Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person

Abstract

Homocysteine (Hcy) metabolism is crucial for regulating methionine availability, protein homeostasis, and DNA-methylation presenting, therefore, key pathways in post-genomic and epigenetic regulation mechanisms. Consequently, impaired Hcy metabolism leading to elevated concentrations of Hcy in the blood plasma (hyperhomocysteinemia) is linked to the overproduction of free radicals, induced oxidative stress, mitochondrial impairments, systemic inflammation and increased risks of eye disorders, coronary artery diseases, atherosclerosis, myocardial infarction, ischemic stroke, thrombotic events, cancer development and progression, osteoporosis, neurodegenerative disorders, pregnancy complications, delayed healing processes, and poor COVID-19 outcomes, among others. This review focuses on the homocysteine metabolism impairments relevant for various pathological conditions. Innovative strategies in the framework of 3P medicine consider Hcy metabolic pathways as the specific target for in vitro diagnostics, predictive medical approaches, cost-effective preventive measures, and optimized treatments tailored to the individualized patient profiles in primary, secondary, and tertiary care.

Rapid triage for ischemic stroke: a machine learning-driven approach in the context of predictive, preventive and personalised medicine

“…Our current finding is consistent with prior research [50][51][52][53][54][55][56][57]. First, both human and animal studies revealed that ageing-related changes are associated with IS in terms of susceptibility, response to treatment, and prognosis [50]; relevant mechanisms may involve the accumulation of mitochondrial DNA, resulting in mitochondrial dysfunction which is associated with ageing-related neurological disorders, such as the pathological oxidative stress by ischemia-reperfusion damage [51,52]. Second, a clinical trial and a review have revealed the potential mechanisms regarding the neutrophil count on IS risk, suggesting the interactions with the endothelium and platelets and overactivity of neutrophil extracellular traps may play a key role [53,54].…”

“…Our current finding is consistent with prior research [50][51][52][53][54][55][56][57]. First, both human and animal studies revealed that ageing-related changes are associated with IS in terms of susceptibility, response to treatment, and prognosis [50]; relevant mechanisms may involve the accumulation of mitochondrial DNA, resulting in mitochondrial dysfunction which is associated with ageing-related neurological disorders, such as the pathological oxidative stress by ischemia-reperfusion damage [51,52].…”

Anti-breast cancer effects of phytochemicals: primary, secondary, and tertiary care

“…To this end, the majority of breast cancer cases are preventable that makes primary care to the key point in the paradigm change from the currently applied reactive disease management to the cost-effective 3PM approach [ 6 , 7 ]. Health risk assessment followed by targeted damage-mitigating measures and protection tailored to the individualized patient profile are instrumental to reverse health damage at the level of sub-optimal health [ 120 , 121 ]. As demonstrated above, an application of phytochemicals in the framework of primary care might be a particularly cost-effective approach exemplified by the evidence-based protection against the non-physiologic inflammation [ 35 ] and mitochondrial dysfunction [ 122 ] as well as against the Warburg malignant transformation [ 38 ].…”

Systemic Effects Reflected in Specific Biomarker Patterns Are Instrumental for the Paradigm Change in Prostate Cancer Management: A Strategic Paper

“…Non-physiologic homocysteine (Hcy) levels easily detectable in blood plasma leading, for example, to hyperhomocysteinemia (HHcy) are associated with several metabolic disorders, aberrant gene methylation and damage to DNA-altogether synergistically increasing risks of carcinogenesis in affected individuals as recently reviewed [20]. Specific polymorphisms in genes involved in the Hcy metabolism axes as well as diets deficient in folate, vitamin B6 or cobalamin correlate with HHcy and cascading pathologies.…”

“…Specific polymorphisms in genes involved in the Hcy metabolism axes as well as diets deficient in folate, vitamin B6 or cobalamin correlate with HHcy and cascading pathologies. Further, administration of drugs such as laxatives and immunosuppressive drugs, may lead to HHcy development and subsequent folate reduction associated with a number of associated disorders in affected individuals [20]. To this end, involved in the Hcy-axes specifically, imbalanced metabolism of vitamin B12 and folate has been associated with increased prostate cancer risk [21].…”