Abstract
One line summaryMetabolic syndrome and obesity-related co-morbidities are largely explained by co-adaptations to the energy use of the large human brain in the cortico-limbic-striatal and NRF2 systems.The medical, research and general community is unable to effect significantly decreased rates of central obesity and related type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer. All conditions seem to be linked by the concept of the metabolic syndrome (MetS), but the underlying causes are not known. MetS markers may have been mistaken for causes, thus many treatments are destined to be suboptimal.The current paper aims to critique current paradigms, give explanations for their persistence, and to return to first principles in an attempt to determine and clarify likely causes of MetS and obesity related comorbidities. A wide literature has been mined, study concepts analysed and the basics of human evolution and new biochemistry reviewed. A plausible, multifaceted composite unifying theory is formulated.The basis of the theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A ‘dual system’ is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals, becoming highly energy efficient in humans.The still-evolving, complex human cortico-limbic-striatal system generates strong behavioural drives for energy dense food procurement, including motivating agricultural technologies and social system development. Addiction to such foods, leading to neglect of nutritious but less appetizing ‘common or garden’ food, appears to have occurred. Insufficient consumption of food micronutrients prevents optimal human NRF2 function. Inefficient oxidation of excess energy forces central and non-adipose cells to store excess toxic lipid. Oxidative stress and metabolic inflammation, or metaflammation, allow susceptibility to infectious, degenerative atherosclerotic cardiovascular, autoimmune, neurodegenerative and dysplastic diseases.Other relevant human-specific co-adaptations are examined, and encompass the unusual ability to store fat, certain vitamin pathways, the generalised but flexible intestine and microbiota, and slow development and longevity.This theory has significant past and future corollaries, which are explored in a separate article by McGill, A-T, in Archives of Public Health, 72: 31.
Highlights
The major health problems that beset almost all populations in the 21st Century are degenerative disorders such as type II diabetes mellitus (TIIDM), atherosclerotic cardiovascular disease (CVD) and cancer
Unusual characteristic in humans such as slow development, growth and healthy longevity or the ability to gain very large amounts of fat in adipose tissue may be related to brain energy use
The composite unifying theory includes the ‘dual system’ theory and other human specific co-adaptations, as an explanation for malnubesity, a condition of excess fat accumulation which has a concomitant insufficiency of vitamins, minerals, plant and other micronutrients
Summary
The major health problems that beset almost all populations in the 21st Century are degenerative disorders such as type II diabetes mellitus (TIIDM), atherosclerotic cardiovascular disease (CVD) and cancer. The extended human lifespan is associated with delayed puberty, and the unusual occurrence of menopause and healthy life for many years after breeding, in females, ceases [63] This slow development and long life is likely to be largely dependent on the hyper-efficient cell protection mechanisms of the NRF2 systems exposed to a high micronutrient diet. These mechanisms comprise augmented antioxidation and repair afforded to long lived cells, as well as replication stability provided by antitoxicant action, especially in glandular epithelium and leukocytes. The NRF2 system’s power to maintain an extremely high level of antioxidant cell protection and detoxify persistent man-made chemicals depends on relative and absolute food micronutrient sufficiency
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