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The Protection and Toxic Reactions of Dietary Supplements: Focusing on Molecular Mechanisms and Treatment

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Bioorganic Chemistry and Medicinal Chemistry".

Deadline for manuscript submissions: 28 February 2025 | Viewed by 14475

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In Vitro Drug Safety and Biotechnology, Département of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M2R 1W6, Canada
Interests: inflammation and repair in liver disease; clinical, translational and molecular events in liver disease; gastroenterology; autoimmune hepatitis; alcoholic and non-alcoholic steato hepatitis; metabolic diseases; drug-induced organ injury; drug-induced liver injury; personalized therapies in the diseases of the liver; personalized immuno-oncology in hepatocellular carcinoma
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Special Issue Information

Dear Colleagues,

Dietary supplements include vitamins, minerals, amino acids, whey protein, creatine, and more. Dietary supplements and herbal medicines are very popular in many countries now. Although most people believe that dietary supplements can help us become more healthy, serious toxicities do occur due to the consumption of too many supplements. Some supplements can also cause problems if taken with certain medicines. For example, vitamins C and E may reduce the effectiveness of some chemotherapy drugs.

Complementary medicine is frequently integrated with conventional medicine. Prescription medicines are thoroughly tested before receiving regulatory approval, but despite this, real-world experience reveals undetectable adverse events in clinical trials. Complementary and alternative medicine are considered non-toxic by consumers. However, many of them might produce adverse reactions or interact with prescription medicine.

This Special Issue aims to report all the adverse effects of dietary supplements. We welcome the discussion of adverse events for commonly used supplements such as vitamins, minerals, plant extracts, and so on. We will also look into the protective or harmful effects of complementary and alternative use.

Importantly, the exact active ingredients of the natural origin extracts must be reported in submitted research manuscripts.

Prof. Dr. Neuman Manuela
Guest Editor

Manuscript Submission Information

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Keywords

  • dietary supplements
  • toxic reactions
  • protection mechanisms
  • bioactives
  • vitamins
  • minerals
  • amino acids

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Published Papers (8 papers)

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Research

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15 pages, 278 KiB  
Article
Dietary Oleic Acid and SCD16 and ELOVL6 Estimated Activities Can Modify Erythrocyte Membrane n-3 and n-6 HUFA Partition: A Pilot Study
by Paulo Bispo, Pedro O. Rodrigues and Narcisa M. Bandarra
Curr. Issues Mol. Biol. 2025, 47(2), 81; https://doi.org/10.3390/cimb47020081 - 27 Jan 2025
Viewed by 536
Abstract
In this work, we studied the relationships between the most representative fatty acids (FAs) and their ratios in red blood cell (RBC) membranes and dietary fatty acids alongside several cardiometabolic risk factors. Twenty-six individuals were enrolled with a mean age of 50.4 ± [...] Read more.
In this work, we studied the relationships between the most representative fatty acids (FAs) and their ratios in red blood cell (RBC) membranes and dietary fatty acids alongside several cardiometabolic risk factors. Twenty-six individuals were enrolled with a mean age of 50.4 ± 12.7 years (16 males and 10 females). By bivariate analysis, dietary oleic acid (OA) correlated negatively with C20:4n-6 (AA) (p = 0.031) in RBCs. With multivariate regression analysis, dietary OA (p < 0.001) is an independent predictor and negatively associated with AA levels in RBCs, while the elongation of very-long-chain fatty acids 6 (ELOVL6) and stearoyl-CoA desaturase 16 (SCD16) activities (p < 0.05) was positively associated with AA levels in RBCs. The multivariate regression models also showed that dietary OA was an independent predictor and positively associated with C22:5n-3 (DPA) in RBCs. Furthermore, BMI positively correlated with SCD16, and both SCD16 and SCD18 were positively associated with triacylglycerols levels. In addition, SCD16 positively and significantly correlated with LDL-c and the LDL-c/HDL-c ratio and negatively correlated with the ApoA1/ApoB ratio, and SCD16 and ELOVL6 were significantly associated with HDL molecular subfractions. Therefore, our data underline that OA, SCD16 and ELOVL6 can interfere with n-3 and n-6 partition in biomembranes such as RBCs, suggesting an important molecular (patho)physiological regulatory mechanism role in controlling bioactive molecules’ availability such as those involved in the immune-inflammatory response. Full article
15 pages, 2049 KiB  
Article
Feasibility Trial Exploring Immune-Related Biomarkers Pertaining to Rapid Immune Surveillance and Cytokine Changes after Consuming a Nutraceutical Supplement Containing Colostrum- and Egg-Based Low-Molecular-Weight Peptides
by Liu Yu, Ifeanyi Iloba, Dina Cruickshank and Gitte S. Jensen
Curr. Issues Mol. Biol. 2024, 46(7), 6710-6724; https://doi.org/10.3390/cimb46070400 - 30 Jun 2024
Viewed by 1985
Abstract
Immune protection associated with consuming colostrum-based peptides is effective against bacterial and viral insults. The goal for this study was to document acute changes to immune surveillance and cytokine levels after consuming a single dose of a nutraceutical blend in the absence of [...] Read more.
Immune protection associated with consuming colostrum-based peptides is effective against bacterial and viral insults. The goal for this study was to document acute changes to immune surveillance and cytokine levels after consuming a single dose of a nutraceutical blend in the absence of an immune challenge. A double-blind, randomized, placebo-controlled, cross-over pilot study involved healthy participants attending two clinic visits. Blood draws were performed pre-consumption and at 1, 2, and 24 h after consuming a blend of bovine colostrum- and hen’s egg-based low-molecular-weight peptides (CELMPs) versus a placebo. Immunophenotyping was performed by flow cytometry, and serum cytokines were measured by multiplex cytokine arrays. Consumption of CELMPs triggered increased immune surveillance after 1 h, involving monocytes (p < 0.1), natural killer (NK) cells (p < 0.1), and natural killer T (NKT) cells (p < 0.05). The number of NKT cells expressing the CD25 immunoregulatory marker increased at 1 and 2 h (p < 0.1). Increased serum levels of monocyte chemoattractant protein-1 (MCP-1) was observed at 2 and 24 h (24 h: p < 0.05). Selective reduction in pro-inflammatory cytokines was seen at 1, 2, and 24 h, where the 2-h reduction was highly significant for IL-6, IFN-γ, and IL-13. The rapid, transient increase in immune surveillance, in conjunction with the reduced levels of inflammatory markers, suggests that the CELMP blend of natural peptides provides immune benefits of use in preventive medicine. Further studies are warranted in chronic inflammatory conditions. Full article
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11 pages, 1055 KiB  
Article
The Antioxidant Potential of Commercial Manuka Honey from New Zealand—Biochemical and Cellular Studies
by Julia Kaźmierczak-Barańska and Bolesław T. Karwowski
Curr. Issues Mol. Biol. 2024, 46(7), 6366-6376; https://doi.org/10.3390/cimb46070380 - 25 Jun 2024
Cited by 2 | Viewed by 2463
Abstract
Manuka honey (MH) is considered a superfood mainly because of its various health-promoting properties, including its anti-cancer, anti-inflammatory, and clinically proven antibacterial properties. A unique feature of Manuka honey is the high content of methylglyoxal, which has antibacterial potential. Additionally, it contains bioactive [...] Read more.
Manuka honey (MH) is considered a superfood mainly because of its various health-promoting properties, including its anti-cancer, anti-inflammatory, and clinically proven antibacterial properties. A unique feature of Manuka honey is the high content of methylglyoxal, which has antibacterial potential. Additionally, it contains bioactive and antioxidant substances such as polyphenols that contribute to its protective effects against oxidative stress. In this study, commercially available Manuka honey was tested for its total polyphenol content and DPPH radical scavenging ability. It was then tested in vitro on human fibroblast cells exposed to UV radiation to assess its potential to protect cells against oxidative stress. The results showed that the honey itself significantly interfered with cell metabolism, and its presence only slightly alleviated the effects of UV exposure. This study also suggested that the MGO content has a minor impact on reducing oxidative stress in UV-irradiated cells and efficiency in scavenging the DPPH radical. Full article
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16 pages, 6221 KiB  
Article
Modulation of Sirtuin 3 by N-Acetylcysteine Preserves Mitochondrial Oxidative Phosphorylation and Restores Bisphenol A-Induced Kidney Damage in High-Fat-Diet-Fed Rats
by Anongporn Kobroob, Sirinart Kumfu, Nipon Chattipakorn and Orawan Wongmekiat
Curr. Issues Mol. Biol. 2024, 46(5), 4935-4950; https://doi.org/10.3390/cimb46050296 - 18 May 2024
Viewed by 3757
Abstract
Bisphenol A (BPA) and high-fat diets (HFD) are known to adversely affect the kidneys. However, the combined effects of both cases on kidney health and the potential benefits of N-acetylcysteine (NAC) in mitigating these effects have not been investigated. To explore these aspects, [...] Read more.
Bisphenol A (BPA) and high-fat diets (HFD) are known to adversely affect the kidneys. However, the combined effects of both cases on kidney health and the potential benefits of N-acetylcysteine (NAC) in mitigating these effects have not been investigated. To explore these aspects, male Wistar rats were fed with HFD and allocated to receive a vehicle or BPA. At week twelve, the BPA-exposed rats were subdivided to receive a vehicle or NAC along with BPA until week sixteen. Rats fed HFD and exposed to BPA showed renal dysfunction and structural abnormalities, oxidative stress, inflammation, and mitochondrial dysfunction, with alterations in key proteins related to mitochondrial oxidative phosphorylation (OXPHOS), bioenergetics, oxidative balance, dynamics, apoptosis, and inflammation. Treatment with NAC for 4 weeks significantly improved these conditions. The findings suggest that NAC is beneficial in protecting renal deterioration brought on by prolonged exposure to BPA in combination with HFD, and modulation of sirtuin 3 (SIRT3) signaling by NAC appears to play a key role in the preservation of homeostasis and integrity within the mitochondria by enhancing OXPHOS activity, maintaining redox balance, and reducing inflammation. This study provides valuable insights into potential therapeutic strategies for preserving kidney health in the face of environmental and dietary challenges. Full article
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14 pages, 3504 KiB  
Article
Effect of YC-1102 on the Improvement of Obesity in High-Fat Diet-Induced Obese Mice
by Hwa-Young Yu, Kyoung Kon Kim, Sin Hwa Baek, Cho I Park, Hye Jin Jeon, Ae Ri Song, Hyun-Je Park, Il Bum Park, Jong Soo Kang, Jung Min Kim, Tae Woo Kim, Sun Min Jang, Joo Young Cha and Junghyun Kim
Curr. Issues Mol. Biol. 2024, 46(2), 1437-1450; https://doi.org/10.3390/cimb46020093 - 7 Feb 2024
Cited by 1 | Viewed by 2052
Abstract
Obesity is one of the major risk factors for metabolic diseases worldwide. This study examined the effects of YC-1102, an extract derived from the roots of Rosa multiflora, on 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese mice. In vivo experiments involved the [...] Read more.
Obesity is one of the major risk factors for metabolic diseases worldwide. This study examined the effects of YC-1102, an extract derived from the roots of Rosa multiflora, on 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese mice. In vivo experiments involved the oral administration of YC-1102 (100, 150, and 200 mg/kg body weight) daily to mice for eight weeks. YC-1102 was found to downregulate the expressions of PPARγ and C/EBPα during adipogenesis, inhibiting adipocyte differentiation and upregulating the expression of PGC-1α for energy metabolism to enhance mitochondrial biogenesis and fatty acid oxidation. It has been shown that daily administration of YC-1102 to mice receiving a HFD prevented an increase in body weight and the accumulation of body fat. YC-1102 administration also reduced TG, TC, and LDL cholesterol levels, as well as glucose and leptin levels, and increased adiponectin levels, thus effectively inhibiting the metabolism of lipids. YC-1102-treated mice showed significant reductions in the mRNA expression of PPARγ and C/EBPα. The levels of PGC-1α involved in energy metabolism increased significantly in the YC-1102-treated mice when compared to the HFD-treated mice. According to the findings of this study, YC-1102 has a dual mechanism that reduces transcription factors that promote the differentiation of adipocytes and increases transcription factors that promote energy consumption. Full article
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Review

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13 pages, 435 KiB  
Review
Bridging the Gap: Supplements Strategies from Experimental Research to Clinical Applications in Sarcopenic Obesity
by Bogdana Virgolici, Maria-Zinaida Dobre and Daciana Costina Andrada Stefan
Curr. Issues Mol. Biol. 2024, 46(12), 13418-13430; https://doi.org/10.3390/cimb46120800 - 24 Nov 2024
Viewed by 849
Abstract
Obesity causes fat accumulation, and sarcopenia causes loss of muscle mass and strength; together, they worsen insulin resistance and accelerate muscle decline, creating a harmful cycle. Some supplements, along with physical exercise, could be remedies for sarcopenic obesity (SO). In this review, we [...] Read more.
Obesity causes fat accumulation, and sarcopenia causes loss of muscle mass and strength; together, they worsen insulin resistance and accelerate muscle decline, creating a harmful cycle. Some supplements, along with physical exercise, could be remedies for sarcopenic obesity (SO). In this review, we aim to draw a comparison between supplements studied in experimental research and those evaluated in clinical studies for SO. In experimental studies, Sea Buckthorn—in forms such as oil, freeze-dried powder or pomace—has been shown to enhance muscle cell growth, improve gut microbiota, provide hypoglycemic benefits and increase muscle mass by promoting protein synthesis. Increased consumption of Omega-3 fatty acids may play a protective role against SO in women. Melatonin may positively impact obesity and SO by reducing oxidative stress. Elevated irisin levels, such as those observed with vitamin D supplementation, could prevent muscle wasting and fat gain in SO by improving insulin sensitivity and reducing inflammation. There have been many studies highlighting the potential of vitamin D in preventing age related sarcopenia; however, the effect of vitamin D supplementation in SO is under-researched and appears less promising. Future clinical trials using natural supplements hold promise, as these provide multiple beneficial components that may work synergistically to treat SO. Full article
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12 pages, 431 KiB  
Review
Role of Nutrients Regulating Myeloid Derived Suppressor Cells in Cancer: A Scoping Review
by Beatriz Pérez-Peláez, Carlos Jiménez-Cortegana, Luis de la Cruz-Merino and Víctor Sánchez-Margalet
Curr. Issues Mol. Biol. 2024, 46(9), 9286-9297; https://doi.org/10.3390/cimb46090549 - 23 Aug 2024
Cited by 1 | Viewed by 1029
Abstract
Myeloid-derived suppressor cells (MDSCs) are immature cells with an immunosuppressive function. MDSCs have been related to inflammation in many settings, including infections, transplantation, obesity, aging, or cancer. In oncological settings, MDSCs participate in tumor immunoescape, growth, and metastasis. Certain nutrients can modify chronic [...] Read more.
Myeloid-derived suppressor cells (MDSCs) are immature cells with an immunosuppressive function. MDSCs have been related to inflammation in many settings, including infections, transplantation, obesity, aging, or cancer. In oncological settings, MDSCs participate in tumor immunoescape, growth, and metastasis. Certain nutrients can modify chronic inflammation by their interaction with MDSCs. Therefore, the possible influence of certain nutrients on immune surveillance by their actions on MDSCs and how this may affect the prognosis of cancer patients were evaluated in this scoping review. We identified seven papers, six of which were murine model studies and only one was a human clinical trial. Globally, a significant reduction in cancer growth and progression was observed after achieving a reduction in both MDSCs and their immunosuppressive ability with nutrients such as selected vegetables, icaritin, retinoic acid, curdlan, active vitamin D, soy isoflavones, and green tea. In conclusion, the consumption of certain nutrients may have effects on MDSCs, with beneficial results not only in the prevention of tumor development and growth but also in improving patients’ response. Full article
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Other

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10 pages, 456 KiB  
Case Report
Phytotherapy-Induced Hepatocytotoxicity: A Case Report
by Stephen Malnick, Ali Abdullah, Yaacov Maor and Manuela G. Neuman
Curr. Issues Mol. Biol. 2024, 46(7), 7548-7557; https://doi.org/10.3390/cimb46070448 - 16 Jul 2024
Viewed by 1223
Abstract
Herbal and complementary medicine are frequently integrated with conventional medicine. We aim to report a case of severe herbal-induced liver injury (HILI) due to chronic use of green tea and protein shake. We present both clinical and laboratory evidence implicating mitochondrial toxicity and [...] Read more.
Herbal and complementary medicine are frequently integrated with conventional medicine. We aim to report a case of severe herbal-induced liver injury (HILI) due to chronic use of green tea and protein shake. We present both clinical and laboratory evidence implicating mitochondrial toxicity and an immune response leading to a hypersensitivity reaction to the products. We have recently treated a 39-year-old man with hepatotoxicity resulting from a combination of a green tea-containing powder and a branched-chain amino acid supplement that was commenced 2 months previously. The hepatotoxicity resolved by stopping the consumption of these products and no other cause was detected. We decided to perform a lymphocyte toxicity assay (LTA) to determine if there was laboratory support for this diagnosis. LTA (% toxicity) represents the response of the mitochondria to toxic injury. To determine the role of the proinflammatory and anti-inflammatory cytokines and chemokines in the patient’s reaction, we measured the level of cytokines and chemokine in the media of growing cells, exposed to each product or to a combination of products. The increased cytokines and chemokines are presented as the x-fold elevations from the upper limit of normal (ULN) for matrix metalloproteinase (MMP) (pg/mL × 1.5 ULN) and interleukin (IL)-1β (pg/mL × 1.8 ULN). Higher elevations were found for interferon (IFN)-β, IFN-γ, IL-8, IL 13, IL-15 (pg/mL × 2 ULN), regulated upon activation, normal T cell expressed and presumably secreted (RANTES) (pg/mL × 2 ULN), and nuclear factor (NFκB) (pg/mL × 3 ULN). The highest increases were for vascular endothelial factor (VEGF) (pg/mL × 10 ULN), tumor necrosis factor (TNF)-α, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL × 13 ULN). An examination of cellular markers showed the difference between programmed cell death (apoptosis) and cell death due to necrosis. In our case, cytokeratin—ccK18 (M-30) U/L was within the normal limits, suggesting that apoptosis was normal, while ccK8(M65) U/L was elevated at 1.5 × ULN. This result implies that upon the treatment of the patient’s lymphocytes with the products, the mechanism of toxicity is necrosis. In susceptible individuals, the combination of protein and herbal tea produces mitochondrial toxicity and a strong T-lymphocyte-1 response, leading to HILI. There is a need of international reporting of adverse drug reactions by clinicians, laboratories, and pharmaceutical manufacturers to drug regulatory authorities. This requires internationally accepted standard definitions of reactions, as well as criteria for assessment. Full article
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