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Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention.
Li, S, Yin, S, Ding, H, Shao, Y, Zhou, S, Pu, W, Han, L, Wang, T, Yu, H
Cell proliferation. 2023;56(1):e13346
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Multiple risk factors could lead to the development of liver cancer, one of the most common malignant tumours in the world. These risk factors include hepatitis infection, non-alcoholic fatty liver disease and excessive alcohol consumption. Polyphenols are bioactive compounds with antioxidant, anti-inflammatory, anti-mutagenic, anti-viral, hypoglycaemic, anti-hypertensive, antibacterial and anti-proliferative properties. Polyphenols may be effective in reducing the risk of developing liver cancer by altering the metabolism. This review evaluated the effectiveness of polyphenols in protecting the liver and inhibiting hepatocarcinoma development. In addition, the review evaluated several mechanisms by which polyphenols affect glucose and lipid metabolism and mitochondrial metabolism and reduce the effects of oxidative stress, inflammation and toxic metabolites. Further robust studies are required to assess the beneficial effects of polyphenols as a therapeutic agent, as the current knowledge is limited. However, healthcare professionals can use the results of this study to understand the protective effects of polyphenols against liver disease.
Abstract
BACKGROUND Liver cancer is one of the common malignancies. The dysregulation of metabolism is a driver of accelerated tumourigenesis. Metabolic changes are well documented to maintain tumour growth, proliferation and survival. Recently, a variety of polyphenols have been shown to have a crucial role both in liver disease prevention and metabolism regulation. METHODS We conducted a literature search and combined recent data with systematic analysis to comprehensively describe the molecular mechanisms that link polyphenols to metabolic regulation and their contribution in liver protection and liver cancer prevention. RESULTS Targeting metabolic dysregulation in organisms prevents and resists the development of liver cancer, which has important implications for identifying new therapeutic strategies for the management and treatment of cancer. Polyphenols are a class of complex compounds composed of multiple phenolic hydroxyl groups and are the main active ingredients of many natural plants. They mediate a broad spectrum of biological and pharmacological functions containing complex lipid metabolism, glucose metabolism, iron metabolism, intestinal flora imbalance, as well as the direct interaction of their metabolites with key cell-signalling proteins. A large number of studies have found that polyphenols affect the metabolism of organisms by interfering with a variety of intracellular signals, thereby protecting the liver and reducing the risk of liver cancer. CONCLUSION This review systematically illustrates that various polyphenols, including resveratrol, chlorogenic acid, caffeic acid, dihydromyricetin, quercetin, catechins, curcumin, etc., improve metabolic disorders through direct or indirect pathways to protect the liver and fight liver cancer.
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Plasma anthocyanins and their metabolites reduce in vitro migration of pancreatic cancer cells, PANC-1, in a FAK- and NF-kB dependent manner: Results from the ATTACH-study a randomized, controlled, crossover trial in healthy subjects.
Mostafa, H, Behrendt, I, Meroño, T, González-Domínguez, R, Fasshauer, M, Rudloff, S, Andres-Lacueva, C, Kuntz, S
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023;158:114076
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Pancreatic cancer is commonly associated with poor prognosis and low overall five-year survival rate (5–7%) due to the early metastatic potential of pancreatic cancer cells. Strategies to improve the health outcomes in pancreatic cancer are challenging. The aims of this study where to investigate: - whether plasma metabolites, isolated after a 28-day intervention, would reduce migration of two pancreatic cancer cell lines (PANC-1 and AsPC-1); - whether expression of adhesion molecules on cancer and endothelial cells were influenced by plasma anthocyanins (ACN) metabolites; - which molecular mechanisms were involved; and - which metabolites in plasma and urine were altered during a long-term ACN intake and how they associate with the inhibitory effects on migration. This study is a randomised, double-blind, placebo-controlled, cross-over, 28-days intervention - ATTACH study (Anthocyanins Target Tumor cell Adhesion—Cancer vs. Endothelial Cell (HUVEC)). Thirty-five (female n = 27 and male n = 8) young, healthy volunteers participated in the intervention. Results show that ACN and metabolites isolated from plasma after a long-term ACN-rich juice intervention reduced the migration and expression of cell adhesion molecules in PANC-1 cancer cells in vitro through activation of two pathways [focal adhesion kinase- and nuclear factor kappa light chain enhancer of activated B cells (NF-kB)-pathways] as well as the reduction of reactive oxygen species. Authors conclude that their findings can lead to the investigation of interactions of ACNs with classical cancer prevention strategies.
Abstract
Pancreatic cancer is primarily considered to be a metastatic disease with a low 5-year survival rate. We aimed to detect if plasma-isolated anthocyanins and their metabolites (PAMs) modulate pancreatic cancer cells migration and to describe molecular targets of PAMs in this process. Plasma metabolites were isolated by solid-phase extraction before and after a 28-days intervention trial involving 35 healthy subjects comparing effects of a daily anthocyanin-rich juice intake vs. placebo. Plasma extracts were used for migration and mechanistic in vitro studies as well as for metabolomic analysis. Pancreatic PANC-1 and AsPC-1 were used for migration studies in a Boyden chamber co-cultured with endothelial cells. Expression of adhesion molecules on cancer and endothelial cells were determined by flow cytometry and NF-kB (nuclear factor-kappa B) p65 and focal adhesion kinase activation were measured by immunoassays. UHPLC-MS/MS metabolomics was done in plasma and urine samples. Plasma extracts isolated after the intake of the anthocyanin-rich juice significantly reduced PANC-1 migration, but not AsPC-1 migration. In PANC-1, and to a lower extent in endothelial cells, plasma extracts after juice intake decreased the expression of ß1- and ß4-integrins and intercellular adhesion molecule-1. Pooled plasma from volunteers with the highest inhibition of PANC-1 migration (n = 10) induced a reduction of NF-kB-p65 and FAK-phosphorylation in cancer and in endothelial cells. Concerning metabolites, 14 were significantly altered by juice intervention and PANC-1 migration was inversely associated with the increase of o-coumaric acid and peonidin-3-galactoside. PAMs were associated with lower PANC-1 cell migration opening new strategies for metastatic pancreatic cancer treatment.
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Resistance Exercise Training Increases Muscle Mass and Strength in Prostate Cancer Patients on Androgen Deprivation Therapy.
Houben, LHP, Overkamp, M, VAN Kraaij, P, Trommelen, J, VAN Roermund, JGH, DE Vries, P, DE Laet, K, VAN DER Meer, S, Mikkelsen, UR, Verdijk, LB, et al
Medicine and science in sports and exercise. 2023;55(4):614-624
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Androgen deprivation therapy (ADT) forms the cornerstone in the treatment of localised high-risk, locally advanced, and metastatic prostate cancer (PCa). The hypothesis of this study was that protein supplementation augments the benefits of prolonged resistance exercise training to attenuate the decline in muscle mass, reduce fat mass accrual, and increase strength and physical performance in PCa patients on ADT. This study is a multicentre partly randomised controlled trial, comparing two intervention groups with a separately recruited control group. One hundred and twenty-six patients were included, and ninety-six patients finished the study. Results show that 20 week of resistance exercise training was feasible, safe, and well tolerated, and effectively counteracted the negative effect of ADT treatment on body composition, muscle mass, leg strength, and aerobic capacity in men with advanced PCa. Protein supplementation did not further augment the benefits of resistance exercise training. Authors conclude that protein supplementation is not required to further augment gains in muscle mass and strength after resistance exercise training in PCa patients who habitually consume ample protein.
Abstract
PURPOSE This study aimed to assess the effects of 20 wk resistance exercise training with or without protein supplementation on body composition, muscle mass, muscle strength, physical performance, and aerobic capacity in prostate cancer patients receiving androgen deprivation therapy (ADT). METHODS Sixty prostate cancer patients receiving ADT were randomly assigned to perform 20 wk of resistance exercise training with supplementation of 31 g whey protein (EX + PRO, n = 30) or placebo (EX + PLA, n = 30), consumed immediately after exercise and every night before sleep. A separate control group (CON, n = 36) only received usual care. At baseline and after 20 wk, body composition (dual-energy x-ray absorptiometry), muscle mass (computed tomography scan), muscle strength (1-repetition maximum strength tests), physical performance (Timed Up and Go Test, 30-Second Chair Stand Test, and Stair Climb Test), aerobic capacity (cardiopulmonary exercise test), and habitual dietary intake (food diary) were assessed. Data were analyzed using a two-factor repeated-measures ANOVA. RESULTS Over time, muscle mass and strength increased in EX + PRO and EX + PLA and decreased in CON. Total fat mass and fat percentage increased in EX + PRO and CON, but not in EX + PLA. Physical performance did not significantly change over time in either group. Aerobic capacity was maintained in EX + PLA, but it decreased in EX + PRO and CON. Habitual protein intake (without supplements) averaged >1.0 g·kg body weight -1 ·d -1 , with no differences over time or between groups. CONCLUSIONS In prostate cancer patients, resistance exercise training counteracts the adverse effects of ADT on body composition, muscle mass, muscle strength, and aerobic capacity, with no additional benefits of protein supplementation.
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Influence of methyl donor nutrients as epigenetic regulators in colorectal cancer: A systematic review of observational studies.
Chávez-Hidalgo, LP, Martín-Fernández-de-Labastida, S, M de Pancorbo, M, Arroyo-Izaga, M
World journal of gastroenterology. 2023;29(7):1219-1234
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Colorectal cancer (CRC) is the third most frequent type of cancer and yet has the second highest mortality rate in cancer patients worldwide. Hence there is an urgency to understand more about dietary and lifestyle factors that can help to prevent this type of cancer. It is known that folate has a preventive function in CRC, possibly due to its role in DNA methylation. Methylation is the addition of methyl groups to DNA, which influences gene expression and regulation. This systematic review investigated how folate and other dietary methyl groups and methyl influencers such as B vitamins and alcohol influence the development of CRC, whilst also considering various genetic variants in methyl-metabolising enzymes (polymorphisms). The analysis included a total of 19 case-control and cohort studies and highlighted that potential interactions between methyl donor nutrients, genetic variants, and alcohol influence CRC risk. For most, high levels of folate intake were considered a protective factor, while high alcohol consumption proved to be a risk factor. Yet these interactions appear to be complex, with gender, genetic variations and folate status appearing to contribute to variable and, in some cases, contradictory outcomes. The authors suggested in their findings that Vitamin B6, Vitamin B3 (Niacin), and alcohol may affect CRC by influencing its risk by acting on both the genetic code itself and the epigenetic factors that control gene activity. Further research is needed to better understand the complexity of these mechanisms, and to help clarify the influence of methyl group donors as epigenetic regulators of gene activity in CRC development.
Abstract
BACKGROUND Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). However, whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic regulators is still unclear. AIM: To improve the current understanding of the molecular basis of CRC. METHODS A literature search in the Medline database, Reference Citation Analysis (https:// www.referencecitationanalysis.com/), and manual reference screening were performed to identify observational studies published from inception to May 2022. RESULTS A total of fourteen case-control studies and five cohort studies were identified. These studies included information on dietary methyl donors, dietary components that potentially modulate the bioavailability of methyl groups, genetic variants of methyl metabolizing enzymes, and/or markers of CpG island methylator phenotype and/or microsatellite instability, and their possible interactions on CRC risk. CONCLUSION Several studies have suggested interactions between methylenetetrahydrofolate reductase polymorphisms, methyl donor nutrients (such as folate) and alcohol on CRC risk. Moreover, vitamin B6, niacin, and alcohol may affect CRC risk through not only genetic but also epigenetic regulation. Identification of specific mechanisms in these interactions associated with CRC may assist in developing targeted prevention strategies for individuals at the highest risk of developing CRC.
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Effect of Tart Cherry on Aromatase Inhibitor-Induced Arthralgia (AIA) in Nonmetastatic Hormone-Positive Breast Cancer Patients: A Randomized Double-Blind Placebo-Controlled Trial.
Shenouda, M, Copley, R, Pacioles, T, Lebowicz, Y, Jamil, M, Akpanudo, S, Tirona, MT
Clinical breast cancer. 2022;22(1):e30-e36
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Aromatase inhibitors (AIs) are used as a treatment in breast cancer; however, a side effect of their use is often the development of aromatase inhibitor induced arthralgia (AIA), which manifests as pain in the joints, muscle weakness and reduced grip strength. Subsequently, many individuals stop taking AIs, resulting in poorer disease prognosis. Tart cherries (TC) have been shown in studies to help relieve joint pain and pain associated with exercise and so this RCT aimed to determine the effect of TC consumption on 60 breast cancer patients with AIA. The results showed that after 6-weeks individuals given TC had less pain, with some individuals reporting no pain at all. It was concluded that TC is a reliable and safe option for the management of AIA in breast cancer patients. This study could be used by healthcare professionals to recommend TC as an adjunct to aromatase inhibitor therapy in individuals with breast cancer who are experiencing pain.
Abstract
BACKGROUND Aromatase Inhibitor induced Arthralgia (AIA) can cause noncompliance leading to decreased breast-cancer survival. Effective interventions for AIA are limited. Tart cherry (TC) showed beneficial effect on musculoskeletal pain. 48 patients (Pts) randomized to TC versus placebo over 6 weeks, TC (23pts) had 34.7% mean pain decrease versus 1.4% in Placebo (25pts). TC can improve AIA in nonmetastatic breast-cancer patients. METHODS Randomized, placebo-controlled, double-blind trial. Eligible patients with NMHPBC on AI for at least 4 weeks were randomized to TC concentrate [50 tart cherries] vs. placebo (P) [syrup] in 1:1 model. Patients instructed to consume 1 Oz of concentrate in 8 Oz water daily for 6 weeks, and document their pain intensity at baseline, weekly and at study completion in a diary using Visual Analog Scale (VAS), with 0 mm indicating no pain, and 100 mm indicating highest pain. RESULTS Sixty patients were enrolled. Two patients did not complete the study due to diarrhea, and 10 patients were noncompliant. Forty-eight patients were included in the final analysis. TC group (23 pts) had 34.7% mean decrease in pain compared to 1.4% in P group (25 pts). This difference was statistically significant (Mann-Whitney U Test, P = .034). CONCLUSIONS Tart cherry can significantly improve AIA in nonmetastatic breast cancer patient.
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Mycotoxin-Linked Mutations and Cancer Risk: A Global Health Issue.
Ekwomadu, T, Mwanza, M, Musekiwa, A
International journal of environmental research and public health. 2022;19(13)
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Mycotoxins are toxic substances produced by fungi, which can be found in common foods like maize, wheat, nuts, and foods containing them. Mycotoxins such as aflatoxins, ochratoxin, fumonisins, zearalenone, and some Penicillium toxins can alter genetic material. According to previous studies, they can damage genetic material and affect cell growth. Usage of chemicals such as fertilizers and fungicides is a common practice in the agricultural industry to protect plants from fungus and to feed them. However, fungicides can accelerate mycotoxin production. 16 studies were included in this Systematic Review and 11 in Meta-Analysis. This research looked at the harmful effects of mycotoxins such as aflatoxins, fumonisins, ochratoxin, T2, zearalenone, and some Penicillium toxins in causing cancers. The researchers evaluated the link between aflatoxin exposure and liver cancer, fumonisin B1 exposure and liver cancer, zearalenone exposure and breast cancer, zearalenone exposure and cervical cancer, citrinine and patulin exposure and colorectal cancer, and NEO, HT-2, and T-2 exposure and Oesophageal cancer. This research did not show significant associations between various mycotoxins and cancer risk. As currently, most studies are primarily focused on aflatoxin; more robust studies are needed to assess the cancer risk associated with different mycotoxin exposure. Using the results of this study, healthcare professionals can gain a better understanding of how mycotoxins affect our bodies.
Abstract
Humans continue to be constantly exposed to mycotoxins, mainly through oral exposure (dietary), inhalation, or dermal contact. Recently, it has been of increasing interest to investigate mycotoxin-linked carcinogenicity. This systematic review was conducted to synthesize evidence of the association between mycotoxin-linked mutations and the risk of cancer, to provide an overview of the data linking exposure to different mycotoxins with human cancer risk, and to provide an update on current research on the risk of cancer associated with human exposure to mycotoxins. PRISMA guidelines were used when conducting the systematic review. PubMed, MEDLINE, and CINAHL electronic databases were comprehensively searched to extract the relevant studies published from inception to May 2022. A total of sixteen relevant studies (4907 participants) were identified and included in this review. Of these, twelve studies were from Asia, while four of the studies were conducted in Africa. The overall meta-analysis result found no significant association, although some of the studies confirmed an association between mycotoxin-linked mutations and primary liver cancer risk. Mainly, the experimental studies have shown associations between mycotoxin-linked mutations and cancer risk, and there is a need for researchers to confirm these links in epidemiological studies in order to guide public health policies and interventions.
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Consumption of industrial processed foods and risk of premenopausal breast cancer among Latin American women: the PRECAMA study.
Romieu, I, Khandpur, N, Katsikari, A, Biessy, C, Torres-Mejía, G, Ángeles-Llerenas, A, Alvarado-Cabrero, I, Sánchez, GI, Maldonado, ME, Porras, C, et al
BMJ nutrition, prevention & health. 2022;5(1):1-9
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Ultra-processed food intake has been linked to an increased risk of breast cancer in Western populations. This is the first study on ultra-processed food and breast cancer in young women from Latin America. In Latin America around 27% of breast cancers occur between 20 and 45 years and this is increasing. This population is currently undergoing rapid lifestyle and nutritional changes switching from a varied traditional diet (including corn tortillas, corn flour cakes, beans and other legumes, soup, homemade stew, vegetable, whole fruit) towards a more homogenous diet rich in industrial ultra-processed foods. In this case control study, the association of ultra-processed food intake to breast cancer risk was evaluated. 525 cases were included (women aged 20–45 years) and 525 matched population-based controls from Chile, Colombia, Costa Rica and Mexico. The degree of processing of foods was classified according to the NOVA classification. The results show an adverse effect of ultra-processed food intake on the risk of breast cancer in young Latin American women. Further studies are needed to confirm the results. Given the already proven chronic adverse health effects of ultra-processed foods, a decrease in these types of foods should be encouraged.
Abstract
Ultra-processed food intake has been linked to an increased risk of breast cancer in Western populations. No data are available in the Latin American population although the consumption of ultra-processed foods is increasing rapidly in this region. We evaluated the association of ultra-processed food intake to breast cancer risk in a case-control study including 525 cases (women aged 20-45 years) and 525 matched population-based controls from Chile, Colombia, Costa Rica and Mexico. The degree of processing of foods was classified according to the NOVA classification. Overall, the major contributors to ultra-processed food intake were ready-to-eat/heat foods (18.2%), cakes and desserts (16.7%), carbonated and industrial fruit juice beverages (16.7%), breakfast cereals (12.9%), sausages and reconstituted meat products (12.1%), industrial bread (6.1%), dairy products and derivatives (7.6%) and package savoury snacks (6.1%). Ultra-processed food intake was positively associated with the risk of breast cancer in adjusted models (OR T3-T1=1.93; 95% CI=1.11 to 3.35). Specifically, a higher risk was observed with oestrogen receptor positive breast cancer (ORT3-T1=2.44, (95% CI=1.01 to 5.90, P-trend=0.049), while no significant association was observed with oestrogen receptor negative breast cancer (ORT3-T1=1.87, 95% CI=0.43 to 8.13, P-trend=0.36). Our findings suggest that the consumption of ultra-processed foods might increase the risk of breast cancer in young women in Latin America. Further studies should confirm these findings and disentangle specific mechanisms relating ultra-processed food intake and carcinogenic processes in the breast.
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The Effect of Omega-3 Enriched Oral Nutrition Supplement on Nutritional Indices and Quality of Life in Gastrointestinal Cancer Patients: A Randomized Clinical Trial.
Sim, E, Kim, JM, Lee, SM, Chung, MJ, Song, SY, Kim, ES, Chun, HJ, Sung, MK
Asian Pacific journal of cancer prevention : APJCP. 2022;23(2):485-494
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Cancer cachexia is a multifactorial condition that reveals impairments in energy and protein balance leading to weight loss through the loss of skeletal muscle and body fat. Nutritional status of cancer patients affects therapeutic efficacy, and the disease survival is influenced by the degree of anorexia. The aim of this study was to evaluate the efficacy of omega-3 fatty acids fortified nutrition supplement intervention on nutritional status, quality of life (QOL) and pro-inflammatory cytokine concentrations of cancer patients. This study was a randomised controlled study. Participants (n = 58) included in the study were patients who were in stages between II to IV receiving one or more cancer therapies without taking any nutritional supplements. Both control and experimental groups received regular nutrition counselling and education, while only the experimental group was asked to take oral nutrition supplements (ONS) twice a day (400 ml, 400 kcal). Results show that ONS intervention: - alleviated symptoms of gastrointestinal symptoms including nausea, vomiting and constipation; - exerted improvements in many of QOL indices; and - did not improve (statistically significant) biochemical markers of nutritional status and concentration level of pro-inflammatory cytokines. Authors conclude that nutritional supplements can improve some of the QOL components which need evidence-based explanation in mechanistic aspects.
Abstract
OBJECTIVE Gastrointestinal (GI) cancer patients often experience severe malnutrition during cancer therapies due to gastrointestinal dysfunctions including poor digestion and absorption as well as tumor-associated anorexia. In this study, we performed a randomized clinical trial to determine the efficacy of oral nutrition supplement (ONS) enriched with omega-3 fatty acids on nutritional status, quality of life (QOL), and pro-inflammatory indices. METHODS Patients diagnosed with GI cancers were recruited and screened for eligibility. A total of 58 patients were randomly allocated to either the control group (n=27) or the experimental group (n=31). The intervention group received 200 ml ONS twice a day while the control group received routine care. Anthropometrics, Patient-Generated Subjective Global Assessment (PG-SGA) score, QOL score and nutrient intake data were collected at baseline, week 4 and week 8. Blood was drawn for biochemical assessments. Nine patients from each group dropped out of the study Forty patients (18 control patients and 22 intervention patients) completed the study. RESULTS This study showed that ONS intervention improved PG-SGA scores in the intervention group (p<0.01). Scores of physical functioning score and role functioning were declined only in the control group and the difference between week 8 and baseline for role functioning was significant (p<0.001). Fatigue score was steadily decreased in the experiment group, and the differences between week 8 and baseline was significant between two groups (p<0.02). However, no statistically significant improvement in biochemical markers of nutritional status and pro-inflammatory cytokine concentrations were found. These results suggests that ONS intervention for 8 weeks improves PG-SGA scores and QOL scores in patients undergoing cancer therapy.
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Improving health-related quality of life in women with breast, blood, and gynaecological Cancer with an eHealth-enabled 12-week lifestyle intervention: the women's wellness after Cancer program randomised controlled trial.
Seib, C, Anderson, D, McGuire, A, Porter-Steele, J, McDonald, N, Balaam, S, Sapkota, D, McCarthy, AL
BMC cancer. 2022;22(1):747
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Aging populations and the increased prevalence of other cancer risk factors have led to an increased incidence of cancer in women globally. Cancer treatments often leave women with a range of residual physical and psychological side effects. Comprehensive cancer rehabilitation can reduce symptom burden and health service utilisation, whilst generally improving health-related quality of life (HRQOL). The primary aim of this study was to test the efficacy of a multimodal, digitised lifestyle intervention on HRQOL of women treated for cancer. This study is a multi-centre, single-blinded, randomised controlled 12-week trial. Fifty-one women previously treated for breast, blood or gynaecological cancer were randomly assigned to either an intervention or usual care arm. Results indicate improvements in many HRQoL domains and in component summary scores. Particularly notable were the improvements in general health and bodily pain, vitality, mental health, and global physical and mental health summary scores among women in the intervention group. Authors conclude that the complex and synergistic effects of many modifiable health behaviours emphasise the need for bundled health behaviour interventions to optimise women’s health and wellbeing after completion of active cancer treatment.
Abstract
BACKGROUND The residual effects of cancer and its treatment can profoundly affect women's quality of life. This paper presents results from a multisite randomized controlled trial that evaluated the clinical benefits of an e-health enabled health promotion intervention (the Women's Wellness after Cancer Program or WWACP) on the health-related quality of life of women recovering from cancer treatment. METHODS Overall, 351 women previously treated for breast, blood or gynaecological cancers were randomly allocated to the intervention (WWACP) or usual care arms. The WWACP comprised a structured 12-week program that included online coaching and an interactive iBook that targeted physical activity, healthy diet, stress and menopause management, sexual wellbeing, smoking cessation, alcohol intake and sleep hygiene. Data were collected via a self-completed electronic survey at baseline (t0), 12 weeks (post-intervention, t1) and 24 weeks (to assess sustained behaviour change, t2). The primary outcome, health-related quality of life (HRQoL), was measured using the Short Form Health Survey (SF-36). RESULTS Following the 12-week lifestyle program, intervention group participants reported statistically significant improvements in general health, bodily pain, vitality, and global physical and mental health scores. Improvements were also noted in the control group across several HRQoL domains, though the magnitude of change was less. CONCLUSIONS The WWACP was associated with improved HRQoL in women previously treated for blood, breast, and gynaecological cancers. Given how the synergy of different lifestyle factors influence health behaviour, interventions accounting for the reciprocity of multiple health behaviours like the WWACP, have real potential for immediate and sustainable change. TRIAL REGISTRATION The protocol for this randomised controlled trial was submitted to the Australian and New Zealand Clinical Trials Registry on 15/07/2014 and approved on 28/07/2014 ( ACTRN12614000800628 ).
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A Double-Blind, Placebo-Controlled Randomized Phase IIa Study: Evaluating the Effect of Curcumin for Treatment of Cancer Anorexia-Cachexia Syndrome in Solid Cancer Patients.
Chaiworramukkul, A, Seetalarom, K, Saichamchan, S, Prasongsook, N
Asian Pacific journal of cancer prevention : APJCP. 2022;23(7):2333-2340
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Cancer anorexia–cachexia syndrome (CACS) is usually found in advanced cancer patients. CACS is a multifactorial process which comprises skeletal muscle and adipose tissue loss which may be compounded by anorexia and a dysregulated metabolic state. The hypothesis of this study was that curcumin will increase body compositions and body weight in patients with solid malignancy and CACS when compared to placebo after adjusting by age, gender, primary site of cancer, stage of cancer, performance status, and supplementary nutrition support. This study was a double-blind, placebo-controlled randomised phase lla study. A total of 46 patients were enrolled, of whom 33 underwent 1:1 block of four randomisations. Seventeen patients were randomly assigned to receive curcumin at dose of 800 mg twice daily orally and sixteen patients were randomly assigned to received placebo. Results show that curcumin supplementation: (1) did not statistically significantly improve body compositions and body weight when compared to placebo; (2) may cause clinical benefit in term of hand grip muscle strength and slow progress of CACS by decreasing in basal metabolic rate and preventing the decline in serum albumin; and (3) administered orally for two months at a dose of up to 2 grams daily appeared safe and no serious adverse events were reported. Authors conclude that curcumin inhibited process of CACS via reduction of basal metabolic rate and slowed down the progression of hand-grip muscle strength loss. Furthermore, nuclear factor kappa B [regulator of gene expression] levels merit further exploration as potentially suitable predictive biomarker for CACS treatment with curcumin.
Abstract
OBJECTIVE We aim to investigate the effect of curcumin on preventing cancer anorexia-cachexia syndrome (CACS) via through mechanism of inhibition on NF-kB signal pathway. Outcome measurement for primary end point was improvement of body tissue composition, and the secondary end points were body weight and body mass index, hand grip muscle strengthening, and safety. METHODS This is randomized, double-blind, placebo-controlled phase ll a study, 33 patients with CACS in solid malignancy were enrolled and randomized in 1:1 to receive oral curcumin (at a dose of 800 mg twice daily) or placebo for 8 weeks. RESULTS All parameters of body compositions were not statistically significant different between two groups, which were consist body fat mass [-1.25(SEM 0.87) vs. +0.63(SEM 0.55); p=0.119], skeletal muscle mass [-0.35(SEM 0.60) vs.+0.33(SEM 0.42); p=0.408] and percent body fat [-0.47(SEM 0.95) vs. -0.29(SEM 0.82); p=0.893] including with basal metabolic rate [-13.47(SEM 21.94) vs. +15.30(13.76); p=0.336]. The average of weight loss was also not statistically significant different between two groups. [-1.4 kg(SEM 0.89) in curcumin vs-1.12 kg(SEM 0.73), p=0.810]. Notably, patient with curcumin had less reduction of hand-grip muscle strength on both hands [Rt. handed: -2.47 in curcumin vs. -5.36 in placebo; p=0.318] [Lt. handed: -1.98 vs. -5.43; p=0.317], and basal metabolic rate than placebo group. Most adverse events were grade 1 on both groups similarly. CONCLUSION Curcumin was not shown to be superior to placebo with regard to increasing the body composition in cancer patients with CACS. However, curcumin might show some clinical benefits, including slow progression of hand-grip muscle strength loss, and basal metabolic rate. Further investigations should be explored.