Last week I talked about fad diets and Metabolic Syndrome (the syndrome of obesity, high blood pressure, low serum HDL’s, high serum triglycerides, and elevated fasting glucose). Metabolic Syndrome is caused by an imbalance between energy consumption and energy utilization by the body. Quite simply, too many calories are being consumed and too few calories are being used in metabolism. This simple equation, though, is just the start of the discussion of the syndrome because, quite possibly, it is not just the amounts of calories being consumed but the types of calories (and this is the foundation of many of the fad diets I talked about last week). It is also possible that modern foods because of the nature of their cultivation, growth, processing or preparation tip the metabolic balance of a person’s physiology to obesity and to the array of Metabolic Syndrome signs. It is also possible that our modern lifestyle has so modified (or destroyed) our natural, bacterial microbiome that these important mutualistic organisms no longer help us to control the flow of energy through our bodies.
There is, though, another way to look at our interactions with food and eating. Possibly, the constancy of food availability due to the efficiency of our agricultural systems has disrupted our natural metabolic cycles, or, possibly, our natural, day/night activity patterns have been so compromised by artificial lights and societal activity patterns, that the circadian rhythms of our body’s homeostasis have spun out of control.
Let’s think about how we have consumed food through most of our evolutionary existence. One very influential evolutionary model stresses periods of feast and famine. Hunter-gatherer humans eked out a meager, barely sustainable existence by gathering edible roots, plants and seeds from their surrounding environments. These times of low calorie acquisition were then punctuated by hunters from the human group bringing in large game items upon which the tribe would then feast. This model has led some to propose that human physiology, since it evolved under stresses of feast and famine, would work most optimally if extended period of fasting (one to several days) were intruded into a person’s weekly or monthly feeding cycles.
This hunter model has a distinctly male orientation (and, not surprisingly, it was written primarily by male ethnologists who were predominantly in contact with the males of the tribes they were studying). This model emphasizes the bravery, skill and potential sacrifice (limb and life!) of the male hunters to sustain the vigor and continued existence of their tribe. It is also, upon closer examination particularly of low latitude hunter/gatherer peoples, not at all accurate.
Present day hunter/gatherer societies (with the exception of those in high latitude (resource limited) environments) derive two-thirds of their caloric intake from plant food sources (K. Milton, The American Journal of Clinical Nutrition, December 2000). Often these tribes rely heavily upon a specific plant’s seed, nut, stalk or root that is abundantly and consistently available in their environments (like the iKung in the Kalahari and the mongongo nut, or the tribes in New Guinea and the wild sago palm, or the native American tribes in California and acorns from wild oak trees). These sustaining plants are easy to find in the tribe’s environment and not difficult or dangerous to gather and harvest. Even in habitats like the game-rich Serengeti of Tanzania, the hunter/gatherer people (the Hazda) primarily rely on wild plants for their food.
The idea, then, they humans evolved under this extended stress period of caloric deprivation is probably not accurate. There is, though, a more subtle way to think about fasting. Within a twenty-four hour period, humans were, under natural conditions, active during the daylight hours and inactive at night. Were the genes and proteins that regulate digestive metabolism influenced by this very distinct day/night pattern? If so, do they still exhibit this day/night tendency? Is it possible to use intermittent fasting (fasting for the length of the “night” interval of a twenty-four hour period) to optimize the activity of these genes and proteins? These types of fasts are referred to as “time-restricted feedings,” and they are the focus of some very interesting research (as summarized in an article by B. Grant in The Scientist, June 1, 2017).
The liver is the organ that controls almost all of intermediate metabolism for the body. The products of digestion (the sugars, amino acids, and, eventually, the lipids) all pass through the liver for processing, storage, or subsequent transport to the other cells of the body. The genes that regulate the activity of these vital liver cells turn on and off during each twenty-four time period. Experiments in mice showed that 90% of the liver cell genes stop their activity oscillations during periods of intermittent, twenty-four hour fasts or time restricted feedings of 8, 9, and 12 hours (during the twenty-four period). Stopping these oscillations increased insulin sensitivity (i.e. decreased insulin resistance), decreased blood glucose and protected the mice against diabetes, cardiovascular disease, high cholesterol, and fatty liver disease.
In the brain, neurons in times of caloric restriction make proteins that help to protect themselves from DNA damage or protein degradation. One of these proteins, “brain derived neurotropic factor” (BDNF), increases under these types of stresses and leads to greater number of mitochondria in the neurons of the hippocampus (the part of the brain involved in the consolidation of short-term memory into long-term memory). In fasting rats, the increased energy robustness of these vital memory neurons may explain their improved performance on learning and memory tests. Further, fasting, along with exercise reduces inflammation in the brain tissue by decreasing levels of inflammatory cytokines and stimulates the hippocampal neurons to grow nerve fibers and make new synapses! These impacts on the hippocampus may be the basis of memory improvement after fasting that is seen in Alzheimer’s disease animal models and animal post-ischemic stroke experiments.
The immune system is also affected by periodic fasting. In mice, the autoimmune T-lymphocytes of Multiple Sclerosis decrease both in number and activity after fasting. This reduces the destruction of myelin sheath around nerve fibers. Further, oligodendrocytes (the glial cell in the Central Nervous System that synthesizes myelin) are stimulated after fasting and re-myelination of many damaged nerve fibers occurs. In the mouse-model of Multiple Sclerosis, 20% of the mice went into non-symptomatic states and 50% went into less severe symptomatic states after fasting.
Cancer treatments (using mouse models of breast cancer and melanoma) that couple chemotherapy with fasting showed a synergistic effect leading to accelerated control and destruction of the cancerous cells. Researchers feel that the fasting preferentially stresses the rapidly replicating cancer cells while simultaneously stimulating stem cells to replace the cancerous cells with normal cells. There are suggestions, then, that not only the epidemic of Metabolic Syndrome but also the incidence of diabetes, Alzheimer’s disease, Multiple Sclerosis and cancer may be treatable with some sort of fasting co-therapy. Consideration of our evolutionary history takes us in such surprising directions!