10 Scientific Papers That Can Transform Your Understanding of Health & Medicine

woman-readingOver the years I’ve read a lot of scientific articles on nutrition, health, and medicine. One of the things this has shown me is that there’s a lot of bad science and poorly performed research studies out there. However, if you look in the right places, you can also find some truly great stuff. In this post I wanted to share 10 of my favorite research papers, which I highly recommend that everyone should read. Not just because doing so will make you more knowledgeable about diet and health, but because the information contained in these papers can prove invaluable in your quest for a strong, lean, and fit body.

The science of Darwinian Medicine

If you read about health, nutrition, and medicine in the popular press or listen to what your general health practitioner has to say about the science underlying various forms of supplements, diets, drugs, and medical interventions, you may get the impression that conventional medical interventions, official food pyramids, and public health advice coming out of governmental institutions are built on a foundation of extremely solid scientific research – and that there’s little research supporting diets, medical treatments, etc. that aren’t included in this system.

As I’ve repeatedly highlighted here on the blog, this is not actually the case…

Certainly, many alternative forms of medicine and nutrition (e.g., homeopathy, vegan diets) don’t have any support in science. However, when it comes to the medical interventions and nutritional principles (e.g., Paleolithic diets, microbiome restoration, ancestral exercise) I talk about on this site, there is a pile of scientific evidence. The 10 articles below, which all cover topics that are somehow connected to Darwinian Medicine, can give you a good overview of this research.

I’ll go as far as to say that if you read (and understand) the research articles in this post, you’ll know more about the true causes and solutions of chronic non-infectious diseases and health disorders than the vast majority of medical doctors out there. If you ever come across a health practitioner who doubts that diet is important in the context of health and disease or someone who says there is little or no science supporting Paleolithic diets, evolutionary/Darwinian medicine, etc., then you may consider forwarding him this post. 

I realise that a lot of people don’t have the time or will to read all 10 articles – and that’s fine. My suggestion for those who’d like to dig into the science in this post, but don’t have hours to spare, is to go through the abstracts, and then pick a couple of full-text papers to read when you have the time.

I’ve only included review papers and articles that summarize the research on various topics, not single studies or systematic reviews. Also, I’ve only included papers that can be freely accessed online and that don’t require a Ph. D. in science to understand. The articles are in no particular order.

Without further ado, let’s get to it…

1. Comparison with ancestral diets suggests dense acellular carbohydrates promote an inflammatory microbiota, and may be the primary dietary cause of leptin resistance and obesity

Abstract: A novel hypothesis of obesity is suggested by consideration of diet-related inflammation and evolutionary medicine. The obese homeostatically guard their elevated weight. In rodent models of high-fat diet-induced obesity, leptin resistance is seen initially at vagal afferents, blunting the actions of satiety mediators, then centrally, with gastrointestinal bacterial-triggered SOCS3 signaling implicated. In humans, dietary fat and fructose elevate systemic lipopolysaccharide, while dietary glucose also strongly activates SOCS3 signaling. Crucially however, in humans, low-carbohydrate diets spontaneously decrease weight in a way that low-fat diets do not. Furthermore, nutrition transition patterns and the health of those still eating diverse ancestral diets with abundant food suggest that neither glycemic index, altered fat, nor carbohydrate intake can be intrinsic causes of obesity, and that human energy homeostasis functions well without Westernized foods containing flours, sugar, and refined fats. Due to being made up of cells, virtually all “ancestral foods” have markedly lower carbohydrate densities than flour- and sugar-containing foods, a property quite independent of glycemic index. Thus the “forgotten organ” of the gastrointestinal microbiota is a prime candidate to be influenced by evolutionarily unprecedented postprandial luminal carbohydrate concentrations. The present hypothesis suggests that in parallel with the bacterial effects of sugars on dental and periodontal health, acellular flours, sugars, and processed foods produce an inflammatory microbiota via the upper gastrointestinal tract, with fat able to effect a “double hit” by increasing systemic absorption of lipopolysaccharide. This model is consistent with a broad spectrum of reported dietary phenomena. A diet of grain-free whole foods with carbohydrate from cellular tubers, leaves, and fruits may produce a gastrointestinal microbiota consistent with our evolutionary condition, potentially explaining the exceptional macronutrient-independent metabolic health of non-Westernized populations, and the apparent efficacy of the modern “Paleolithic” diet on satiety and metabolism.

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My comment: Why have obesity rates skyrocketed over the last couple of decades? Can we simply blame our rapidly expanding waistlines on a lack of self-control and poor willpower? No, we can’t. As I’ve discussed in length here on the blog, to really be able to understand why so many people are now overweight, we also have to consider how our food choices, lifestyle, and environment impact our hormone levels, microbiome, and immune system, among other things. In this paper, Ian Spreadbury brings together data from several different fields of science and formulates a theory that can help explain why modern diets, in particular those high in refined grains, sugar, and other so-called “acellular carbohydrates”, promote overeating, leptin resistance, and fat gain. This review paper is definitely worth a read. Also, the reference list is a gold mine for those who are particularly interested in these topics.

2. The western diet and lifestyle and diseases of civilization

Abstract: It is increasingly recognized that certain fundamental changes in diet and lifestyle that occurred after the Neolithic Revolution, and especially after the Industrial Revolution and the Modern Age, are too recent, on an evolutionary time scale, for the human genome to have completely adapted. This mismatch between our ancient physiology and the western diet and lifestyle underlies many so-called diseases of civilization, including coronary heart disease, obesity, hypertension, type 2 diabetes, epithelial cell cancers, autoimmune disease, and osteoporosis, which are rare or virtually absent in hunter–gatherers and other non-westernized populations. It is therefore proposed that the adoption of diet and lifestyle that mimic the beneficial characteristics of the preagricultural environment is an effective strategy to reduce the risk of chronic degenerative diseases.

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My comment: If you could only read one article on diet and health, this paper, which is written by some of the most prominent and respected researchers involved in the ancestral health community, would be a very good choice. The article investigates how the western diet and lifestyle affects our gene expression and immunity and looks into the true underlying causes of chronic diseases such as colorectal cancer, type-2 diabetes, and osteoporosis.

3. Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms

Abstract: Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness. Microbes may do this through two potential strategies: (i) generating cravings for foods that they specialize on or foods that suppress their competitors, or (ii) inducing dysphoria until we eat foods that enhance their fitness. We review several potential mechanisms for microbial control over eating behavior including microbial influence on reward and satiety pathways, production of toxins that alter mood, changes to receptors including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain. We also review the evidence for alternative explanations for cravings and unhealthy eating behavior. Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating.

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My comment: If you’ve been reading my articles on the gut-brain axis and the role bacteria in our gut play in shaping our mood and behaviour, you probably recognize this excellent article. This groundbreaking paper – which revolutionizes our understanding of obesity and eating behaviour – will change how you think about the concept of “free will” and may leave you wondering whether it’s you (the human host) or the microbes in your gut (the gut microbiome) that control your appetite and eating behaviour.

4. Lifestyle and nutritional imbalances associated with Western diseases: causes and consequences of chronic systemic low-grade inflammation in an evolutionary context

Abstract: In this review, we focus on lifestyle changes, especially dietary habits, that are at the basis of chronic systemic low grade inflammation, insulin resistance and Western diseases. Our sensitivity to develop insulin resistance traces back to our rapid brain growth in the past 2.5 million years. An inflammatory reaction jeopardizes the high glucose needs of our brain, causing various adaptations, including insulin resistance, functional reallocation of energy-rich nutrients and changing serum lipoprotein composition. The latter aims at redistribution of lipids, modulation of the immune reaction, and active inhibition of reverse cholesterol transport for damage repair. With the advent of the agricultural and industrial revolutions, we have introduced numerous false inflammatory triggers in our lifestyle, driving us to a state of chronic systemic low grade inflammation that eventually leads to typically Western diseases via an evolutionary conserved interaction between our immune system and metabolism. The underlying triggers are an abnormal dietary composition and microbial flora, insufficient physical activity and sleep, chronic stress and environmental pollution. The disturbance of our inflammatory/anti-inflammatory balance is illustrated by dietary fatty acids and antioxidants. The current decrease in years without chronic disease is rather due to “nurture” than “nature,” since less than 5% of the typically Western diseases are primary attributable to genetic factors. Resolution of the conflict between environment and our ancient genome might be the only effective manner for “healthy aging,” and to achieve this we might have to return to the lifestyle of the Paleolithic era as translated to the 21st century culture.

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My comment: Just like research paper number 2 in this post, this paper provides an overarching look at the many elements of modern lifestyles that cause chronic low-grade inflammation and summarizes the true causes of Western diseases. It’s a bit more technical than some of the other articles in this post, but if you have the time, I definitely recommend reading through the whole thing.

5. How is Darwinian medicine useful?

Introduction: Evolution by natural selection has been biology’s organizing principle for more than a century, but only in the last few decades has it been applied to the social sciences and medicine. Its application to medicine, known as evolutionary or Darwinian medicine, uses an evolutionary perspective to understand why the body is not better designed and why, therefore, diseases exist at all. This article outlines some basic principles of Darwinian medicine, summarizes the usefulness of evolutionary principles for medicine, and provides some examples from key literature sources.

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My comment: This short article takes a look at the evolutionary explanation of some common health conditions such as obesity and anxiety disorders and explains how an evolutionary approach can fundamentally change how we think about the body and disease.

6. Organic fitness: physical activity consistent with our hunter-gatherer heritage.

Abstract: Many of the pervasive health concerns in modern society are the result of diet and lifestyle choices that are at odds with the evolutionary milieu for which we remain genetically adapted. This systematic displacement from a very physically active lifestyle in a natural outdoor environment to a sedentary indoor lifestyle may be at the root of many chronic diseases that are endemic in our culture. A proposed solution is to simulate indigenous human activity patterns in a way that is possible and practical for individuals to achieve. Suggestions for exercise mode, duration, intensity, and frequency are outlined, with a focus on realigning our daily physical activities with the archetype that is encoded within our genome. In a sedentary individual, this type of daily physical activity should help confer the robust vigorous health that enabled our ancestors to survive and thrive as hunter-gatherers in the wild.

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My comment: How should someone who’s looking to achieve multifacated fitness and robust health design their training program? What can evolution and studies of hunter-gatherers tell us about what types of exercise patterns we are best adapted for? These are some of the many important questions that you’ll find answered in this paper. Definitely worth a read, particularly for those who aren’t already familiar with the principles of “Paleo fitness“.

7. Starving our Microbial Self: The Deleterious Consequences of a Diet Deficient in Microbiota-Accessible Carbohydrates

Abstract: The gut microbiota of a healthy person may not be equivalent to a healthy microbiota. It is possible that the Western microbiota is actually dysbiotic and predisposes individuals to a variety of diseases. The asymmetric plasticity between the relatively stable human genome and the more malleable gut microbiome suggests that incompatibilities between the two could rapidly arise. The Western lifestyle, which includes a diet low in microbiota-accessible carbohydrates (MACs), has selected for a microbiota with altered membership and functionality compared to those of groups living traditional lifestyles. Interactions between resident microbes and host leading to immune dysregulation may explain several diseases that share inflammation as a common basis. The low-MAC Western diet results in poor production of gut microbiota-generated short-chain fatty acids (SCFAs), which attenuate inflammation through a variety of mechanisms in mouse models. Studies focused on modern and traditional societies, combined with animal models, are needed to characterize the connection between diet, microbiota composition, and function. Differentiating between an optimal microbiota, one that increases disease risk, and one that is causative or potentiates disease will be required to further understand both the etiology and possible treatments for health problems related to microbiota dysbiosis.

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My comment: I’ve written a lot about the health benefits associated with the consumption of dietary fiber here on the blog. I’ve also repeatedly highlighted the fact that the typical Western diet is extremely low in indigestible (to the human host) carbohydrates when compared to the diet of our Paleolithic ancestors, and that even those people who eat a nutrient-dense whole foods diet often take in less than optimal amounts of fiber every day. This paper explains how a low fiber intake affects our immunity and health condition and discusses how we should eat to achieve a diverse, resilient gut microbiota.

8. Natural environments, ancestral diets, and microbial ecology: is there a modern “paleo-deficit disorder”?

Abstract: Famed microbiologist René J. Dubos (1901–1982) was an early pioneer in the developmental origins of health and disease (DOHaD) construct. In the 1960s, he conducted groundbreaking experimental research concerning the ways in which early-life experience with nutrition, microbiota, stress, and other environmental variables could influence later-life health outcomes. He also wrote extensively on potential health consequences of a progressive loss of contact with natural environments (now referred to as green or blue space), arguing that Paleolithic experiences have created needs, particularly in the mental realm, that might not be met in the context of rapid global urbanization. He posited that humans would certainly adapt to modern urban landscapes and high technology, but there might be a toll to be paid in the form of higher psychological distress (symptoms of anxiety and depression) and diminished quality of life. In particular, there might be an erosion of humanness, exemplified by declines in altruism/empathy. Here in the first of a two-part review, we examine contemporary research related to natural environments and question to what extent Dubos might have been correct in some of his 50-year-old assertions.

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My comment: What happens when you put an organism (in this case humans) in an environment for which it is poorly adapted? This is one of the key questions this excellent review paper aims to answer. Unlike most other scientific papers on ancestral health, this review article doesn’t just focus on diet, physical activity, and sleep, but it also delves into many other aspects of the gene-environment mismatch we face in the modern world. I devoted a short post to this research paper a while back. It’s quite long, but definitely worth a read.

9. Origins and evolution of the Western diet: health implications for the 21st century

Abstract: There is growing awareness that the profound changes in the environment (eg, in diet and other lifestyle conditions) that began with the introduction of agriculture and animal husbandry ≈10000 y ago occurred too recently on an evolutionary time scale for the human genome to adjust. In conjunction with this discordance between our ancient, genetically determined biology and the nutritional, cultural, and activity patterns of contemporary Western populations, many of the so-called diseases of civilization have emerged. In particular, food staples and food-processing procedures introduced during the Neolithic and Industrial Periods have fundamentally altered 7 crucial nutritional characteristics of ancestral hominin diets: 1) glycemic load, 2) fatty acid composition, 3) macronutrient composition, 4) micronutrient density, 5) acid-base balance, 6) sodium-potassium ratio, and 7) fiber content. The evolutionary collision of our ancient genome with the nutritional qualities of recently introduced foods may underlie many of the chronic diseases of Western civilization.

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My comment: How has the human diet changes over the last 10.000 years, and how have these changes affected human health? These are the key questions you’ll see answered in this excellent review article by Dr. Loren Cordain. The dietary changes mentioned in this article can largely explain why we now have an epidemic of chronic diseases such as type-2 diabetes, osteoporosis, and heart disease in contemporary, affluent societies. If you’ve been interested in Paleolithic nutrition and ancestral health for some time, chances are you’re already familiar with this paper. However, if you aren’t, I highly recommend checking it out, as the article can give you many clues as to how you should design your own diet in order to achieve good health.

10. Hygiene hypothesis and autoimmune diseases.

Abstract: Throughout the twentieth century, there were striking increases in the incidences of many chronic inflammatory disorders in the rich developed countries. These included autoimmune disorders such as Type 1 diabetes and multiple sclerosis. Although genetics and specific triggering mechanisms such as molecular mimicry and viruses are likely to be involved, the increases have been so rapid that any explanation that omits environmental change is incomplete. This chapter suggests that a series of environmental factors, most of them microbial, have led to a decrease in the efficiency of our immunoregulatory mechanisms because we are in a state of evolved dependence on organisms with which we co-evolved (and that had to be tolerated) as inducers of immunoregulatory circuits. These organisms (“Old Friends”) are depleted from the modern urban environment. Rather than considering fetal programming by maternal microbial exposures, neonatal programming, the hygiene hypothesis, gut microbiota, and diet as separate and competing hypotheses, I attempt here to integrate these ideas under a single umbrella concept that can provide the missing immunoregulatory environmental factor that is needed to explain the recent increases in autoimmune disease.

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My comment: Humans’ microbial environment has changed dramatically over the last 10.000 years. By moving into closed buildings and disconnecting ourselves from the natural environment we’ve lost touch with some old microbial friends that have co-evolved with us for millions of years. As I’ve highlighted many time on the blog, these alterations of our microbial landscape have contributed to the rapid rise in autoimmune conditions and inflammatory disorders in industrialized nations. Graham Rook, the author of the paper above, is an expert on the role microorganisms play in human health and has written several scientific articles on topics such as the old-friends hypothesis, immunoregulation, and the hygiene hypothesis.

That’s it for today’s post. I hope you found something interesting. Let me know in the comment section if you have any questions or comments and/or if you have any additions to the list.

Comments

  1. It may help people new to Spreadbury’s ideas if they watched this short video of him summarizing his hypothesis.
    https://www.dropbox.com/s/b6ruqe0dfej8ab8/spreadbury3.mp4?dl=0

  2. Thanks, Eirik. I’ve not yet read these papers but plan to delve into them.

    Regarding gut microbiome, appropriate carbohydrates, etc., I am wondering what your opinion is of juicing. I have a couple of friends who swear by it, and I have to admit they have lost weight and look healthier. In case you’re unfamiliar with the term, I’m talking about running a large batch of fresh veggies through a juicer and drinking the resulting liquid. The theory behind this idea, apparently, is that it provides more nutrients than eating whole vegetables, but most of the fiber gets thrown out as “waste.” Juicing is both labor intensive and expensive. Is it worth the effort?

    Alternatively, what about powdered green drinks? There are dozens of them on the shelves and available online. They all taste terrible but are touted to be loaded with vitamins and minerals. Are they really, or is this mostly marketing hype?

    • Hi Shary!

      I don’t recommend juicing. You’re much better off eating (and actually chewing) whole vegetables. If you juice the veggies and throw out most of the fiber, you’re basically removing one of the key health-promoting components of the plant. The glycemic index of the food increases, you won’t feel as satiated after the meal, and your gut bacteria won’t get anything for dinner.

      Also, the actual process of chewing is far more important than most people realise. The digestion of food begins in the mouth! In other words, I highly recommend that you chew your food rather than drink it. Keep in mind, food processors and jucing machines are very recent innovations. Our primal ancestors “ate” their food, they didn’t drink it.

      You should also stay clear of powdered green drinks. Stick to real food 🙂

  3. Ian Spreadbury is a really brilliant researcher and his paper is truly amazing.
    These papers together with the evolutionary theory and epidemiological evidence, enlight with very low shadow of doubt that neolithic and far more industrial food, lifestyle disconnected from Nature and our habitat, are actually the trigger of almost all the degenerative diseases.
    I’m really disappointed that some Paleo advocates only rely on Weston Price’s book Though it’s really useful and enlightening, it has some shades of gray. They use it to push dairy claiming that some cultures were healthy while consuming dairy and grains. First of all Price took just some pictures and data of teeth health. The problem is that though a bad oral health is linked to a poor overall health, it may be possible that a not optimal health doesn’t translate in an apparent oral issue. More reliable and longer studies involving health markers have been done on Kitavans, Aborigins and some others it’s better off to rely on these, together with animal studies, rct etc…
    The picture took from Price, though interesting and toward the right direction, may be in some way misleading.
    Advocates of dairy use this book to push dairy consumption without any or at least very few other clues about its safety and instead with many issues about its hazard.

  4. Hi Eirik,

    Is fructose from a fresh whole fruit cellular or acellular?

    Is a fresh fruit heavy diet detrimental?

    I’ve noticed that horticulturalists aside, the diet of most foragers consists of little vegetables. The hadza for example eat baobab fruit, berries but no non starchy vegetables.

    What are your thoughts?

    • Hi Sam.

      Is fructose from a fresh whole fruit cellular or acellular?

      The carbohydrate in fruit is not of the acellular type.

      Is a fresh fruit heavy diet detrimental?

      I would not recommend that you eat a diet that is very high in fruit, in part because the fruit you’ll find at the grocery store tends to be markedly higher in sugar and lower in fiber than their wild counterparts.

      That being said, fresh fruit can certainly be a part of your diet. Personally, I tend to stick to fruit that’s fairly low in fructose and high in fiber (e.g., slightly green bananas).

      I’ve noticed that horticulturalists aside, the diet of most foragers consists of little vegetables. The hadza for example eat baobab fruit, berries but no non starchy vegetables.

      What are your thoughts?

      Great question, which hits on a topic I’d like to do an article on in the future.

      When foragers go out hunting and gathering, they’re generally looking to maximize the number of calories they get for the amount of energy they put in (optimal foraging theory). “The most bang for the buck”. In other words, they prefer foods that have a fairly high calorie density (e.g., honey, meat) over low-calorie plant foods. Hunter-gatherers don’t sit around eating lettuce and cabbage all day long. Rather, they mostly eat meat, fruits (e.g., the baobab fruit you mention), honey, and/or tubers.

      Does that mean we should do the same? Not necessarily. As mentioned, the root vegetables and fruits we eat today tend to be lower in fiber and higher in sugar than the ones hunter-gatherers eat. Non-starchy veggies provide fiber, as well as food-borne bacteria that may help increase the diversity of your gut microbiome.

      I have many more thoughts on this topic, but I’l leave it there for now.

      Let me know if you have any further questions.

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