Medicines and Vegetable Oils as Hidden Causes of Cardiovascular Disease and Diabetes

Abstract

Background: Positive associations have been observed between cardiovascular disease (CVD) and type 2 diabetes mellitus (DM), but their causal relationship has not been clarified. Nevertheless, guidelines from relevant medical societies recommend using cholesterol lowering medication (statin) for both types of patients. Medicines with several different action mechanisms have been developed, and the effectiveness of different lifestyle modifications has been studied extensively for the prevention of DM, which was successful in improving clinical marker status in relatively short-term treatments, but none have been shown to be effective in improving long-term outcomes (mortality from CVD and all causes). Summary: Statin-induced suppression of prenyl intermediates in the cholesterol biosynthetic pathway has been linked to stimulated atherosclerosis and heart failure. On the other hand, certain types of vegetable oil and hydrogenated oil shortened the survival of stroke-prone spontaneously hypertensive rats by decreasing platelet number, increasing hemorrhagic tendency and damaging kidney functions, which could not be accounted for by their fatty acid and phytosterol compositions. These vegetable oils and medicines such as statin and warfarin share, in part, a common mechanism to inhibit vitamin K₂-dependent processes, which was interpreted to lead to increased onset of CVD, DM, chronic kidney disease, bone fracture and even mental disorder. Impaired vitamin K₂-dependent processes by some types of vegetable oils and medicines, but not plasma high low density lipoprotein cholesterol, were proposed as the cause of CVD, DM and other lifestyle-related diseases. High n-6/n-3 fatty acid ratio of ingested foods, but not animal fats, was emphasized to be another risk factor for many of the diseases described above. Key Messages: To date, no randomized controlled trials (RCTs) have been performed to prove the above interpretation. However, the opposite types of RCT trials have been performed by increasing the intake of high-linoleic vegetable oils and reducing that of animal fats, which resulted in increased CVD and all-cause mortality. The amounts of these vegetable oils to exhibit adverse effects in animal studies are not huge (<6 energy %), which should not be overlooked nor disregarded.

A Critical Review of the Consensus Statement from the European Atherosclerosis Society Consensus Panel 2017

“…We have discussed this subject elsewhere [14, 42, 81] and expand on the broader aspects of statins’ adverse effects here.…”

“…VK2 regulates the activation (γ-carboxylation) of coagulation factors, osteocalcin (bone Gla protein), and matrix Gla protein. VK2 also acts on gene expression through the steroid and xenobiotic receptor (also known as the pregnane X receptor) to regulate the production of osteocalcin [14]. Understanding of the role of osteocalcin as a hormone secreted from bone marrow and targeting various organs has been increasing rapidly (Fig.…”

“…Some types of vegetable fats and oils, as well as warfarin, lead to various organ disorders by inhibiting VK2-dependent processes, as described in detail elsewhere [10, 14, 88]. Prenylation of Rab protein is necessary for the secretion of peptide hormones (Binnington et al [89]), and dolichols serve as carriers of carbohydrate moieties to form glycoproteins and glycolipids (Leconte et al [90]).…”

“…However, it should be noted that basic studies revealed the mechanisms by which statins lead to altered brain and testis functions [14, 95, 96]. In a mouse model devoid of synthesizing osteocalcin (Ocn), both c-Ocn (carboxylated) and uc-Ocn (undercarboxylated) were transferred to embryonic and offspring brains through the blood-brain barrier.…”

“…To assess the efficacy of treatments for the prevention of ASCVD, mortality rates (especially all-cause mortality) were considered the strongest objective end points, and composite end points, including hospitalization, revascularization, and stroke events were considered less objective. Statin RCTs published before 2004/2005 and any meta-analyses that included them were considered to be less reliable, for the reasons noted above [14]. In this review, we critically evaluate the EAS Consensus Statement 2017, emphasize the risks of statin medications, and propose new causes of ASCVD that do not involve elevated LDL-C levels.…”