A Theoretical Framework For Evolutionary Medicine

Huaorani hunter in Ecuador

If you’re scientifically inclined, you’ll enjoy perusing the following article. Otherwise, quit now before it’s too late.

“Lifestyle and nutritional imbalances associated with Western diseases: causes and consequences of chronic systemic low-grade inflammation in an evolutionary context,” by Begoña Ruiz-Núñez, Leo Pruimboom, D.A. Janneke Dijck-Brouwer, and Frits A.J. Muskiet. It’s in the Journal of Nutritional Biochemistry, vol. 24, issue 7, pp. 1183-1201. http://dx.doi.org/10.1016/j.jnutbio.2013.02.009,

Here’s the 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.

I encourage you to read the whole article if you’re interested in such things. I’ll only mention certain concepts in this post if I want to learn or remember them for my own purposes.

The authors stress our large brains’ constant need for energy from glucose. This is how they explain our propensity to develop insulin resistance:

A glucose deficit leads to competition between organs for the available glucose. As previously mentioned, this occurs during fasting [and starvation], but also during pregnancy and infection/inflammation. Fasting is characterized by a generalized shortage of glucose (and other macronutrients), but in case of pregnancy and inflammation we deal with active compartments competing with the brain for the available glucose, i.e., the growing child and the activated immune system, respectively. During competition between organs for glucose, we fulfill the high glucose needs of the brain by a reallocation of the energy-rich nutrients, and to that end, we need to become insulin resistant.

During starvation and times of infection or inflammation, we divert glucose to our brains or immune systems via insulin resistance in certain tissues. These tissues can then use less glucose and more fat for energy. “…the adipose tissue compartment will be encouraged to distribute free fatty acids, while the liver will be encouraged to produce glucose via gluconeogenesis and to distribute triglycerides via very low-density lipoprotein (VLDL).”

This reallocation of energy—the aim of the process above—and the compensatory hyperinsulinemia “are meant for short-term survival, and their persistence as a chronic state are at the basis of the ultimate changes that we recognize as the symptoms of the metabolic syndrome, including the changes in glucose and lipid homeostasis and and the increasing blood pressure. For example, the concomitant hypertension has been explained by a disbalance between the effects of insulin on renal sodium reabsorption and NO-mediated vasodilatation, in which the latter effect, but not the first, becomes compromised by insulin resistance, causing salt sensitivity and hypertension.”

I warned you to get out before it was too late!

Looks like a great place to hike

I don’t ever recall reading how much energy our immune system uses. The authors write:

During infection/inflammation we deal with the metabolic needs of an activated immune system for acute survival. The inactive immune system consumes about 23% of our basal metabolism, of which as much as 69% derives from glucose (47%) and the glycogenic amino acid glutamine (22%). Upon activation, the energy requirement of our immune system may increase with about 9–30% of our basal metabolic rate. In multiple fractures, sepsis and extensive burns, we deal with increases up to 15–30, 50, and 100% of our basal metabolism, respectively.

The activated immune system, they say, functions mainly on glucose.

Summarizing thus far, we humans are extremely sensitive to glucose deficits, because our large brain functions mainly on glucose. During starvation, pregnancy and infection/inflammation, we become insulin resistant, along with many other adaptations. The goal is the reallocation of energy-rich substrates to spare glucose for the brain, the rapidly growing infant during the third trimester of pregnancy, and our activated immune system that also functions mainly on glucose. Under these conditions, the insulin resistant tissues are supplied with fatty acids. Other goals of the changes in the serum lipoprotein composition are their role in the modulation of the immune response by the clearance of LPS [lipopolysaccharides] during infection/inflammation and the redirection of cholesterol to tissues for local damage repair. The metabolic adaptations caused by inflammation illustrate the intimate relationship between our immune system and metabolism. This relation is designed for the short term. In a chronic state it eventually causes the metabolic syndrome and its sequelae. We are ourselves the cause of the chronicity. Our current Western lifestyle contains many false inflammatory triggers and is also characterized by a lack of inflammation suppressing factors.

The authors list many familiar components of the Western lifestyle that can cause chronic systemic low-grade inflammation, “which in turn leads to chronically compromised insulin sensitivity, compensatory hyperinsulinemia and, eventually, the diseases related to the metabolic syndrome”:

• the consumption of saturated fatty acids and industrially produced trans fatty acids
• a high ω6/ω3 fatty acid ratio
• a low intake of long-chain polyunsaturated fatty acids (LCP) of the ω3 series (LCPω3) from fish (EPA and DHA are most important)
• a low status of vitamin D and vitamin K and magnesium
• the “endotoxemia” of a high-fat low-fiber diet
• the consumption of carbohydrates with a high glycemic index and a diet with a high glycemic load
• a disbalance between the many micronutrients that make up our antioxidant/pro-oxidant network
• a low intake of fruit and vegetables
• an abnormal composition of the bacterial flora in the mouth, gut, and gingivae
• chronic stress
• smoking, second-hand smoke, and environmental pollution
• insufficient physical activity
• insufficient sleep
• excessive alcohol consumption
• low fiber intake
• meat from domesticated animals
• obesity

“Homo sapiens emerged about 160,000 years ago in East-Africa.”

In contrast to some (e.g., John Hawks?) who believe we are rapidly evolving, these authors think that our genome, “with an average effective mutation rate of 0.5% per million years,” still overwhelmingly reflects the Paleolithic era.

They support their contentions with 334 references.

Steve Parker, M.D.