like diet with a higher amount of vegetables, fruits, tubers and other whole foods containing fermentable carbohydrates.
8. To a Darwinist such as myself, it makes complete sense that traditional people who live in an environment that bears resemblance to the milieu of our Paleolithic forebears are lean and fit. That said, our primal ancestors obviously didn’t live in a utopia. Many aspects of their way of life probably seem unappealing to the typical modern man or woman. What do you consider to be the less positive aspects of the hunter-gatherer existence? Is there anything about the health or fitness status or lifestyle of hunter-gatherers or other traditional people that isn’t that great?
Although it seems very appealing to live like our ancestors did for most of our time on earth as hominins, such as is the case for the various traditional populations we discussed, we cannot forget that infections killed and continue to kill many people (especially children) n various developing countries. In fact, as Gurven and Kaplan point out in their excellent 2007 paper titled Longevity Among Hunter-Gatherers: A Cross-Cultural Examination, “…infant mortality is over 30 times greater among hunter-gatherers, and early child mortality is over 100 times greater than encountered in the United States.” One of the great conquests of modern times was the significant decrease in infant mortality.
Moreover, our Paleolithic ancestors may have endured some periods of famine. Although the fossil record and studies of contemporary hunter-gatherers suggest they had a much better diet than Neolithic farmers I have a hard time believing that they had access to plenty of food all the time. Furthermore, if you got bitten by a snake, attacked by a wild animal, fell from a tree or had any other accident, your chances of survival and of full recovery were slim. We cannot ignore how lucky we are to have access to cutting-edge medical care. Finally, some of us (but unfortunately not all and there are many sad ongoing examples) live in an environment characterized by less physical trauma and good political and social stability.
9. What do you personally feel are the most important lessons we can learn from hunter-gatherers and other traditional people?
All of the aforementioned traditional people differ with respects to their diet and lifestyle habits, which is due to differences in geographic location, climate, season, and the overall ecosystems exploited. Nevertheless, their lifestyles and also the lifestyles of most other long-lived healthy individuals have certain characteristics in common that we can try to mimic without losing the advantages of the modern world, such as by…
- Going for a more omnivorous traditional-like diet composed of whole foods.
- Increasing daily physical activity and following an exercise program.
- Getting regular (but never excessive) sun exposure.
- Spending more time in contact with nature.
- Living more in synch with the daily variation in light availability and adopting a more “natural” circadian rhythm. This might simply mean minimizing exposure to bright light (especially blue light) in the evening, getting to bed earlier, having a regular bedtime and wake time, and increasing one’s exposure to light during the day.
- Minimizing exposure to xenobiotics, by way of living in areas with lower air pollution and reduced hazardous waste products, avoiding first and second-hand tobacco smoke, minimizing the intake of foods containing pesticides, replacing plastic food and beverage containers with glass ones, and reducing exposure to industrial chemicals.
- Adopting stress management techniques, be it meditation, a hobby, a sport, spending time with friends and loved ones, or any other strategy that gets the job done. Personally, I do yoga and meditation, and I try to stay away from stressful situations (e.g. avoiding unnecessary conflicts, not spending too much time on social media, walking instead of taking the car during rush hour even if it takes me a little longer to get from A to B).
- Having a sense of purpose. I am not religious (religion can in a way can help give one a sense of purpose), but I have many reasons to wake up in the morning and to keep doing what I do, and I try to remember those reasons on a regular basis.
- Having fun.
- Choosing positive social relationships. Personally, I try to follow Shakespeare’s famous quote: Love all, trust a few, do wrong to none.
10. There are many misconceptions about nutrition and medicine floating around on the internet and among the general public. Please comment on one that you feel is particularly prevalent and/or destructive.
Indeed, there are many misconceptions. Some are harmless, but others might have adverse consequences. The one that bothers me the most is the idea that you can eat whatever food you want, as long as you remain in an adequate energy and macronutrient balance. This implies that food quality doesn’t matter, only quantity does. I think most of your readers pay attention to the types of foods they include in their diets, but that is not the case in many other circles, especially among young apparently healthy people who exercise regularly.
There is no doubt that exercising more and adjusting energy intake and the macronutrient distribution of the diet will improve body composition and various biomarkers, but that doesn’t mean that unhealthy food choices don’t impact negatively on health in the long-run (e.g. increasing the risk for certain types of cancer, cardiovascular disease, autoimmune and neurodegenerative diseases). Energy balance and macronutrient distribution matter, but so does food quality.
11. If a typical obese and metabolically deranged westerner came up to you and asked you what you’d recommend that he should do to improve his health and lose weight, what would you tell him? Assume that the person isn’t severely sick or requires continuous medical care.
Since obesity can cause many disturbances that demand a personalized approach, I would probably ask her/his physician to run a battery of tests and apply a comprehensive health and lifestyle questionnaire, besides conducting anthropometric measurements, before I would make any recommendations. Having said that, a general approach would be: regular exercise under the expert guidance of an exercise professional and consumption of a moderately calorie-restricted traditional-like diet with a fairly high protein content (in order to decrease the loss of lean mass caused by the energy restriction), as well as the lifestyle changes I mentioned above.
12. What do you consider to be the most important things Darwinian/evolutionary medicine has to contribute to the conventional health care system?
Using the lens of evolutionary medicine allows us to understand that we are facing a mismatch between our old-physiology and the rapid, radical and still ongoing changes in lifestyle and diet. Darwin said that natural selection and the conditions of existence are the forces behind evolution, the latter being more powerful. We need to realize that constantly changing the conditions of existence (our environment) has many adverse consequences.
13. If you were to list 5 scientific papers that you think everyone who’s interested in health and medicine should read, what papers would you choose?
If I may, I will list 20 papers instead of just 5. These are:
- Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O’Keefe JH, Brand-Miller J. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr. 2005 Feb;81(2):341-54.
- Frassetto L, Morris RC Jr, Sellmeyer DE, Todd K, Sebastian A. Diet, evolution and aging–the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet. Eur J Nutr. 2001 Oct;40(5):200-13.
- Jönsson T, Olsson S, Ahrén B, Bøg-Hansen TC, Dole A, Lindeberg S. Agrarian diet and diseases of affluence–do evolutionary novel dietary lectins cause leptin resistance? BMC Endocr Disord. 2005 Dec 10;5:10.
- Kuipers RS, Joordens JC, Muskiet FA. A multidisciplinary reconstruction of Palaeolithic nutrition that holds promise for the prevention and treatment of diseases of civilisation. Nutr Res Rev. 2012 Jun;25(1):96-129.
- Cordain L. Cereal grains: humanity’s double-edged sword. World Rev Nutr Diet. 1999;84:19-73.
- McDade TW. Early environments and the ecology of inflammation. Proc Natl Acad Sci USA. 2012 Oct 16;109 Suppl 2(Supplement_2):17281–8.
- Straub RH, Cutolo M, Buttgereit F, Pongratz G. Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J Intern Med. 2010 Jun;267(6):543-60.
- Pareja-Galeano H, Garatachea N, Lucia A. Exercise as a Polypill for Chronic Diseases. Prog Mol Biol Transl Sci. 2015;135:497-526.
- Melnik BC, Schmitz G. Milk’s Role as an Epigenetic Regulator in Health and Disease. Diseases. 2017 Mar 15;5(1). pii: E12.
- Renz H, Holt PG, Inouye M, Logan AC, Prescott SL, Sly PD. An exposome perspective: Early-life events and immune development in a changing world. J Allergy Clin Immunol. 2017 Jul;140(1):24–40.
- Ruiz-Núñez B, Pruimboom L, Dijck-Brouwer DA, Muskiet FA. Lifestyle and nutritional imbalances associated with Western diseases: causes and consequences of chronic systemic low-grade inflammation in an evolutionary context. J Nutr Biochem. 2013 Jul;24(7):1183-201.
- Shen-Orr SS, Furman D, Kidd BA, Hadad F, Lovelace P, Huang Y-W, et al. Defective Signaling in the JAK-STAT Pathway Tracks with Chronic Inflammation and Cardiovascular Risk in Aging Humans. Cell Syst. 2016 Oct 26;3(4):374–4.
- Booth FW, Roberts CK, Thyfault JP, Ruegsegger GN, Toedebusch RG. Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms. Physiol Rev. 2017 Oct 1;97(4):1351-1402.
- Franceschi C, Garagnani P, Vitale G, Capri M, Salvioli S. Inflammaging and “Garb-aging.” Trends Endocrinol Metab. 2017 Mar;28(3):199-212.
- Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. . 2011 Jan;91(1):151–75.
- Serhan CN. Treating inflammation and infection in the 21st century: new hints from decoding resolution mediators and mechanisms. FASEB J. 2017 Apr;31(4):1273–88.
- Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Br J Nutr. 2000 Mar;83(3):207-17.
- Crawford MA, Broadhurst CL, Guest M, Nagar A, Wang Y, Ghebremeskel K, Schmidt WF. A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution. Prostaglandins Leukot Essent Fatty Acids. 2013 Jan;88(1):5-13.
- Gurven MD, Trumble BC, Stieglitz J, Blackwell AD, Michalik DE, Finch CE, Kaplan HS. Cardiovascular disease and type 2 diabetes in evolutionary perspective: a critical role for helminths? Evol Med Public Health. 2016 Sep 25. pii: eow028. [Epub ahead of print].
- Frostegård J. Immunity, atherosclerosis and cardiovascular disease. BMC Med. 2013 May 1;11:117.
I would also recommend Staffan’s marvelous book (Food and Western Disease: Health and Nutrition from an Evolutionary Perspective), that compiles what he has written in various scientific papers, as well as many other important and often forgotten and unrecognized topics.
14. What are your plans moving forward? Will you continue your research on Paleolithic nutrition and other related topics?
I want to continue to dedicate a part of my time to communicate science both for health professionals and the lay public in a way that people can understand and apply, but I also want to take part in research projects aimed at studying the diet, lifestyle, and biomarkers of traditional populations, which are (sadly) rapidly disappearing.
15. Any last thoughts?
For health professionals, I would say that when faced with a complex problem in terms of health and disease, the best approach might be to try to use all of the available evidence (including not only systematic reviews of observational studies and clinical trials, but also animal and in vitro data) combined with an evolutionary approach, an open-mind, and a healthy dose of skepticism.
For those who care about their health and want to know how to make better choices in terms of diet and lifestyle, my advice is: get your priorities right. This means following a traditional diet (composed of whole foods and very little western foods), exercising regularly and increasing daily physical activity levels, paying attention to circadian rhythms, getting regular (but never excessive) sun exposure, spending more time in nature, and decreasing exposure to pollutants. It’s also important to manage one’s stress levels, have a purpose in life, spend time with loved ones, and above all strive to be happy and have fun. These things should be in order before one focuses on specific foods and macronutrient and micronutrient adjustments. Having said that, if you have a specific disease or condition, you should consult with your health professional to personalize your diet and lifestyle according to your requirements and limitations.