Interactions are occurring in the course of liberation, absorption, distribution, metabolism,
and excretion of active ingredients, or at the target receptors. They are causing therapy
failures and undesirable events. Forty-seven of fifty-seven human hepatic isoenzymes are
specific and relevant in hormone and vitamin metabolism and biosynthesis. Aromatase
(syn. CYP19A1) is one of the specific CYP450 isoenzymes so far not elucidated in detail.
As aromatase-inhibiting phytochemicals are currently recommended for breast cancer
prevention and as add-on accompanying aromatase-inhibitor pharmacotherapy, it was
the aim of this literature review to assess whether a common interpretation on genetic
and -omics basis could be found. Articles retrieved showed that traditional antioxidation
diet is one of the most approved explanations of inhibition of aromatase by phytonutrients
of flavonoid derivatives. Flavonoids compete for the oxygen provided by the heme moiety
of aromatase in the course of aromatase-catalyzed conversion of steroid precursors to
estrogens. Flavonoids are therefore promoted for breast cancer prevention. A further
explanation of flavonoids’ mechanism of action proposed was related to enzymatic
histone deacetylation. By keeping DNA-structure wide through a high acetylation degree,
acetylated histones favor transcription and replication. This mechanism corresponds
to a procedure of switching genes on. Inhibiting acetylation and therefore switching
genes off might be an important regulation of repressing cancer genes. Aromatase
expression depends on the genotype and phenotype of a person. Aromatase itself
depends on the expression of the heme moiety encoded in the genotype. Biosynthesis
of porphyrins in turn depends on the substrates succinate and glycine, as well as
on a series of further enzymes, with ALA synthetase as the rate-limiting step. The
effect of the heme moiety as prosthetic group of aromatase further depends on the
absorption of iron as a function of pH and redox state. To assess the function of
aromatase precisely, multiple underlying biochemical pathways need to be evaluated.
As a conclusion, the genetic regulation of metabolism is a complex procedure affecting
multiple pathways. To understand a metabolic step, multiple underlying individually
performing reactions need to be considered if personalized (nutritional) medicine should
bring an advantage for a patient. Nutrition sciences need to consider the genome
of an individual to truly find answers to nutrition-derived non-communicable diseasesWith current GWAS (genome-wide association study) approaches, inherited errors of
metabolism are identified and ideally treated effectively. It is much more difficult to get
a precise genetic profile for non-communicable diseases stemming from multifactorial
causes. Polygenic risks evaluation is feasible but diagnostic tools are not yet available in
a desired extent. Neither flavonoid researchers nor providers of genetic testing kits are
going into the details needed for a truly personalized nutritional medicine. The next step
with profiling the exome and then the whole genome is on the threshold of becoming
routine diagnosis and of bringing the desired details.
Keywords: nutrients, nutrigenomics, aromatase, CYP19A1 isoenzyme, food-drug interactions, healthy aging,
personalized nutritional medicine, flavonoid
