Significant Dietary Changes during Human Evolution and the Development of Cancer: From Cells in Trouble to Cells Causing Trouble

Abstract

In all western societies, mortality rates from cancer are high and even increasing. In striking contrast, cancer rates are very rare and even non-existent in primitive cultures, like hunter-gatherer (HG) populations. HGs are free of disease as long as they adhere to their traditional low-insulinemic "Paleolithic" nutrition. With acculturation and transition to current high-carbohydrate/high-insulinemic "Western" diets (HCHIDs), cancer develops in high rates. This paper follows the question of how significant nutritional changes, brought about by the Agricultural revolution, may cause development of cancer. The evidence presented shows that the switch from a Paleolithic to a Western nutrition has brought about significant metabolic perturbations, like an abnormally increased activation of the insulinlike growth factor system, the sympathetic nervous system and the renin-angiotensin-system, an increased expression of HIF-1α and other more, all of which are deeply involved in cancer development through promotion of proliferation, angiogenesis, inflammation, macrophage infiltration, metastasis and inhibition of apoptosis.In addition, HCHIDs generate oxidative stress which may cause mitochondrial damage and genomic instability, and may interfere with normal stem cell development. Faulty redox signaling is suggested to play a significant role in cancer development: hydrogen peroxide, generated at low concentrations, represents an important chemical mediator in the regulation of various cellular signal transduction processes, including stem cell development. Oxidative stress may be sensed by cells as redox signaling. Faulty "redox signaling" is proposed to affect normal stem cell development by sustained activation of uncoupling protein 2, leading to inhibition of differentiation ("maturation arrest"), sustained uncontrolled proliferation, and glycolysis with high expression of hexokinase II, typical features of cancer. In summary, an abnormal diet-related activation of various metabolic systems, together with faulty redox signaling, is suggested to play a pivotal role in cancer development.

Diet-Induced Hyperinsulinemia as a Key Factor in the Etiology of Both Benign Prostatic Hyperplasia and Essential Hypertension?

“…In summary, BPH and hypertension share the same pathophysiological alterations, with hyperinsulinemia as the driving force. High-insulinemic diets may play a key role in the development of hyperinsulinemia and IR 104 and therefore in the etiology of EH and BPH, as the following sections show.…”

“…141 With the transition from LGLIDs to HGHIDs, insulin has gained a dominant position in human metabolism, resulting in a disruption of a finely tuned metabolic balance that has evolved over millions of years of evolution. As a result, hyperinsulinemia and IR may develop, accompanied by an abnormal activation of several metabolic systems, like the SNS and the RAAS 104,142 alterations that are deeply involved in the development of several diseases, including hypertension and BPH, as shown above.…”

“…The transition to a "Western-style" HGHID, whether by migration or acculturation, invariably leads to a dramatic increase in IR and hyperinsulinemia, 136,137 obesity and the MetS, 119,121,136,138 and cancer. 104 On the contrary, a return to a traditional, low-insulinemic diet is associated with marked improvement in IR and fasting insulin levels. 121,139,140 The notion that Stone Agers usually do not live long enough to develop degenerative diseases is not accurate.…”

“…High-glycemic/high-insulinogenic diets may play a key role in the development of hyperinsulinemia. 104,145,165 These diets elicit a high postprandial insulin response. Along with a "Western dietary pattern" of frequent snacking and frequent consumption of sucrose-containing soft drinks, insulin levels are elevated most of the day.…”

“…β-cells, genetically not adapted to this high insulin demand, may react with hypertrophy, functional dysregulation, and finally overresponsiveness and hyperinsulinemia. 104,167 Depending on the individual texture of the β-cells, hyperinsulinemia and IR may develop rapidly or increase gradually with increasing age.…”