The lay person is not familiar with the periodic table of elements, except for a select handful of elements that are so ubiquitous that we learned to recognise them in primary school, if not pre-school. Oxygen, hydrogen…. These always ring a bell because they form an integral part of our physiology and we consume them throughout the day. However, out of all the elements, there are also many others that participate in the myriad of chemical reactions that take place within our cells at any given moment. One of these elements, sulphur, incited a fascination in me when I learned how many special and therapeutic compounds depend on it for their structure and functions. In fact, I have already mentioned a handful of sulphur compounds in previous posts, such as the amino acids cysteine (also a component of the master antioxidant, glutathione) and methionine, S-adenosylmethionine. I will dedicate this post to a handful of special sulphur compounds, some of which are found in food and others which are produced as supplements.
| Compound | Therapeutic functions |
| Allicin | Allicin is naturally found in garlic, and is formed when garlic is chopped or crushed, triggering an enzymatic reaction. Allicin is also attributed to garlic’s strong odour and it’s use for therapeutic purposes is practically ancient, with a key example being Hippocrates, whom mentioned it’s benefits for treating pneumonia and for wound healing. Out of all the compounds present in garlic, allicin is almost exclusively responsible for garlic’s antimicrobial activity. In comparison to most commonly used antibiotics, allicin exhibits antimicrobial activity against a broader range of microorganisms, such as gram positive and gram negative bacteria and the methicillin-resistant Staphylococcus aureus (MRSA). Allicin’s antimicrobial properties can also be attributed to it’s oxidizing properties, as it is a reactive sulfur species and is able to oxidize thiols (sulfur groups) in cells, such as glutathione and cysteine residues in proteins, and a more oxidised glutathione pool leads to a higher cellular redox potential. Essentially, allicin can induce apoptosis (programmed cell death) in certain microbes via an oxidative route (Borlinghaus et al, 2014). Allicin exhibits immunomodulatory effects through several key mechanisms, such as inhibiting pro-inflammatory cytokines (IL-1b, IL-8, IP-10, MIG (monokine induced by gamma interferon)). Additionally, allicin attenuates iNOS (nitric oxide synthase) protein expression, NF-kb (nuclear factor kappa B) binding capacity, and TNF-a mediated T cell adhesion, implying that allicin has strong anti-inflammatory actions (Salehi et al, 2019). Given allicin’s therapeutic properties, it would be expected that allicin has shown promise in treating chronic illnesses. Treatment of cardiovascular disease with allicin, in particular, has been shown to be effective, as allicin can amend some of the mechanisms that drive CVD aetiology, whilst improving mechanisms that improve cardiovascular health overall. Allicin can; Induce vasorelaxation and prevent hyperlipidemia, which lowers blood pressure and cholesterol Vasorelaxation may come from the action of nitric oxide and inhibiting calcium movements Inhibition of hydroxymethylglutaryl-CoA reductase (HMG-CoA) and acyl-CoA cholesterol acyltransferase, enzymes involved in the production of cholesterol, results in allicin’s lipid-reducing effect Prevent cardiac hypertrophy (enlarging of the heart) Inhibit angiogenesis, the pathological process of vascular tissues where new blood vessel tissues develop from the originally existing ones Suppress platelet aggregation, a process where blood platelets adhere and aggregate on the surface of epithelial cells, which reduces lumen diameter and thus, increases resistance to blood flow and is a hallmark mechanism behind CVD (Chan et al, 2013) |
| Glucosamine sulfate | Glucosamine is a type of amino saccharide (sugar) called glycosaminoglycan (GAG), which is the preferred substrate for the biosynthesis of proteoglycans, which are molecules that contain protein and GAGs and are essential for maintaining cartilage integrity and function. Due to their negative charge, proteoglycans influence the storage of water enclosed in the cartilage and this is important for resiliency and elasticity of tissue as well as lubrication of the joint system (Jerosch, 2011). In supplementation, glucosamine is known to reduce proteoglycan loss, delay cartilage degeneration and joint-space narrowing and improve osteoarthritic pain in both animals and humans (Al-Saadi et al, 2019). Furthermore, a systematic review of studies using glucosamine sulfate as a therapeutic aid for people with knee osteoarthritis showed the same results, as daily doses of 1500 mg of glucosamine could positively modify cartilage structure, reduce pain and improve function (Veronese et al, 2020). Glucosamine in itself is not a sulfur compound, but it’s binding salt, sulfate is. Sulfate poses unique benefits that other salts do not and this is likely why sulfated glucosamine is favourable over other supplemental forms of glucosamine. It is clear that inflammation is a hallmark feature of degenerative joint diseases and NF-kB (a signalling molecule that enhances inflammatory processes) is known to be highly expressed rheumatoid and osteoarthritic synovitis and glucosamine sulfate has been shown to modify NF-kB activation, thus reducing expression of inflammatory genes, whilst promoting antioxidant enzymes, such as glutathione, superoxide dismutase, catalase, and glutathione peroxidases (Mendis et al, 2008). Glucosamine sulfate also inhibits pro-inflammatory cytokines, such as phospholipase A2, prostaglandin E2, nitric oxide, and cyclooxygenase-2 (Jerosch, 2011). |
| Methylsulfonylmethane (MSM) | Methylsulfonylmethane was primarily used as a commercial solvent, just like it’s parent compound, DMSO, which was found to have a host of therapeutic properties and the researchers that discovered this had postulated that other sulphur metabolites could possess the same benefits. MSM is a naturally-occurring compound within the earth’s sulphur cycle. Marine microorganisms metabolise sulfate into sulphur metabolites that are converted into dimethyl sulfide (DMS). The DMS in the ocean is aerosolised and oxidised to from DMSO or sulphur dioxide, which is then broken down into MSM or dimethyl sulfide. MSM’s benefits revolve around it’s ability to interfere with oxidative stress and inflammatory processes. MSM has been shown to inhibit the expression of inflammatory cytokines and modulate the transcription of genes associated with inflammation. For example, MSM can inhibit the NF-kB pathway, which up-regulates genes that encode cytokines, chemokines, and adhesion molecules, such as interleukin-1, interleukin-6, and tumor necrosis factor-a (TNF-a) (Butawan et al, 2017). MSM is frequently mentioned as a supportive compound for joints and this is partly because sulphur (which comprises 34% of MSM) is an important component of cartilage. In conditions where joints become painful and degrade, such as arthritis, where an imbalance between cartilage homeostasis and destruction leads to impaired synthesis of new cartilage cells, the consequential inflammation as a result of this process exacerbates joint destruction. In this case, MSM has been shown to promote osteoblast (bone cells) and chondrocyte (cell that creates structural components of cartilage) formation via up-regulating genes that promote these processes. In cases of joint paint, MSM was shown to significantly improve pain scores in comparison to placebo at 12 weeks. These improvements were seen in both wake-up (morning) pain and standing pain (Toguchi et al, 2023) In trials reviewing MSM as a treatment for obesity in mice, it was determined that MSM can protect against diet-induced obesity, insulin resistance, hepatic steatosis (fat accumulation in the live), inflammation, and disrupted bone microarchitecture. These findings also indicate the therapeutic potential of MSM in treating other chronic illnesses associated with obesity, such as metabolic syndrome and diabetes type 2, as MSM can markedly decrease triglycerides and blood glucose levels (Sousa-Lima et al, 2016). |
| Dimethyl sulfoxide (DMSO) | Dimethyl sulfoxide’s therapeutic benefits are broad and have been noted in treatment of a wide variety of illnesses, such as gastrointestinal, dermatological, urinary, rheumatic and renal diseases. As DMSO crosses the blood-brain barrier, it has also been used in the treatment of cerebral oedema. The basis behind DMSO’s benefits lie in it’s potent anti-inflammatory and antioxidant activity. DMSO has varied molecular effects that broadly influence biochemistry. For example, DMSO can accelerate the mobilisation of intracellular LDL cholesterol and prevent the rise in serum cholesterol and it’s accumulation in vascular and extravascular tissues. Additionally, DMSO has been shown to have marked effects that influence cell cycle, cell differentiation and cell death, by inducing apoptosis, arresting cell cycle, and induce differentiation in studies using malignant cells, indicating that DMSO could be a useful adjunct in cancer treatments (Santos et al, 2003). Further research conducted on human cancer cells confirms DMSO’s anti-cancerous effects. In solutions of higher DMSO concentration, ranging from 4%-10%, significant inhibition of myeloid leukemia and epithelial cancerous cells was observed whilst also inducing cell death and growth inhibition was attributed to DMSO’s effect in down-regulating proteins that regulate cell cycle progression, such as CDK2 and cyclin A (Tang et al, 2020). Alluding to DMSO’s anti-inflammatory effects, even at a very low concentration of 0.5%, DMSO could inhibit the secretion of pro-inflammatory cytokines from E. Coli and HSV-1 (herpes simplex virus), such as G-CSF (granulocyte colony-stimulating factor), IFNy (interferon gamma), IFNa (interferon alpha) and PGE2 (prostaglandin E2). In research conducted on monocytes (human cells that produce cytokines/chemokines), DMSO was shows to inhibit different cell-signalling pathways (ERK1/2, p38, PI3K/Akt and JNK) that promote inflammation. In this instance, DMSO can reduce the recruitment of immune cells, such as neutrophils, into sites where inflammation is present and these effects may explain why DMSO has been succesful in mitigating symptoms of autoimmune arthritis (Elisa et al, 2016). Moreover, DMSO’s aid for autoimmune conditions could be partly attributed to it’s ability to abolish antigen-specific responses from T-lymphocytes, such as CD4+ and CD8+ (lymphocytes that drive inflammation), whilst also preventing the proliferation of T-lymphocytes into those effector cells (Costa et al, 2017). |
| N-acetyl cysteine | N-acetylcysteine is the acetylated precursor of the sulfur-containing amino acid cysteine and has been used to treat a broad range of conditions, such as respiratory tract infections (NAC is a mucolytic agent), paracetamol toxicity, angina, chemotherapy-induced toxicity, mental health disorders, amongst others. The most prevalent reason for NAC’s multi-functional use lies in it’s ability to promote the synthesis of glutathione, a major antioxidant and the ubiquitous source of thiols (sulfur compounds) in the body. Thiols are involved in detoxification, cell signalling, regulation of immune responses, production of inflammatory mediators, neurotransmitter signalling and cell proliferation. As it pertains to detoxification and mucolytic actions, NAC can reduce toxic compounds into benign metabolites and/or neutralise the free radicals formed by those compounds and also reduce disulfide bonds in proteins (altering their structure), such as mucous-linked proteins (Samuni et al, 2013). Alluding to NAC’s anti-inflammatory effects, intravenous use of NAC improved oxygen metrics and dyspnea in hospitalised patients with COVID-19. The onset of immune mediators and chemokines in response to the infection can induce drastic oxidative stress via free radicals which cannot be mitigated by our own defence systems. Excessive free radicals can further amplify the immune response, leading cell damage and dysfunction. As a precursor to glutathione, NAC likely reverses the inflammatory response that leads to potentially fatal complications in COVID-19 cases, as glutathione deficiency is thought to be the likely culprit behind the cause of those complications. Reductions in white blood cells, LDH (lactase dehydrogenase), Il-6 (interleukin-6), CRP (C-reactive protein), and D-dimer were readily observed as well, confirming NAC’s antioxidant and immuno-modulatory effects (Gamarra-Morales et al, 2023). As an adjunct to allopathic treatment for polycystic ovary syndrome (which commonly co-exists with metabolic syndrome), NAC improved ovulation and pregnancy rates and also improved insulin sensitivity, likely because of NAC’s antioxidant effects. Those effects may also explain why NAC can aid in preventing miscarriage and preterm birth, by mitigating infection and inflammation, which could incite apoptosis of placental tissues, and restore maternal and foetal oxidative balance. Essentially, NAC could be a useful treatment aid in any condition involving inflammation, as seen in cases of bronchitis and colitis (Mokhtari et al, 2016). NAC has shown promise in the treatment of mental health disorders via several pathways. Firstly, as a precursor to glutathione, NAC provides valuable reserves for glutathione (GSH) synthesis in the brain, as glial cells contain high levels of glutathione in comparison to neuronal cells and astrocytes release GSH into extracellular space where it can be broken down into glycine, cysteine and glutamate for neuronal GSH synthesis. Secondly, NAC’s anti-inflammatory actions could explain part of it’s benefit in treating psychiatric conditions, as alterations in cytokines, such as IL-6, IL-1b, and TNF-a, have been noted in patients with depression. And thirdly, NAC has marked effects on neurotransmitters, as cysteine assists in the exchange of glutamate within neurons and is exchanged for glutamate by astrocytes, which appears to stimulate inhibitory glutamate receptors and thereby reduce synaptic release of glutamate. NAC can also stimulate dopamine release and protect against reductions in dopamine transporter levels (Dean et al, 2011). |
| Taurine | Taurine is a non-essential amino acid that was first extracted from ox bile, hence the name “Taurus”. The sulphur present in taurine is in sulphonate form and can be oxidised into sulfate. The heart, liver, and brain are the only organs that can produce taurine in limited quantities but dietary sources, particularly meat, are rich in taurine. Biosynthesis of taurine requires methionine, which gets converted to cysteine, which can be converted to taurine but humans lack sufficient quantities of the enzyme (cysteine sulfinate decarboxylase) required for this step (Srivastava et al, 2022). Due to taurine’s unique chemical properties, it is found mainly within intracellular fluid of tissues, where it influences many physiological processes, For example, it acts as an osmolyte, regulating cell volume and maintaining integrity. In the liver, it conjugates bile acids, forming the bile salts that aid fat digestion ands fat-soluble vitamin absorption. Additionally, taurine is plays a role in calcium signalling, modulating ion channels, and neurotransmission, affecting synaptic transmission and neural excitability. Given that the brain has a high concentration of taurine, it is no surprise that it has been shown to influence neurotransmitter release and receptor function, affecting mood and cognitive processes, such as memory, behaviour, mood, and learning. There is ample research that confirm taurine’s cardiovascular benefits through several mechanisms. Given that taurine modulates ion channels, such as calcium and potassium, which are intrinsic to to the heart’s electrical activity and vascular tone, taurine affects the heart’s contractility, stroke volume, output and relaxation. By promoting nitric oxide, taurine improves endothelial function, which in turn contributres to better vascular function, reduced inflammation, and improve blood flow. This on top of taurine’s ion channel modulating action, likely account for it’s antihypertensive effects. Both animal and human studies show that taurine induces a modest reduction in blood pressure (Santulli et al, 2023). Additionally, taurine has shown to have anti-inflammatory effects, which add to it’s cardiovascular benefits. Metabolites of taurine, taurine-bromamine (TauBr) and taurine-chloramine (TauCl), can modulate inflammatory cell signalling pathways, such as toll-like receptor, Myeloid differentiation primary response 88 (MyD88), and NF-Kb (nuclear factor-kappa b). TauBr is formed when taurine reacts with the reactive oxygen species (ROS), hypobromous acid, and exerts anti-inflammatory effects by down-regulating tumour necrosis alpha-induced inflammation and pro-inflammatory interleukins. TauCl is formed when taurine reacts with the ROS, hypochlorous acid, and can inhibit mediators of toll like receptor 2, 4, and 9 inflammation, and modulate NF-Kb signal transduction. Inflammatory contributions by toll-like receptors have been implicated in the pathogenesis of atherosclerosis and cardiovascular disease (Qaradakhi et al, 2020). Expanding on taurine’s neurological benefits, extracellular taurine can bind to GABAa, GABAb and glycine receptors, augmenting it’s inhibitory effect. Excitotoxicity is mitigated by taurine through inhibiting protein kinase C, which prevents the activation of voltage-gated calcium channels and therefore decreasing calcium entry through these channels. This explains why taurine can mitigate the effects of glutamate-induced exitotoxicity because once glutamate binds to NMDA receptors, significant increases in intracellular loads of calcium and occur and taurine can mitigate this process (Ramirez-Guerrero et al, 2022). |
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