Are Humans Designed for Radical Diet Shifts?

Early human migration around the globe required that they adapt to available food sources. Such adaptability entails that the human digestive tract can tolerate temporary radical diet shifts, including intermittent high-fat intakes. New discoveries appear to affirm this feature and how it reflects planned design.

Mammal Dietary Needs
Mammals are the most amazingly designed of Earth’s creatures. Their warm-blooded circulatory system allows them to function at high levels for sustained periods. This capability, however, requires that they maintain a high and sustained caloric and nutritional intake. For most mammals, such food requirements make it impossible for them to depend upon a single set of food sources. They need to adapt to radical diet shifts and do so quickly.

Among large mammals, the one with the highest caloric and nutritional intake needed per pound of body weight is Homo sapiens sapiens—modern humans. Humans especially need diet flexibility and adaptability.

Mice and rats possess a digestive tract that closely matches that of humans. For this reason, researchers study them to learn how diet changes can affect humans. A team of seven researchers led by Jacob Enriquez performed a set of diet change experiments on mice to determine how well their intestines can adapt to a rapid and radical change in their diet.1

Diet Change Experimental Results
Enriquez’s team fed adult wild-type mice a balanced diet that consisted of 13% fat, 58% carbohydrate, and 29% protein for a period of several weeks. They then replaced this balanced diet with a high-fat diet (HFD) consisting of 60% fat, 20% carbohydrate, and 20% protein designed to simulate wild field mice running out of their normal diet and opportunistically discovering a source of animal fat. The team analyzed the inner linings of the mouse intestinal tracts, the oxygen consumption, and the carbon dioxide exhalation. Within 24 hours of the shift to an HFD, they observed several changes. In the first, the mice underwent a dramatic whole-body metabolic change, intestinal crypt-niche (a gland) stress, and an inflammatory response of intestinal Paneth cells (important in immunity). While the team could not rule out other related changes in the mice’s intestines, they did note that there was no measurable change in the intestinal surface area after one week of a continual HFD.

Second, in addition to the metabolic and intestinal changes, Enriquez’s team observed an upregulation in at least six genes associated with cellular stress after just one day from the switch to an HFD. This enhanced gene expression affected the operation of cells lining the interior of the mice’s intestines such that the capability of absorbing fatty acids was markedly increased.

After three days on an HFD, the mice displayed a much higher rate of lipid uptake. This greater uptake correlated with an observed increase in the expression of lipid transporter genes. From the first day on an HFD the mice had an increased intake of calories. Even after just one day on an HFD the mice displayed weight gain. This weight gain continued with every extra day on the HFD.

A third immediate change brought on by the switch to an HFD that Enriquez’s team observed was an increase in the prevalence of the gut microbiome. Previous studies had shown that exposure to an HFD altered the microbial diversity in the microbiome for both mice and humans.2 This increased prevalence and species alteration in the gut microbiome greatly enhanced the digestion efficiency of short-chain fatty acids.3

Previous diet experiments show that a sustained daily HFD has harmful consequences for animals.4 Animals become obese, lose muscle-skeletal force, and show a marked increase in metabolic diseases, especially insulin resistance, ketogenesis, and hepatic steatosis. The outcomes are even more harmful for animals on a sustained high-fat, high-sugar diet.

Diet Change Implications
The metabolic and health changes induced by switching from a balanced diet to an HFD observed by Enriquez’s team and other research teams in mice and rats have implications for humans. The digestive tract of mice and rats is an excellent proxy for the human digestive tract. Based on an analysis of 27 published dietary studies, a team led by Jordan Bisanz established that “a machine-learning approach defined a signature that predicts the dietary intake of mice and demonstrated that phylogenetic and gene-centric transformations of this model can be translated to humans.”5 Another study of men with a sedentary lifestyle showed that even a short-term consumption of an HFD impairs both whole-body efficiency and cognitive function.6

Some carnivorous mammals survive on an HFD, but they do so intermittently. That is, rather than consuming high-fat meals on a daily basis, they typically spread such meals out by days and even weeks. Also, some herbivores and omnivores opportunistically find high-fat meals, but these opportunities are rare and typically spread out by weeks and months. Only humans, and the domesticated animals that they feed, have the luxury of a sustained HFD where they consume high-fat meals on a daily basis.

These research studies establish that mammals are amazingly designed to efficiently and safely take advantage of occasional high-fat meals. In particular, the digestive tracts and genomes of rodents and humans are designed to rapidly and efficiently respond to the opportunity of a high-fat meal. Problems arise only when an HFD is sustained. For humans, those problems bring on serious health issues. Good human health requires a sustained, balanced diet where only occasional, brief interruptions with an HFD are tolerated. In this way, the human digestive tract appears intentionally designed to exploit occasional periods of high-fat intake while moving into new ecosystems or undertaking temporary high-energy demanding activities like mountain climbing or traversing winter terrain.


  1. Jacob R. Enriquez et al., “A Dietary Change to a High-Fat Diet Initiates a Rapid Adaptation of the Intestine,” Cell Reports 41, no. 7 (November 15, 2022): id.111641, doi:10.1016/j.celrep.2022.111641.
  2. Jordan E. Bisanz et al., “Meta-Analysis Reveals Reproducible Gut Microbiome Alterations in Response to a High-Fat Diet,” Cell Host & Microbe 26, no. 2 (August 14, 2019): 265–272, e4, doi:10. 1016/j.chom.2019.06.013; Lawrence A. David et al., “Diet Rapidly and Reproducibly Alters the Human Gut Microbiome,” Nature 505 (January 23, 2014): 559–563, doi:10.1038/nature.12820.
  3. Andrew B. Shreiner, John Y. Kao, and Vincent B. Young, “The Gut Microbiome in Health and in Disease,” Current Opinion in Gastroenterology 31, no. 1 (January 2015): 69–75, doi:10.1097/MOG.0000000000000139.
  4. David E. Andrich et al., “Altered Lipid Metabolism Impairs Skeletal Muscle Force in Young Rats Submitted to a Short-Term High Fat Diet,” Frontiers in Physiology 9 (September 26, 2018): id. 1327, doi:10.3389/fphys.2018.01327; Alexandra Aliluev et al., “Diet-Induced Alteration of Intestinal Stem Cell Function Underlies Obesity and Prediabetes in Mice,” Nature Metabolism 3 (September 2021): 1202–1216, doi:10.1038/s42255-021-00458-9; Michael S. F. Wiedemann et al., “Adipose Tissue Inflammation Contributes to Short-Term High-Fat Diet-Induced Hepatic Insulin Resistance,” American Journal of Physiology, Endocrinology and Metabolism 305, no. 3 (August 2013): 388–395, doi:10.1152/ajpendo.00179.2013.
  5. Bisanz et al., “Meta-Analysis Reveals,” 559.
  6. Lindsay M. Edwards et al., “Short-Term Consumption of a High-Fat Diet Impairs Whole-Body Efficiency and Cognitive Function in Sedentary Men,” FASEB Journal 25, no. 3 (March 2011): 1088–1096, doi:10.1096/fj.10-171983.