The Metabolic Plant Feedback Hypothesis: How Plant Secondary Metabolites Nonspecifically Impact Human Health

Abstract

Humans can ingest gram amounts of plant secondary metabolites daily through diet. Many of these phytochemicals are bioactive beyond our current understanding because they act through weak negative biological feedback mechanisms, undetectable in vitro. Homeostatic-type assessments shed light on the evolutionary implications of the human diet from plants, giving rise to the metabolic plant feedback hypothesis. The hypothesis states that ancient diets rich in carbohydrates coincide with bulk dietary phytochemicals that act as nonspecific inhibitors of metabolic and inflammatory processes. Consequently, food-derived phytochemicals are likely to be equally effective as herbal medicines for these indications. In addition to the ubiquitous flavonoids, terpenoids, and fatty acids in the diet, the likely impact of chronic chlorophyll ingestion on human health is discussed, and data on its modulation of blood glucose levels are presented. A major deduction of this hypothesis is that starchy diets lacking plant secondary metabolites are associated with multimorbidity (lifestyle diseases) including obesity, type 2 diabetes, and cardiovascular disease. It is proposed that the intake of leafy vegetables, spices, and herbal remedies rich in phytochemicals matches the transition and genetic adaptation to early agriculture, playing a compensatory role in the mismatch of old genes and new diets.

Cannabimimetic phytochemicals in the diet – an evolutionary link to food selection and metabolic stress adaptation?

“…Nevertheless, chemical diversity in plants is shaped by environmental conditions and predation pressure, leading to vitamin‐like (i.e. essential), nonspecific (Gertsch, ) or even xenohormetic secondary metabolites (Lamming et al ., ; Howitz and Sinclair, ) in the Animalia food pyramid. Neurotransmitters, modulators and hormones naturally have very short half‐lives and are not generally orally bioavailable due to the metabolic enzymes present in most tissues, including the GI tract.…”

“…There is compelling evidence that numerous vegetables and spices exert beneficial effects in the context of obesity, the metabolic syndrome and diabetes (Leiherer et al ., ). There could even be a diet‐mediated metabolic plant feedback beyond nutrients and vitamins (Gertsch, ). Diet is important for the development of the immune system, stress axis and neurobiological fitness in infants, and the ECS appears to play a critical role in this process (Harrison and Baune, ; Moretti et al ., ).…”

“…Many other cell types seem to express low amounts of CB 2 receptors, although they may not be present functionally at the cell surface (Kleyer et al ., ). CB 2 receptors have been shown to protect tissues from fibrotic processes, possibly also by modulating macrophage polarization (Pacher and Mechoulam, ; Gertsch, ). Intriguingly, CB 2 receptors have more recently been shown to stimulate a number of positive metabolic processes leading to antidiabetic effects and cardiometabolic protection ( vide infra ).…”

Screening of Selected Sri Lankan Seasonal Fruit Extracts for Total Antioxidant Activity in vitro

“…Medical and nutritional research has for decades, emphasized the health benefits of consuming fruits and their role in the management/ prevention of chronic diseases/conditions such as cardiovascular disease, certain cancers, type II diabetes mellitus, obesity, chronic kidney disease, chronic lung disease, chronic obstructive pulmonary disease etc 3 . Further, the World Health Organization estimation data has revealed that, approximately 1.7 million (2.8%) deaths from diet related chronic diseases per annum are linked with low consumption of fruits and vegetables 2 .The importance of consumption of fruits and their involvement in the protection of cells from oxidative stress has become a debatable topic in this era 4 . In particular, phytochemicals with antioxidant potential are wellreported to play a role in reducing the consequences of oxidative stress in disease development and in aging process, thus contribute to overall health-protective effects 5 .…”

The Intricate Influence of the Placebo Effect on Medical Cannabis and Cannabinoids

“…For the great majority of medicinal plants, the underlying molecular mechanisms of action remain unknown, thus holding a promise for drug discovery [4]. From an evolutionary point of view, most plant secondary metabolites might be weak nonspecific modulators of mammalian proteins via our diet and execute chronic health benefits [5]. Like most medicines, botanical drugs can trigger placebo effects and thus represent ancient symbols of a meaning response (vide in-Med Cannabis Cannabinoids 2018;1:60-64 DOI: 10.1159/000489291 fra), a term coined by Moerman and Jonas [6].…”