Paleodiet or Paleodelusion?


It is thought that much human evolution occurred during the Pleistocene – 2.8 million to 12 thousand years ago. What are the consequences of genes optimized for a Pleistocene environment now expressed in the modern environment? We have new technology, petro-chemicals, artificial light, recreational drugs. In particular, we consume radically different food than our predecessors. Are we healthier if we eat like we did in the Pleistocene?


Pleistocene scene

This thinking has led to a Paleo lifestyle movement that advocates for a Paleo diet. This concept has become popular in part because it prioritizes eating meat and some high fat foods. But is this really the healthiest option, and the best evolutionary insight as to what we should be eating? What exactly is the Paleo diet, and how much should we worry about eating only foods that we were evolved to eat?


The Paleo diet raises additional questions. There is tremendous diversity in modern human diets, even among traditional human populations.  Which stone age populations should we emulate? Can we really know how our Pleistocene ancestors ate with any certainty? How far back should we go – 1,000 years, 10,000 years, 100,000 years -to pinpoint the healthiest evolved diet for humans? Can modern hunter-gatherers, like the Hadza of Tanzania be a stand-in for our ancestral hominins in terms of diet?

Hadza and honey

Hadza consuming honeycomb

[Students – check back this weekend for journal club assignments. You will be expected to present your journal club critiques on October 4th to give you sufficient time. We will be discussing Paleo diets on September 27th]

1)  Eaton (2006)-Ancestral human diet

2) Paleofantasy by Marlene Zuk

3) Genne-Bacon Thinking evolutionarily about obesity.

4) Paleo microbiota

Assignment due September 27th: Of the different sources of animal protein, fish seems to be very healthy, maybe even the healthiest, in the human diet. Elaine Morgan, an Oxford trained anthropologist, argues that early humans had an aquatic phase – the so called “aquatic ape” hypothesis, first proposed by marine biologist Alister Hardy. Morgan, Hardy, and others propose that early aquatic humans spent a lot of time in the water, explaining our lack of hair and tails, the ability to hold our breath, our upright posture good for wading, and our air filled sinuses. Aquatic apes would have eaten a lot of seafood, rich in omega-3 fatty acids, useful in brain development, maybe even permitting humans to evolve large brains. Argue for or against the idea that an aquatic phase for humanity explains why fish, and marine omega-3 fatty acids, are healthy for us humans.

Useful links:

“We got smart from eating fish and living in water”- Japan Times

Aquatic explanation for the sinuses

Wired magazine Sorry David Attenborough

Aquarboreal ancestors

John Hawks on the Aquatic Ape Hypothesis

Fever and sepsis – host defenses and new normals

When to treat and when to leave alone…

In this week’s class, we will explore the idea of normal in medicine. What is normal? Can the concept of adaptation help guide what to do with an “abnormal finding”? We confront these questions all the time in the hospital. Now it is your turn to weigh in.

Lets start with a patient case: He is 48 years old, with a history of alcohol abuse, and a fever for 2 days. He has been coughing with grey sputum and bloody streaks for the last 24 hours. Increasingly short of breath, he calls 911 and is brought to the emergency department.

His chest x-ray looks like this:

Left lower lobe pneumonia

His temperature is 40°C.  Anything above 38°C (100.4 °F) is considered a fever.

Blood cultures are drawn and antibiotics given. He is transferred to the ICU because his oxygen levels and blood pressure continue to drop. In the ICU, his doctor diagnoses him with septic shock. She also orders a dose of acetaminophen (also known as tylenol or paracetamol) to reduce the fever. Medications like tylenol that reduce fever are known as antipyretics, and are commonly prescribed for febrile patients in and out of the hospital.

Is it a good idea to reduce the fever?

Evidence from animal studies support the view that fever is beneficial (read the abstracts in the links in this section). Matthew Kluger back in the early 1970s showed that a behavioral fever was critical in keeping lizards alive after experimental infection with gram-negative bacteria. Kluger subsequently showed that fever improves bacterial killing by immune cells.

One relevant fact, arguing for the evolution  of fever, is the fact that it exists in a wide variety of organisms, as reviewed here. Even some invertebrate organisms exhibit a behavioral fever, including grasshoppers, honeybees and snails.  Animal studies suggest that antipyretic use (aspirin) increases mortality from Streptococcus pneumoniae infection With these lines of evidence, you would think that we should certainly not treat fever with tylenol. But we still do, all the time. The human data is not as clear as the animal studies.

Young and Saxena wrote in the journal Critical Care on fever and its treatment:

“arguments based on the evolutionary importance of the febrile response do not necessarily apply to critically ill patients who are, by definition, supported beyond the limits of normal physiological homeostasis. Humans are not adapted to critical illness.

This logic was expressed by Foddy (2012) who wrote: “The argument from evolution assumes some degree of continuity in environmental circumstances, but at present there are strong discontinuities in the structure of our world. Given these changes, it would be foolish to place too much trust in the adaptive quality of traits that evolved across aeons of nomadic hunting and gathering.”

On the other hand, consider the argument from Fukuyama (2002) who wrote:

“There are good prudential reasons to defer to the natural order of things and not to think that human beings can easily improve on it through causal intervention. This has proven true with regard to the environment: ecosystems are interconnected wholes whose complexity we frequently don’t understand, building a dam or introducing a plant monoculture into an area disrupts unseen relationships and destroys the system’s balance in totally unanticipated ways. So too with human nature … doing nature one better isn’t always that easy, evolution may be a blind process, but it follows a ruthless adaptive logic that makes organisms fit for their environments.”

Depending on your point of view, fever might or might not be adaptive for our sickest patients.   We will discuss whether evolution and adaptation is irrelevant for ICU patients who are closest to death.

Listen to this excellent talk by an expert on fever:

Paul Young’s evolution-minded lecture on the function of fever and the HEAT trial, a large randomized controlled trial of antipyretics.

Fast forward to minute 3:48 for the good stuff.

Reading 1 Matthew Kluger’s review on fever: The Adaptive Value of Fever

Reading 2 (read the abstract and conclusions)  Young The Heat Trial NEJM

Reading 3 Smoke Detector Principle -Nesse

Listen also to the EvolutionMedicine podcast #2 (July 4, 2016)

Writing assignment:

A start-up biotechnology company has come out with a novel long-acting fever reducing drug. Instead of lasting 4 hours like acetaminophen (Tylenol) and ibuprofen (Motrin), the new drug Qoolaid lasts much longer. A single dose of Qoolaid reduces body temperature and prevents fever for 2 weeks. The company executives are excited to report that because Qoolaid also has a rapid onset of action, reducing body temperature after only 90 seconds, it will provide comfort to patients with a wide range of infections. Wall Street is anticipating that the public stock offering of this “blockbuster” drug will bring in millions of dollars. Should you invest in Qoolaid? Why or why not?


Microbes, Mental Health. and Zombies

Are we masters of our own fate… or have our brains been zombified by microbes?

Cordyceps fungus takes over the brains of ant hosts

Cordyceps fungus takes over the brains of ant hosts. Infected ants that usually inhabit the ground are manipulated by the fungus – they climb tall vegetation where a fruiting body of the fungus emerges from their heads.

To learn more about Cordyceps and similar mind-controlling parasites, watch Zombie parasites on YouTube.

Dethlefson and colleagues wrote that “from the microbial perspective…the distinction between human health and disease is important only as far as it affects microbial fitness.

This raises the possibility that microbes manipulate us for their own benefit. Examples abound of parasites like Cordyceps exploiting their insect hosts. But do microbial parasites affect us humans in the same way?

Dethlefson and colleagues write that microbiota are “prevented (usually) from exploiting the host to obtain additional resources,” citing the immune system as “the most conspicuous set of anti-exploitation adaptations involved in human–microbial symbiosis.”

The red queen effect

The red queen effect

The fact that we need immune “anti-exploitation” adaptations is a clue that we are engaged in a never-ending arms with harmful microorganisms.

But the immune system only gets us so far. For example, infection by the protozoan Toxoplasmosis provides an excellent example of a parasite that manipulates the brain and behavior of mammals that it infects. Infected rabbits for instance lose their innate fear of bobcat urine. Rabbits that are attracted to feline predators have a distinct disadvantage when it comes to fitness. Not so for the parasite. It’s fitness is increased as it completes its life cycle. Our closest relative, the chimpanzee, also seeks out the urine of their main predators, leopards, when infected by Toxo. In the United States, almost a quarter of human adults are infected with Toxoplasmosis. Problem? Perhaps.

Leopard pee – attractive to infected Toxo-infected Chimps

How about our microbiomes, the complex microbial communities that mainly inhabit our guts? Are they exploiting our brains and behaviors? Indeed, microbes are suspected to be involved in depression and anxiety, demonstrated experimentally in mice. Is this manipulation?

Marble burying anxious mice

Marble burying anxious mice

Bruce-Keller (2015) and colleagues showed that the microbiome is responsible for marble burying behavior in mice that were fed a high fat diet (HFD). Anxious mice like to bury marbles. The implication of this study is that microbes can make mice anxious and depressed.

Does this mean that microbes cause depression in people? Drawing on these kinds of studies, investigators have given probiotic microbes to people with depression. They seemed to get better!

Depression score was lower in patients treated with Lactobacillus.Akkesheh Nutrition 32 (2016) 315–320 (Beckwith Depression Inventory)

Depression score was lower in patients treated with Lactobacillus.

Akkesheh and colleagues gave  Lactobacillus acidophilus and Lactobacillus casei and Bifdobacteria to depressed patients in Iran. Probiotics apparently made patients less depressed. (The dark blue bar indicates placebo, and the light blue bar indicates the probiotic group. They used the Beckwith Depression Inventory to measure depression.)

How might toxoplasmosis affect chimp brains? How does Lactobacillus brighten mood? We don’t know, but there are clues.

Bacteria make neurotransmitters – the same ones that we use:

Lyte PharmaNutrition 2013

Lyte PharmaNutrition 2013

Presumably bacteria evolved the signaling molecules like GABA, norepinephrine, and serotonin first. We eukaryotes might have evolved nervous systems using the same molecules because they conveyed useful information about the doings of microbes (but who knows.)



My research collaborators proposed that gut microbes might affect what we decide to eat.


1) How Pernicious Parasites Turn Victims into Zombies.

“Joanne Webster and colleagues from Imperial College, UK, and the University of Leeds, UK, make the case that Toxoplasma may be a contributory factor in some cases of human schizophrenia given its presence in the brains of infected individuals and our long lifespan”

2) Alcock J, Maley C, Aktipis A. (2014) Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms. Bioessays.

” Like microscopic puppetmasters, microbes may control the eating behavior of hosts through a number of potential mechanisms, including reward pathways, production of toxins that affect mood, and hijacking of neurotransmitters via the vagus nerve”

3)  Melancholic Microbes: a link between gut microbiota and depression?

“Whether fecal transplantation of microbiota from animals or other models of depression could also alter behavior of the recipient is an intriguing possibility”

4) Sutterland_Toxoplasmosis gondii in schizophrenia, bipolar disorder and addiction

“A significant OR of 1.91 (95% CI 1.49–2.44, P < 0.00001) was found, indicating an increased prevalence of T. gondii infection in heroin addiction”

Writing for next Tuesday, September 13th (pick one):

  1. Anxiety and depression often go together. Some people think that anxiety and depression might be adaptive (beneficial) for the patient. Do you? What do you think about this hypothesis: anxiety and depression might be adaptive for microbes and harmful for humans?
  2. Suppose you want to test the hypothesis that food cravings are caused by manipulative gut microbiota? What is the best way to do this?

High Altitude Evolution and podcast

Hypoxia on Cotopaxi

I took the above photo from 18,700 feet near the summit of Cotopaxi, an (active) volcano in the Ecuadorean Andes. We were suffering from a bit of exertional and hypoxic stress in this photo. On the other hand, native people of the Andes can cope with hypoxia at altitude better than us genetic lowlanders. How is this so? The evolutionary biology of high altitude peoples of the Andes, Himalayas, and Ethiopian Plateau is the topic for September 6th.

This week’s EvolutionMedicine podcast “Altitude Adaptation and Maladaptation” is here (optional):

Screen Shot 2016-09-02 at 11.36.33 AM

A pattern often seen is that blood hemoglobin increases with higher altitude of residence

We will explore the different routes to physiologic adaptation to altitude in Tuesday’s class.

For discussion: How might gene-environment mismatch account for acute mountain sickness in Europeans? How many generations does it take to evolve solutions to the problem of living in a high altitude environment?

Writing project: Why do the three major high altitude groups each have different adaptations to altitude?

Readings (updated):

1. Beall An Ethiopian pattern of human adaptation to high-altitude hypoxia

“The results of this study suggest that Ethiopian high-altitude natives respond to hypobaric hypoxia differently than Andean or Tibetan highlanders.” p. 17218 Beall 2002

2. Storz Genes at High Altitude

“Andean residents at high altitude are also characterized by an elevated hemoglobin concentration. By contrast, Tibetans living at elevations of up to 4000 m present a hematological profile similar to what would be expected at sea level.” p. 40 Storz 2010.

3. National Geographic: Three high altitude people

Despite living at elevations wih low oxygen content, “the Ethiopian highlanders were hardly hypoxic at all,” Beall said. “I was genuinely surprised.” p. 2 NatGeo

4. Two routes to functional adaptation: Tibetan and Andean high-altitude natives Beall-2007

“High-altitude hypoxia may be an even stronger agent of natural selection than falciparum malaria.” p. 8659. Beall 2007.

Extra readings:

Beall Tibetan and Andean Patterns of Adaptation to High-Altitude Hypoxia

“Tibetan resting ventilation was roughly 50% higher than Amarya resting ventilation. For example male Tibetans had an average resting ventilation of 19.7 l/min compared to an average of 13.4 for male Amayra”  p. 204 Beall 2000

Biello How Tibetans enjoy the high life

Xing Adaptation and Maladaptation to Ambient Hypoxia: Andean Ethiopian, and Himalayan Patterns.

Mentioned in the podcast:

Outside magazine: Alex Lowe’s body found on Shishapangma

Aging and menopause

Spawn till you die by Ray Troll

Listen to this audio link by the Canadian born rapper Baba Brinkman: all the way to senescence (with lyrics):

Understanding age-related risk of death and age-related disease are the result of tradeoffs and occur because of evolved life history traits.

We are going to cover evolutionary hypotheses of senescence for next week’s class. These hypotheses include antagonistic pleiotropy, declining power of selection, and the disposable soma hypothesis.

Antagonistic pleiotropy is the concept that a gene for survival or a gene that promotes
reproduction early can be selected for even if it kills you at a later
age. So selection favors juvenile survival at the expense of old age survival. This hypothesis recognizes that most traits have both costs and benefits, and are tradeoffs. The tradeoff in antagonistic pleiotropy is improved health and fertility in the young, but disease and premature death in older individuals.

Haldane and Medawar proposed the declining power of selection hypothesis of aging. This proposes that genes for maintenance and repair of the body are selected for more strongly at early ages (pre-reproduction) than after reproductive age. For this: imagine a hypothetical gene that prevents cancer at age 10 and another gene that prevents cancer at age 100. The gene that prevents cancer at age 100 will not have any effect most of the time because most people are dead by age 100 (this remains true even if you take senescence out of the equation – random accidents will claim many lives). The gene that affects 10 year olds is more likely to be expressed and have a benefit simply because most people are alive at age 10. Therefore the old-age gene will be invisible to natural selection, the gene that affects 10 year old will be subject to positive selection.

Medawar extended his idea to include mutation accumulation. This idea posits that the body accumulates deleterious mutations that take effect at older ages. Because of the declining power of selection, these mutations are not selected against, and contribute to declining function that we see with aging. In wild populations, not enough organisms reach advanced age, so these mutations are invisible. If allowed to achieve advanced chronological age, these mutations exert damaging effects, reducing fitness and contributing to senescence.

The disposable soma hypothesis is another idea to explain aging. This hypothesis recognizes that the nonreproductive part of the body (the soma) exists only to support the reproductive part of the body. At any moment in time an adult can devote energy to the maintenance of the body or to reproduction. Put simply, after successful reproduction, the soma is “disposable”, and genes are passed on. This tradeoff is vividly illustrated in adult salmon, also in octopus, which appear to do all their aging at once, immediately after a single reproductive effort. In many animals, bearing offspring shortens lifespan. There is some evidence of this in humans too.


Menopause is a strange phenomenon, because it represents premature aging of the female reproductive organs, asynchronous with the rate of decline in function for the rest of the body. It is paradoxical because it would seem that natural selection would seem to favor maximal personal reproduction throughout a woman’s adult life. Given the fitness benefits of continued reproduction, why does the female reproductive organ – the ovary – quit working so early? Humans are nearly unique in having a menopause; although menopause is also reported in killer whales.

Some suggest that menopause evolved because grandmothers are more successful at passing on their genes by investing in grandchildren than in more babies of their own. Others argue that menopause is a consequence of modern medicine prolonging the lifespan. This artificial lifespan prolongation hypothesis proposes that most pre-historic women would be dead by 60 in the environment of evolutionary adaptedness (EEA). So for ancient women, reproductive aging might have been in sync with aging of the rest of the body. In this view menopause is a gene-environment mismatch.

Writing assignment: What best accounts for menopause in humans –  the grandmother hypothesis, the artificial lifespan prolongation hypothesis, something else?

Readings for next week:

1.  Still Pondering an Age-Old-Question. Flatt T and Promislow EL. 2007. Science (318) 1255-1256.

2. Fabian, D. & Flatt, T. (2011) The Evolution of Aging. Nature Education Knowledge 3(10):9

3. Why do we age? Kirkwood Austad Nature 2000  (focus on section on reproduction and menopause)

4. Hawkes K. Human longevity: the grandmother effect

5. Lemaitre 2015. Early-late life tradeoffs and the evolution of aging in the wild

This piece about the death habits of female octopus is also very cool and worth a read.


2016 Evolutionary Medicine Course

Screen Shot 2016-08-22 at 1.40.55 PM

The 2016 UNM Evolutionary Medicine course starts tomorrow, August 23rd, 2016!

Starting tomorrow, we will peel away conventional preconceptions about health and disease, using the lens of evolution to better understand our humanity and our well-being.

Students will learn:

  1. Amazing case studies that show why evolution matters to real patients.
  2. Cutting edge topics from expert guest lecturers in evolutionary medicine.
  3. Why evolution is indispensable for physicians and biomedical researchers.
  4. How we evolved with the human microbiome, with far-reaching consequences.
  5. And much more!

Teaching evolutionary medicine, podcasted:

Check the syllabus here.

Students: please read the following before class tomorrow:

1. Alcock and Schwartz 2011 A clinical perspective in Evolutionary Medicine: What we wish we had learned in medical school. Evolution: Education and Outreach, 2011.

2. Stearns . Evolutionary Medicine: Its Scope, Interest, and Potential. Proceedings of the Royal Society B, 2013.

Optional, but please read if you have time:

  1. Rook.  2010. Clin Exp Immun 160: 70–79. (see emailed document)
  2. Stein et al. Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children N Engl J Med 2016; 375:411-421.

The holobiont

Fitness InterestsAre we a mammal-microbial collective? Should we think of our interaction with our resident microbes as a harmonious, mutually helpful partnership, or a relationship gone sour?  In this podcast, I will lay out my case for why I think the (mutualistic) holobiont concept is often wrong headed and misleading.

Here is EvolutionMedicine ‘cast #6 for August 15th, ‘The Holobiont’:


Before proceeding further, let me first express my admiration for the point of view laid out in the recent paper “Getting the hologenome concept right, an eco-evolutionary framework for hosts and their microbiomes” (Theis et al. 2016).” My views align pretty well with the latter part of this paragraph:

“In The Hologenome Concept, some of us stated that “evolution of animals and plants was driven primarily by natural selection for cooperation between and with microorganisms” (Rosenberg and Zilber-Rosenberg  2013) while in other venues the concept “places as much emphasis on cooperation as on competition” (Rosenberg and Zilber-Rosenberg  2009) This latter statement is more precisely aligned with the pluralistic nature of the holobiont, namely that “natural selection…on holobiont phenotypes…can work to remove deleterious nuclear mutations or microbes while spreading advantageous nuclear mutations or microbes” (Bordenstein and Theis 2015). In fact, some of us argued that conflicts of interests resulting from the nature of the transmission of microbes to the next host could select for microbes that can manipulate the biology of their host to improve their own transmission (Dheilly et al. 2015)”

By contrast, Michael Shapira in a recent paper published in Trends in Ecology and Evolution argues that cooperation is the key to co-evolution of the host-microbiota collective. He writes: “overall, host–microbiota interactions describe a mutualistic symbiosis.”

I disagree.

It is this version of the holobiont point of view that I take issue with: natural selection for cooperation as a primary driver of the evolution of animals and plants. Instead my coauthors and I have argued that conflict is a more important driver.

Evidence for cooperation is exciting, fascinating, and necessary for the complete story of human-microbial association. But, these mutualistic interactions are not the most interesting or important, because they often fail to explain why diseases occur.

Mutualism is but one outcome of evolution acting on host and microbiome. Competition and conflict are equally likely, as we have argued here and here.

In diseases states,  our partnership with microbes is like a bad relationship:

Microbes consume you. They eat your lunch. And they invade your personal space.


Microbiome: collection of microbial genes in a host or other defined environment.

Microbiota: the collection of microorganisms resident in a host (or other environment).

Holobionts: the combined organism, made up of host & microbiota.

Hologenome: the combined host and microbial genes of a holobiont that may constitute a distinct and useful unit of selection that drives co-evolution.



Copyright © Joe Alcock MD