Effects of Various Multi-Nutrient Supplements on the Production and Extracellular Deposition of Collagen I and IV by Human Aortic Smooth Muscle Cells

Vadim Ivanov, M.D., Ph.D., Svetlana Ivanova, M.D., Aleksandra Niedzwiecki, Ph.D. and Matthias Rath, M.D.
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Journal of Cellular Medicine and Natural Health (August 2018)


Chronic vitamin deficiency is an underlying cause of many modern human chronic diseases, including cardiovascular disease (CVD).1 A major pathological mechanism leading to the development of CVD is loss of vascular-wall integrity, a structural weakness that triggers the atherosclerotic process.2 The arterial wall is composed of the constituent cells and surrounding extracellular matrix (ECM).3

Smooth muscle cells (SMC), the major cellular component of the arterial wall, contract and relax, altering the luminal diameter, which enables blood vessels to maintain an appropriate blood pressure and to facilitate the redistribution of blood in the body. In addition, SMCs synthesize large amounts of extracellular matrix (ECM), the component responsible for providing the mechanical strength and integrity of the arterial wall, in order to contain the blood and to withstand pulsating pressure waves radiating from the beating heart.4

Collagen fibrils form the backbone of the extracellular matrix.5 The proper ECM assembly in the arterial wall is largely dependent on the quantity and quality of collagen molecules produced and deposited by SMC. It has been known for many years that vitamin C, ascorbic acid, is a key indispensable cofactor of specific enzymes regulating the limiting steps in collagen synthesis.6

Humans lost the ability to produce vitamin C internally, owing to the inactivating mutation of the gulonolactone oxidase gene (GULO), coding for a key enzyme in the pathway of ascorbic acid biosynthesis. Thus, acute vitamin C deficiency in human diet causes scurvy, which is caused by weakening of the arterial wall ECM structure and is manifested by blood leaking through the blood-vessel walls. Although, today, complete vitamin C dietary deprivation is rare, chronic vitamin C insufficiency is quite common in modern society, owing to globalization of agriculture, food processing and storage. Chronic vitamin C deficiency triggers atherosclerotic changes in the vascular wall, which over decades can lead to the development of CVD.1,7

Vitamin and mineral supplements are designed to fill the gap in quality of everyday food by providing these and other essential nutrients. However, the composition and quality of vitamin supplements vary widely from manufacturer to manufacturer. Most commercially available multi-nutrient formulas contain randomly selected ingredients in arbitrary doses. This is in contrast to the formulas developed according to synergistic effects of nutrients, an approach pioneered in the work of the Dr Rath Research Institute [www.drrathresearch.org]. Since there are no regulatory requirements demanding scientific proof of the efficacy of nutritional supplements marketed to consumers, many manufacturers promote their products using mere marketing slogans. In best cases, information about the formulas refers to the available published studies, with select individual components contained in the formulation. However, the overall effects of a combination of several nutrients can bring different outcomes from those when each one is used individually.

Therefore, the goal of this study was to determine the efficacy of various popular European and US consumer-market multivitamin formulations, on collagen production and ECM deposition by cultured smooth muscle cells isolated from human aortas.

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