Reference topic 37: The Individual Variable
Lactose intolerance and evolution: genes tuned to diet and place
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In 2017 a team of physiologists reported what they had measured at Everest Base Camp, 5,300 meters (17,400 feet) up the mountain. They had set the working muscle of 15 Sherpas beside that of 10 lowlanders who had climbed to the same camp.1
The results ran against intuition. Sherpa muscle was worse at one thing: burning fat for fuel. At everything else that matters in thin air, it was better. It used oxygen more efficiently, handled energy more cleanly and showed less oxidative stress, the wear that reactive oxygen does to cells. The difference tracked a variant in PPARA, one of the genes that sets which fuel a muscle reaches for.1 No amount of training would have closed that gap for the visitors. It lay in how the machinery had been built, not in how hard it had been worked.
Mismatch card
- The system
Local genetic adaptation: the regional tuning of digestion, metabolism, blood and breath laid down over the last few thousand years.
- What it expects
The diet, altitude, sunlight and pathogens of the place where your recent ancestors lived and reproduced.
- What it gets
Global food supply, air travel, latitude changes within a single lifetime, and a consumer test that reports ancestry as if it reported physiology.
- What happens in the gap
Mostly small mismatches (the dairy that disagrees, the flush after one glass), occasionally serious ones (sickle trait far from malaria, vitamin D deficiency far from the equator), and a steady traffic in genetic advice that outruns the evidence.
- The handrail
Test the few traits that are genuinely actionable, respect the alcohol flush, match vitamin D to skin and latitude, and acclimatize on the mountain's schedule (●●○)
- Strength of evidence
●●● The adaptations themselves are replicated, well-mapped findings; the weak link is any attempt to turn an ancestry report into individual advice (●○○).
What this topic covers
- ·Three Mountains, Three Answers
- ·The Milk That Came Before the Gene
- ·Bread, Wine and a Bitter Leaf
- ·Fat, Blood and Breath
- ·The Ghost in the Mosaic
- ·What a Test Can and Cannot Tell You
The practical version is in the book: Chapter 2, What Your Body Expects, and How to Trust This Book.
The handrail
Topics 40 to 42 hold the general programs. These four items are the ones ancestry actually changes.
Each recommendation carries the strength of the evidence behind it. How the grades work.
Settle the dairy question by trial, not by haplogroup
StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.If milk reliably brings bloating, gas or cramping, the likely explanation is lactase non-persistence, the default state for most of the world's adults. Two weeks of lactose-free dairy or a lactase enzyme taken with dairy, followed by a deliberate re-challenge, answers it cheaply; a clinician can confirm with genetic or breath testing. Fermented dairy is often tolerated when milk is not. Persistent gut symptoms still deserve a doctor's attention, since celiac disease and inflammatory bowel disease can imitate this.
Treat the alcohol flush as information
ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.Facial flushing, racing heart or nausea after a drink, most common in people of East Asian descent, signals reduced ALDH2 activity and, with continued drinking, substantially raised risk of esophageal cancer.13 The useful response is to drink less or not at all. Do not suppress the flush with antihistamines, antacids or products marketed for the purpose: that removes the warning while leaving the acetaldehyde exposure untouched.
Match vitamin D to skin and latitude
ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.How much vitamin D your skin makes from a given dose of sun depends on its pigment and on your distance from the equator. Topic 19 carries the doses, the trial evidence and the cautions.
Climb slowly whatever your ancestry
ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.The standard rules of high-altitude travel apply to everyone: ascend gradually, allow rest days, learn the symptoms of acute mountain sickness, and descend if they worsen. The adaptations in this chapter shift population averages; they exempt no individual from the ascent-rate guidance. This is a safety matter, not a comfort one: acute mountain sickness can progress to high-altitude pulmonary or cerebral edema, both of which can kill.
The skeptic's corner
The case against this topic, from the research itself.
Every finding in this chapter describes groups and odds; none of them predicts an individual. Someone with plenty of ancestry from a lactase-persistent population can still be lactose intolerant. Someone with no Tibetan variants can acclimatize to altitude over days to weeks by ordinary routes. The book's thesis, that the environment is the intervention, works inside ranges shaped by genes, not in spite of them.
The single-gene stories here make a compelling chapter, and an unrepresentative one. The lactase, alcohol-flush, sickle-cell and Tibetan altitude genes are unusually clean exceptions with large effects. Most chronic disease risk is polygenic: spread across hundreds or thousands of variants of tiny effect, and heavily shaped by environment. A polygenic risk score, which adds those small effects together, shifts a probability; it does not diagnose. Worse for anyone hoping to use one, these scores are built from study groups that skew heavily European. They typically work less well in people whose ancestry is scarce in the data they were built from.
Finally, the labels. "European," "East Asian" and their cousins run through the genetics literature, including papers cited above, as conveniences built from wherever the samples came from. Human genetic variation mostly shifts gradually from place to place, and mixing between groups is the historical norm. The categories help describe how common a variant is. They mislead when used to describe people.
Terms this topic defines
Related topics
Sources cited above
- 1.Horscroft, J.A., Kotwica, A.O., Laner, V., West, J.A., et al. (2017). "Metabolic basis to Sherpa altitude adaptation." Proceedings of the National Academy of Sciences, 114(24), 6382-6387. https://doi.org/10.1073/pnas.1700527114. 15 Sherpas and 10 lowlanders studied at Everest Base Camp (5,300 m); Sherpa muscle showed lower fatty-acid oxidation capacity, more efficient oxygen use, better energetics and less oxidative stress, linked to a PPARA variant.
- 2.Beall, C.M. (2007). "Two routes to functional adaptation: Tibetan and Andean high-altitude natives." Proceedings of the National Academy of Sciences, 104(Suppl 1), 8655-8660. https://doi.org/10.1073/pnas.0701985104. A comparative review.
- 3.Alkorta-Aranburu, G., Beall, C.M., Witonsky, D.B., Gebremedhin, A., Pritchard, J.K., and Di Rienzo, A. (2012). "The genetic architecture of adaptations to high altitude in Ethiopia." PLoS Genetics, 8(12), e1003110. https://doi.org/10.1371/journal.pgen.1003110
- 13.Brooks, P.J., Enoch, M.A., Goldman, D., Li, T.K., and Yokoyama, A. (2009). "The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption." PLoS Medicine, 6(3), e1000050. https://doi.org/10.1371/journal.pmed.1000050. This review does not give a single continent-wide carrier percentage; the first edition's "roughly 36% of East Asian populations" is not supported by it and has been removed. (the inactivating ALDH2 variant is known as rs671)
This topic carries 21 notes in the research manuscript; the 4 above are those behind the material on this page. Full source register.