Magnesium in joint health and osteoarthritis

Abstract

Osteoarthritis (OA) is a prevalent debilitating age-related skeletal disease. The hallmark of OA is the degradation of articular cartilage that cushions the joint during movement. It is characterized by chronic pain and disability. Magnesium, a critical trace element in the human body, plays a pivotal role in metabolism homeostasis and the energy balance. Humans obtain magnesium mainly from the diet. However, inadequate magnesium intake is not uncommon. Moreover, the magnesium status deteriorates with ageing. There has been a growing body of clinical studies pointing to an intimate relationship between dietary magnesium and OA although the conclusion remains controversial. As reported, the magnesium ion concentration is essential to determine cell fate. Firstly, the low-concentration magnesium ions induced human fibroblasts senescence. Magnesium supplementation was also able to mitigate chondrocyte apoptosis, and to facilitate chondrocyte proliferation and differentiation. In this literature review, we will outline the existing evidence in animals and humans. We will also discuss the controversies on plasma or intracellular level of magnesium as the indicator of magnesium status. In addition, we put forward the interplay between dietary magnesium intake and intestinal microbiome to modulate the inflammatory milieu in the conjecture of OA pathogenesis. This leads to an emerging hypothesis that the synergistic effect of magnesium and probiotics may open a new avenue for the prevention and treatment of OA.

Introduction

Osteoarthritis (OA) is a serious disease characterized by articular cartilage degradation and damages to the other joint tissues [1]. OA is one of the most rising disability-associated conditions, leading to poor quality of life in older adults [2]. Dietary nutrition can be used as an important non-pharmacological treatment for OA. A diet supplemented with vitamin D has a positive effect on the thickness of the joint cartilage and joint lubrication [3]. Olive oil reduces the release of pro-inflammatory cytokines and increases lubricin synthesis, suggesting a positive protective effect on the joints [4,5]. Vitamin E supplementation can significantly increase the level of circulating antioxidant enzymes and relieve the pain of knee OA [6]. Fat-soluble vitamin K can affect the mineralization of bones and cartilage, which is associated with OA [7]. Obesity induced by a high-fat and high-sugar diet can cause inflammation and promote the development of OA. Supplementing prebiotic fiber can prevent the increase of serum endotoxin and microbial dysbiosis, so that it can improve knee joint damage [8,9]. Increasing intake of dietary fiber can reduce the risk of OA as well [10].

Magnesium (Mg) is an important trace element. Since the human body cannot produce this mineral by itself, humans need to obtain Mg from their diet. Mg is predominantly obtained from the diet by consuming green leafy vegetables, unprocessed beans and grains. As the modern diet has drifted away from these food sources in favor of fine dining or nutrient-poor foods, inadequate Mg intake is common in developed western countries such as the United States and France [11,12]. The suboptimal Mg level further deteriorates with age [13]. An estimated 10% of older adults have a low plasma Mg level and 20% of them have a low concentration of erythrocyte Mg [14]. There are a few possible reasons for Mg deficiency in the elderly. First, the intestinal absorption of Mg decreases with age [15]. Second, Mg deficiency is often observed in patients with type 2 diabetes mellitus (T2DM) or those taking diuretics, the anti-hypertension medication [16]. Two conditions often occurring in the elderly. Finally, the Mg deficit is further intensified by an increased intake of calcium which is advised for osteoporosis prevention [17]. Low Mg, together with excessive calcium, predisposes an individual to cardiovascular diseases. Not surprisingly, there is a growing body of evidence to indicate a link between a Mg deficiency and a plethora of age-related diseases, including OA [18,19], osteoporosis [20], metabolic syndrome (MetS) [21,22], stroke, cognitive impairment [23] as well as hypertension and T2DM [16].

In this literature review, we aim to outline the existing evidence on the clinical and biological links between low dietary magnesium intake and OA and discuss potential interventions to address this challenge.