Modified citrus pectin may act as a natural chelating agent, helping to remove excess heavy metals from the body. Using MCP for heavy metal detoxification is appealing due to the fact that it may have fewer side effects and be less invasive than other types of chelation therapy. In the EU, MCP holds potential for strengthening immune and overall health formulas when combined with ingredients approved by the European Food Safety Authority (EFSA) for immunity: beta-glucans, astaxanthin, Grifola frondosa (Maitake) and Lentinus edodes (Shiitake), vitamins B6, C and D, and methylsulfonylmethane (MSM). GAL3 expression is upregulated in fibrotic lesions in human subjects 63, and the severity of hepatic and lung fibrosis is reduced in GAL3-deficient mice 33, 142, 143, 144, 145. Thus, GAL3 has emerged as a promising therapeutic target for fibrotic diseases. Mechanistically, GAL3 induces a pro-fibrotic macrophage phenotype by interacting with the neutral amino acid transporter CD98 (ref. 123). Likewise, GAL3-secreting macrophages drive myofibroblast differentiation, which ultimately results in scar formation 146. Moreover, ECs and myofibroblasts upregulate GAL3 expression upon their activation 142, 147, 148; this facilitates EMT, apoptosis, myofibroblast proliferation and enhanced production of fibronectin and other proteins found in the extracellular matrix 149, 150, 151.

Other research studies show how MCP eliminates heavy metals, like mercury and lead, from the body. There are five studies of MCP in humans (where it is used alone or with green algae) showing its ability togreatly reduce the levelof heavy metals in the body. For example,one study (6) showed it encouraged the excretion of heavy metals like chromium, lead and arsenic from the body. Inflammatory degenerative diseases — from cardiovascular disease and cancer to neurodegenerative disease and many others — continue to surpass epidemic magnitudes worldwide, challenging researchers to better understand upstream drivers and identify key therapeutic targets. MCP may also help to improve the permeability of the gut wall (“leaky gut”). In one randomized clinical trial, 57 male infants with diarrhea were fed either pectin, a green banana, or a rice diet. Plant-derived polysaccharides have also been proposed as therapeutics for liver, kidney and lung fibrosis, mainly via mechanisms that involve inhibition of GAL3 (refs. 142, 146). Inhibition of GAL3 with belapectin ( 18, Fig. 4) and Davanat ( 19, Fig. 4) was first evaluated in a toxin-induced model of liver fibrosis 232. Intraperitoneal administration of these polysaccharides resulted in decreased collagen content, attenuated liver fibrosis, diminished cirrhosis and a reduced percentage of GAL3-expressing macrophages 232. These two inhibitors were also tested in a murine model of NASH 233. Intravenous administration of belapectin resulted in a substantial reduction in collagen deposition, hepatocellular damage, NASH activity and fibrosis — features that were associated with reduced markers of inflammation that included inducible nitric oxide synthase (iNOS) and CD36 + pro-inflammatory macrophages. By contrast, administration of Davanat had no effect 233. A phase I clinical trial of belapectin ( 18) in patients with NASH with advanced hepatic fibrosis revealed no toxicity and good tolerability 234 (NCT01899859, Table 1). Two phase II clinical trials evaluated the efficacy of this compound in liver fibrosis. In patients with NASH with advanced fibrosis (NCT02421094, Table 1), belapectin had no significant effects on levels of non-invasive biomarkers of liver inflammation or fibrosis over a 4-month period 234. In liver fibrosis and resultant portal hypertension in patients with NASH cirrhosis 235 (NCT02462967, Table 1), belapectin had no impact on fibrosis or nonalcoholic fatty liver disease activity score. However, in a patient subgroup it showed a significant effect on portal pressure and prevented the development of oesophageal varices, which is an early sign of serious complications in patients with cirrhosis. This led to the development of a phase IIb/III trial designed to evaluate its safety and efficacy specifically in patients with NASH-associated cirrhosis for the prevention of oesophageal varices (NCT04365868, Table 1). There were also no negative side effects observed in a clinical trial involving children with lead toxicity in China. For three months, the hospitalized children between the ages of 5 and 12 were given 15 g of MCP in three divided doses a day [ 4].Safe heavy metal chelation: Three clinical studies highlight MCP as a safe chelator of heavy metals. MCP is shown to bind to toxic metals in the circulation, reducing blood levels and increasing the urinary excretion of lead, mercury, arsenic, cadmium and others — without disrupting essential minerals. 19–21 G. Hossein, et al., “Synergistic Effects of PectaSol-C Modified Citrus Pectin an Inhibitor of Galectin-3 and Paclitaxel on Apoptosis of Human SKOV-3 Ovarian Cancer Cells,” Asian Pac. J. Cancer Prev. 14(12), 7561–7568 (2013).

Another significant study investigated the role of Gal-3 as a driver of oxidative stress in human cardiac fibroblasts, spontaneously hypertensive animal models and human aortic stenosis tissue. Results showed Gal-3 downregulates the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts, uncovering a new pathway whereby Gal-3 fuels cardiac damage. Importantly, MCP treatment restored cardiac Prx-4 and improved oxidative status. 3 As our understanding of the role of galectins in cancer and fibrosis has improved, various chemical and biological agents that target GAL1, GAL3 and GAL9 have been developed. These agents include small-molecule chemical inhibitors, natural polysaccharides and their synthetic derivatives, peptides and peptidomimetics, and biological agents such as small interfering RNA (siRNA), aptamers, truncated galectins and neutralizing mAbs. In the next section, we describe both the advances and the difficulties in the development and clinical evaluation of current galectin-targeted agents. Small-molecule carbohydrate inhibitors GCS-100 ( 17, Fig. 4), developed by La Jolla Pharmaceutical Company, was initially developed as a potential inhibitor of GAL3. GCS-100 has broad antitumour activity, including inducing apoptosis of multiple myeloma cells 212, 224, 225, 226. Moreover, GCS-100 alone or in combination with BCL-2 homology domain 3 (BH3) mimetics induced apoptosis in acute myeloid leukaemia cells 227. A phase II clinical trial (NCT00514696) evaluated intravenous administration of GCS-100 in patients with chronic lymphocytic leukaemia. The inhibitor showed excellent tolerability and led to partial remission in 25% of patients and >50% shrinkage of lymph node lesions in 16% of patients. Lactose (Lac) and LacNAc disaccharides, the natural galectin ligands in glycoconjugates, have been evaluated as galectin inhibitors 37, 184. Substitution of LacNAc at O3′ with aromatic moieties has been explored extensively as a means to generate new and favourable π–arene interactions with the conserved Arg144 residue; this effort has resulted in the development of several effective GAL3 ligands, including a LacNAc derivative 163, 185, 186 ( 6, Fig. 3d). Alternatively, synthetic lactulose amines evaluated as galectin modulators were found to induce tumour cell apoptosis and inhibit homotypic cell aggregation and EC morphogenesis 187. More recently, Kishor and colleagues 188 explored interactions of GAL1 and GAL3 with lactulose ( 7, Fig. 3e) by crystallography and proposed this disaccharide as another scaffold for the design of novel galectin inhibitors.Optimal therapy of biochemically relapsed prostate cancer (BRPC) after local treatment is elusive. An established modified citrus pectin (PectaSol ®, P-MCP), a dietary polysaccharide, is an established antagonist of galectin-3, a carbohydrate-binding protein involved in cancer pathogenesis. Based on PSA dynamics, we report on the safety and the primary outcome analysis of a prospective phase II study of P-MCP in non-metastatic BRPC based. Sixty patients were enrolled, and one patient withdrew after a month. Patients ( n = 59) were given P-MCP, 4.8 grams X 3/day, for six months. The primary endpoint was the rate without PSA progression and improved PSA doubling time (PSADT). Secondary endpoints were the rate without radiologic progression and toxicity. Patients that did not progress by PSA and radiologically at six months continued for an additional twelve months. After six months, 78% ( n = 46) responded to therapy, with a decreased/stable PSA in 58% ( n = 34), or improvement of PSADT in 75% ( n = 44), and with negative scans, and entered the second twelve months treatment phase. Median PSADT improved significantly ( p = 0.003). Disease progression during the first 6 months was noted in only 22% ( n = 13), with PSA progression in 17% ( n = 10), and PSA and radiologic progression in 5% (n = 3). No patients developed grade 3 or 4 toxicity. In the US, the researched form of MCP is patented for structure-function health claims related to cellular, cardiovascular and immune health, as well as inflammation, fibrosis and toxic metal body burden.

Of all 49 patients, 22.5% had stabilized cancer and 12.3% were stable for longer than six months. One patient with metastasized prostate cancer had 50% fewer prostate-specific antigen (PSA) in his system after 16 weeks on modified citrus pectin. PSA levels may indicate the likelihood of prostate cancer progression [ 8]. More than 50 published clinical and preclinical studies on this form of MCP demonstrate its critical, multifaceted benefits against heart disease, cancer proliferation/metastasis, organ fibrosis and other conditions characterised by elevated Gal-3. But there are some differences between these natural pectins and the MCP variety. Our intestines can’t absorb pectin directly from fruits. But the modified version has shorter carbohydrate chains and a lower molecular weight [ 1], allowing it to be absorbed into the bloodstream where it can then potentially exert benefits. Benefits of Modified Citrus Pectin Food supplements should not be used as a substitute for a varied diet. If you are taking prescribed medication, have any medical condition or are pregnant or breast-feeding please consult your healthcare practitioner before taking food supplements.

Pairs Well With

The role of galectins in suppressing antitumour immunity involves multiple pathways linked to innate and adaptive immune responses. For example, the induction of tolerogenic dendritic cells is driven by GAL1 (refs. 120, 121), and the recruitment and differentiation of immunosuppressive (M2-type) macrophages is triggered by GAL1 (ref. 31), GAL3 (refs. 122, 123) or GAL9 (ref. 124). Differentiation and expansion of CD4 + and CD8 + regulatory T cells (T reg cells) is induced by GAL1 (refs. 103, 125, 126) and GAL9 (ref. 127); whereas apoptosis of effector T helper 1 (T H1), T H17 and CD8 + T cells is mediated by GAL1 (refs. 128, 129, 130, 131, 132) and GAL9 (ref. 133); synthesis of anti-inflammatory cytokines such as IL-10 and IL-27 is elicited by GAL1 (refs. 126, 134); inhibition of natural killer (NK) cell-mediated cytotoxicity 135 and expansion of monocytic myeloid-derived suppressor cells (MDSCs) is induced by GAL3 (ref. 136); T cell exclusion is orchestrated by GAL1 (ref. 92), and the inhibition of chemokine gradients for T cell infiltration occurs in response to GAL3 (ref. 137). PectaSol® Metal Detox has been clinically studied to support safe heavy metal toxin and radioactive particle removal from the body, and is formulated to provide additional support to prevent toxin reabsorption and redistribution through the gut wall.*