Dietary Means Research Articles

Cancer, Coma, Chromosomes, and the Comforter: Investigating Scientific Mechanisms of Divine Healing and Design

While narratives of divine healing are common, we rarely encounter scientific investigations into divine healing presented to the scientist, the theologian, and the curious alike. This research begins by highlighting the brilliance of the design of the human body that has been intricately fine-tuned through the work of the Holy Spirit (HS) to resist disease. The study discusses how creation harbors plant-derived bioactive molecules strategically placed to safeguard and heal the body of certain cancers and other diseases through dietary means–a testament to the design and protective work of the HS intricately woven into nature. The study also scientifically investigates divine healing by examining evidence-based data on significant cases from medical records and scientific literature. We investigate cases of remarkable divine healings from metastatic cancer, inherited genetic disease, cardiac arrest, and coma in response to prayer for healing after modern medicine offered no permanent solution.

Leonurine as a dietary compound: Its role in ferroptosis inhibition through Nrf2 signaling pathway activation

This research explores the potential of leonurine, a component found in motherwort, to inhibit intestinal inflammatory response in patients of inflammatory bowel disease (IBD) through dietary means with a particular emphasis on how it influences the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Using colon epithelial cell lines, HT29 and Caco-2, we set up models to study the impact of inflammation, oxidative stress, and apoptosis induced by lipopolysaccharide (LPS). In addition, we employed Nrf2 knockout cell lines to understand its function in a better way. The introduction of leonurine is aimed to evaluate its ability to reduce cell damage and inflammatory reactions by activating the Nrf2–heme oxygenase-1 (HO-1) pathway. Results indicated that LPS exposure led to inflammation, oxidative stress, apoptosis, and potential ferroptosis. It was observed that Nrf2 acted as a suppressor in this scenario; its absence increased cell susceptibility to these challenges. Treatment with leonurine notably decreased inflammation, oxidative stress, and apoptosis; however, these protective effects were significantly reduced in cells lacking Nrf2. This confirms that leonurine can inhibit oxidative stress, inflammatory response, apoptosis, and potential ferroptosis mechanism of colon epithelial cells by activating Nrf2. This study not only enhances our understanding of how leonurine regulates IBD but also highlights the importance of Nrf2 by shedding light on IBD development and potential nutritional approaches for its management.

The protective effects of Kefir extract (KE) on intestinal damage in larval zebrafish induced by Oxytetracycline: Insights into intestinal function, morphology, and molecular mechanisms

The antibiotic oxytetracycline (OTC) can be detected in contemporary natural aquatic environments and has been implicated in causing intestinal damage in humans exposed to OTC-contaminated food or water. The irreversible damage caused by high concentrations of OTC to the intestine suggests that treatment through dietary means could still be necessary. This study proved the effectiveness of kefir extract (KE) in reversing intestinal damage caused by oxytetracycline (OTC) exposure. Following a 24-hour KE treatment subsequent to OTC exposure from 3 to 8 days post-fertilization of zebrafish larvae, molecular-level and microbiomic assessments revealed significant improvements. These included reduced expression of proinflammatory factors (IL-8 and IL-1β), increased antioxidant levels, and reversed unhealthy distribution of intestinal microbiota. Furthermore, KE supplementation showed potential in enhancing intestinal motility in the experiment of Nile red staining and fluorescent microbead transit. However, histological analysis showed that this short-term treatment with KE only partially reversed the intestinal morphological changes induced by OTC, suggesting that a longer treatment period might be necessary for complete restoration.

Intestinal microbial diversity in domestic honey bees and evaluation of their probiotic properties

As populations of managed honey bees in various regions increase in comparison to wild colonies, there is a need to ensure that threats to bee health and survival in all environments are countered. One of the more direct methods of approaching bee health is through dietary means and as such, we investigated the intestinal microbial diversity in the gut of honey bees in order to identify strains with probiotic potential. Honey bees were fed with several feeds including Feedbee, Megabee, sugar syrup 60% (w/v), Yangbongnonghyup (YBNH), and Test A, to monitor the culture-dependent and culture-independent microbial diversity. In the culture-dependent study, most isolates belonged to Apilactobacillus (24.1%), Fructobacillus (21.8%), and Bacillus (15.4%) at the genus level. Culture-independent results showed that Bacillota and Pseudomonadota were the most abundant groups (99%) among the gut bacteria, while other bacteria showed a lower percentage than 0.1%. Next, the hydrolytic enzymes (α-amylase, protease, and cellulase) and antibacterial and antioxidant activities of the isolated strains were evaluated to examine their applicability as potential probiotics for honey bees. The selected strains showing three hydrolytic enzyme activities were used to determine their antibacterial activity against Paenibacillus larvae. Bacillus subtilis MBLB2796 showed the highest α-amylase (1.24 ± 0.06 U/mL) and cellulase (0.24 ± 0.01 U/mL) activities while B. tequilensis MBLB2834 exhibited the highest protease activity (0.15 ± 0.03 mU/mL) and the highest antioxidant activity (71.0 ± 3.8%). This study suggests that honey bee gut-originated isolates are prime candidates for use as probiotics in honey bees.

Abstract 770: The innate immune system response to malignancy- under the radar

Abstract It has become clear that many cancers evade detection by, for example, silencing of immune checkpoints. Re-activation of the immune armamentarium by checkpoint inhibitors has improved survival in many types of cancer. However, we still are unable to gauge the response of the innate immune system (InImS) to incipient malignancy. The InImS is likely both a sentient early warning system and an immediately deployed cancer combatant. We describe a potential marker that quantifies the innate immune system response to multiple deadly tumors. Methods: We obtained a database of patients at high risk of colorectal neoplasia and prospectively noted those who contracted cancer on follow up. We contrasted the historic, premorbid biomarker response from the time of enrolment, primarily using the FERAD ratio. This was obtained by dividing the ferritin blood concentration by the denominator of fecal shedding of a Paneth cell marker, p87. We also compared the FERAD response to the absolute neutrophil:lymphocyte ratio (NLR), a known prognostic biomarker, and also the available, known PDL-1 response for each group of cancers. Results: We found that certain groups of cancers historically had very low FERAD ratios while others were high. Using FERAD ratios for lung, gastric, non-Hodgkin’s lymphoma, melanoma, thyroid, renal, and head and neck cancers, there is a significant inverse correlation between survival and FERAD (r=-0.8;p<0.025) which is similar to that of NLR (r=-0.7;p<0.035). For prostate cancer, breast, colorectal cancer (CRC), leukemia/MDS, there is a direct correlation between survival and FERAD (r=0.99;p<0.002). There is also an inverse relationship between NLR and PDL-1 response rates (r=-0.8;p<0.04). An observed mild positive trend for FERAD PDL-1 response rates may bode well for melanoma, lung, head and neck and renal cancers. Conclusions: Since p87 could be manipulated by dietary means to affect the FERAD ratio favorably, this could be incorporated into more effective chemotherapy regimens and result in better cancer treatment outcomes. Hepatocellular cancer (HCC) and CRC-liver metastasis appear to be immunological outliers. This will need an additional unique approach such as TIGIT intervention therapy (Zheng et al.. Immune checkpoint targeting TIGIT in HCC. Am J Transl Res. 2020). This may allow modulation of the immune response based on FERAD, NLR ratios, and other considerations of mutational burden and genetic mutations, in patients with selected cancers. Citation Format: Martin Tobi, Harvinder Talwar, Benita McVicker. The innate immune system response to malignancy- under the radar [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 770.

Unraveling florfenicol's effects on splenic histology, erythrocytes, and hematology of healthy Oreochromis niloticus juveniles

AbstractThe study aimed to investigate the impact of administering the antibiotic florfenicol (FFC) through dietary means on Oreochromis niloticus. The experiment involved exposing the fish to FFC at doses 0–10 times the therapeutic dose of 15 mg/kg biomass per day for 10 consecutive days. The group receiving the therapeutic dose showed 100% survival on the 10th day of dosing. Histological analysis revealed dose‐dependent changes in the spleen, including an increase in sinusoidal space, splenic necrosis, white pulp proliferation, splenitis, and red pulp hemorrhages. Additionally, there was an exponential rise in leukocyte counts accompanied by a significant decrease in erythrocyte counts, indicating the development of anemia due to FFC. The observed splenic histological damage, along with increased erythrophagia, erythro‐membrane breakage, and poikilocytosis, highlighted the splenotoxic and hemotoxic effects of FFC at higher doses. Importantly, these toxic effects showed considerable reduction upon discontinuation of FFC dosing. The study emphasized the need to consider FFC‐induced splenotoxic and hemotoxic outcomes in O. niloticus during its application in aquaculture.

Hydroxylated Tetramethoxyflavone Affects Intestinal Cell Permeability and Inhibits Cytochrome P450 Enzymes.

Tetramethoxyflavones (TMFs) found in the Citrus genus have garnered considerable interest from food scientists and the health food industry because of their promising biological properties. Nonetheless, there are currently limited data available regarding the effectiveness and bioavailability of "hydroxylated TMFs", which are flavones known for their potential in disease prevention through dietary means. This study aims to provide insights into the chemical and biological properties of hydroxylated TMF and evaluates its effects on intestinal cell permeability and cytochrome P450 (CYP) inhibition. Liquid chromatography-mass spectrometry (LC-MS) and microsomes analyze the TMFs and hydroxylated TMFs, elucidating cell penetration and metabolic inhibition potential. 3H7-TMF shows the fastest (1-h) transport efficiency in intestinal cells. The Caco-2 cell model exhibits significant transport and absorption efficiency. Dissolved hydroxyl-TMF with hydrophilicity possibly permeates the gut. 3H7-TMF has higher transport efficiency (46%) 3H6-TMF (39%). IC50 values of TMFs (78-TMF, 57-TMF, 3H7-TMF, 3H6-TMF) against CYP enzymes (CYP1A2, CYP2D6, CYP2C9, CYP2C19, CYP3A4) range from 0.15 to 108 μM, indicating potent inhibition. Hydroxyl groups enhance TMF hydrophilicity and membrane permeability. TMFs display varied inhibitory effects due to hydroxyl and methoxy hindrance. This study underscores the strong CYP inhibitory capabilities in these TMFs, implying potential food-drug interactions if used in medicines or supplements. These findings can also help with food nutrition improvement and pharma food developments through innovative approaches for Citrus waste valorization.

All Roads Lead to the Gut: The Importance of the Microbiota and Diet in Migraine.

Migraine, a prevalent neurological condition and the third most common disease globally, places a significant economic burden on society. Despite extensive research efforts, the precise underlying mechanism of the disease remains incompletely comprehended. Nevertheless, it is established that the activation and sensitization of the trigeminal system are crucial during migraine attacks, and specific substances have been recognized for their distinct involvement in the pathomechanism of migraine. Recently, an expanding body of data indicates that migraine attacks can be prevented and treated through dietary means. It is important to highlight that the various diets available pose risks for patients without professional guidance. This comprehensive overview explores the connection between migraine, the gut microbiome, and gastrointestinal disorders. It provides insight into migraine-triggering foods, and discusses potential diets to help reduce the frequency and severity of migraine attacks. Additionally, it delves into the benefits of using pre- and probiotics as adjunctive therapy in migraine treatment.

β(2 → 1)-β(2 → 6) and β(2 → 1) fructans protect from impairment of intestinal tight junction's gene expression and attenuate human dendritic cell responses in a fructan-dependent fashion

β(2 → 1)-β(2 → 6) branched graminan-type fructans (GTFs) and β(2 → 1) linear fructans (ITFs) possess immunomodulatory properties and protect human intestinal barrier function, however the mechanisms underlying these effects are not well studied. Herein, GTFs and ITFs effects with different degree of polymerization (DP) values on tight junctions (TJs) genes CLDN-1, -2 and -3, CDH1, OCLN and TJP1 were studied in Caco-2 gut epithelial cells, under homeostatic and inflammatory conditions. Also, cytokine production in dendritic cells (DCs) was studied. Higher DP fructans decreased the expression of the pore forming CLDN-2. Higher DP GTFs enhanced CLDN-3, OCLN, and TJP-1. Fructans prevented mRNA dysregulation of CLDN-1, -2 and -3 induced by the barrier disruptors A23187 and deoxynivalenol in a fructan-type dependent fashion. The production of pro-inflammatory cytokines MCP-1/CCL2, MIP-1α/CCL3 and TNFα by DCs was also attenuated in a fructan-type dependent manner and was strongly attenuated by DCs cultured with medium of Caco-2 cells which were pre-exposed to fructans. Our data show that specific fructans have TJs and DCs modulating effects and contribute to gut homeostasis. This might serve to design effective dietary means to prevent intestinal inflammation.

Sustained oral spermidine supplementation rescues functional and structural defects in COL6-deficient myopathic mice

ABSTRACT COL6 (collagen type VI)-related myopathies (COL6-RM) are a distinct group of inherited muscle disorders caused by mutations of COL6 genes and characterized by early-onset muscle weakness, for which no cure is available yet. Key pathophysiological features of COL6-deficient muscles involve impaired macroautophagy/autophagy, mitochondrial dysfunction, neuromuscular junction fragmentation and myofiber apoptosis. Targeting autophagy by dietary means elicited beneficial effects in both col6a1 null (col6a1 –/– ) mice and COL6-RM patients. We previously demonstrated that one-month per os administration of the nutraceutical spermidine reactivates autophagy and ameliorates myofiber defects in col6a1 –/– mice but does not elicit functional improvement. Here we show that a 100-day-long spermidine regimen is able to rescue muscle strength in col6a1 –/– mice, with also a beneficial impact on mitochondria and neuromuscular junction integrity, without any noticeable side effects. Altogether, these data provide a rationale for the application of spermidine in prospective clinical trials for COL6-RM. Abbreviations: AChR: acetylcholine receptor; BTX: bungarotoxin; CNF: centrally nucleated fibers; Colch: colchicine; COL6: collagen type VI; COL6-RM: COL6-related myopathies; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; NMJ: neuromuscular junction; Spd: spermidine; SQSTM1/p62: sequestosome 1; TA: tibialis anterior; TOMM20: translocase of outer mitochondrial membrane 20; TUNEL: terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling.

The Hypoglycemic and Hypolipidemic Effects of Polyphenol-Rich Strawberry Juice on Diabetic Rats.

Obesity and diabetes are some of the most important modern health problems requiring simple preventative or palliative measures using dietary means. This study investigated the impact of strawberry juice on diabetic rats. Diabetes was induced in rats using a single intraperitoneal injection of 50mg/kg streptozotocin (STZ). Fifty male rats were divided into five groups: normal control (NC), strawberry juice only (S), diabetic control (DC), and two diabetic groups treated with strawberry juice (DC + S) or metformin (DC + met). Rats were administered a single dose of both strawberry juice and oral metformin, and biochemical and histological analyses were conducted. The experiment was conducted in compliance with the Ethics Committee's regulations for the care and utilization of animals, microorganisms, and living cell cultures in education and scientific research at the Faculty of Agriculture, Minia University (MU/FA/006/12/22). Treatment of diabetic rats with strawberry juice led to a significant decrease in blood glucose. Insulin levels were also significantly increased, while lipid profiles were lowered in the diabetic rats treated with strawberry juice. Carbohydrate metabolism enzymes and antioxidant enzyme activities in the treated rats were restored to normal levels, and the levels of lipid peroxidation and proinflammatory cytokines were notably reduced. The microstructure of pancreatic and liver cells in diabetic rats was also improved with strawberry juice treatment. In addition, HPLC analysis revealed that strawberry juice was rich in flavonoids and phenolic compounds and exhibited potent antioxidant activity. These findings suggest that strawberry juice has considerable hypoglycemic and hypolipidemic effects on rats with diabetes which may be used in human after further investigations.

Hepatic hydrogen sulfide levels are reduced in mouse model of Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare human disease characterised by accelerated biological ageing. Current treatments are limited, and most patients die before 15 years of age. Hydrogen sulfide (H2S) is an important gaseous signalling molecule that it central to multiple cellular homeostasis mechanisms. Dysregulation of tissue H2S levels is thought to contribute to an ageing phenotype in many tissues across animal models. Whether H2S is altered in HGPS is unknown. We investigated hepatic H2S production capacity and transcript, protein and enzymatic activity of proteins that regulate hepatic H2S production and disposal in a mouse model of HGPS (G609G mice, mutated Lmna gene equivalent to a causative mutation in HGPS patients). G609G mice were maintained on either regular chow (RC) or high fat diet (HFD), as HFD has been previously shown to significantly extend lifespan of G609G mice, and compared to wild type (WT) mice maintained on RC. RC fed G609G mice had significantly reduced hepatic H2S production capacity relative to WT mice, with a compensatory elevation in mRNA transcripts associated with several H2S production enzymes, including cystathionine-γ-lyase (CSE). H2S levels and CSE protein were partially rescued in HFD fed G609G mice. As current treatments for patients with HGPS have failed to confer significant improvements to symptoms or longevity, the need for novel therapeutic targets is acute and the regulation of H2S through dietary or pharmacological means may be a promising new avenue for research.

TRPV4 functional status in cystic cells regulates cystogenesis in autosomal recessive polycystic kidney disease (ARPKD) during variations in dietary potassium

Mechanosensitive Ca2+-permeable transient receptor potential vanilloid type 4 (TRPV4) channel plays a dominant role in maintaining intracellular Ca2+ ([Ca2+]i) homeostasis and flow-sensitive [Ca2+]i signaling in the distal segments of renal tubule and collecting duct. Polycystic kidney disease (PKD) manifests as progressive cyst growth with cystic cells exhibiting exacerbated cAMP-dependent fluid secretion along with deficient mechanosensitivity and reduced basal [Ca2+]i levels, and impaired TRPV4 activity. In this study, we tested how regulation of renal TRPV4 function by elevated dietary K+ intake modulates the rate of cystogenesis and mechanosensitive [Ca2+]i signaling in cystic cells of PCK453 rats (1 m.o.), a homologous model of human autosomal recessive PKD (ARPKD), where cyst development is restricted to the collecting duct. One month treatment with both high KCl (5% K+) and KB/C (5% K+ with bicarbonate to citrate in 4:1 ratio) diets significantly increased kidney TRPV4 levels in PCK453 rats when compared to the control group fed regular diet (0.9% K+). High KCl diet also caused an increased TRPV4-dependent Ca2+ influx, higher basal [Ca2+]i, and partial restoration of mechanosensitivity in freshly isolated monolayers of cystic cells. Unexpectedly, high KB/C diet induced an opposite effect by reducing TRPV4 activity and further worsening [Ca2+]i homeostasis. Importantly, high KCl diet decreased, whereas high KB/C diet further increased cAMP levels, as was assessed by the extent of cAMP-dependent translocation of AQP2 water channel to apical membrane in cystic cells. At the systemic level, high KCl diet fed PCK453 rats had significantly lower kidney-to-bodyweight ratio and reduced cystic area in renal sections. The beneficial effects of high KCl diet were negated by a concomitant administration of an orally active TRPV4 antagonist, GSK2193874, resulting in greater kidney weight and accelerated cystogenesis, when compared to these values in control rats. In a similar manner, high KB/C diet exacerbated renal manifestations of ARPKD, consistent with deficient TRPV4 activity in cystic cells. Moreover, KCl+GSK2193874 and high KB/C treated PCK453 rats have increased urinary levels of a renal injury marker, KIM-1.In conclusion, we demonstrate that TRPV4 channel activity negatively regulates cAMP levels in cystic cells upon variations in K+ intake thus attenuating (high activity) or accelerating (low activity) ARPKD progression in PCK453 rats. We propose that pharmacological or dietary means leading to TRPV4 stimulation might be useful to counteract PKD progression in the clinical setting. This research was supported by NIH-NIDDK DK117865, DK119170, AHA EIA35260097 (to O. Pochynyuk) and AHA-19CDA34660148 (to V. N. Tomilin). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Metabolic correction of neurodegenerative pathologies: the role of macronutrients and timing

Despite decades of intensive research, effective treatment and prevention strategies for neurodegenerative diseases (NDDs) remain elusive. This review focuses on Alzheimer’s and Parkinson’s diseases and acquired epilepsy suggesting that in their early phase, these progressive pathologies share common or interacting molecular pathways. Indeed, oxidative stress associated with disrupted glucose metabolism is the expected end state of most, if not all, risk factors preceding the onset of major NDDs. This review proposes that the initial oxidative stress in the brain resulting specifically from the hyperactivation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) causes a decline in glucose utilization and is the primary initiating factor of major NDDs. The existing clinical and experimental evidence points to NOX as the primary initiating mechanism shared within the major NDDs. During early oxidative stress, NOX activation is triggered in variable brain cells via multiple pathways, from beta-amyloid to alpha-synuclein, fibrin to glutamate and seizures. Therefore, the treatment strategy should have targeted the activation of NOX, wouldn’t there be a lack of clinically approved selective NOX antagonists? On the other hand, there are promising metabolism-altering approaches via dietary means able to switch energy intake from glucose to ketones, which influences both oxidative stress and glucose utilization and could ameliorate disease progression. The regimen of time-restricted eating appears to be the most feasible, nutritious, and palatable one providing the essential benefits of a ketogenic diet without adverse effects.

The Importance of Dietary Fiber for Metabolic Health.

Dietary fiber are non-digestible carbohydrates that are diverse, have varied functions, and are acquired by consuming plant-based foods. Some forms of fiber are digested by the gut microbiota and produce bioactive metabolites called short chain fatty acids-butyrate, acetate, and propionate. Dietary fiber is able to alter human physiology through multiple mechanisms that can result in health benefits. Unfortunately, nearly 19 out of 20 Americans do not consume the minimum recommended amount of fiber each day. This bears profound relevance to public health because at least six of the ten leading causes of death are potentially preventable or clinically improved through dietary means. Additionally, these same conditions share a common underlying pathophysiology-metabolic dysfunction. This can manifest as abdominal obesity, high blood pressure, insulin resistance, dyslipidemia, or collectively as metabolic syndrome. In this review, we will assess the evidence that consumption of dietary fiber undermines these forms of metabolic dysfunction, examine the mechanism of action for these physiologic effects, and consider the potential for dietary fiber to improve human health on a public health level by simply encouraging our patients to consume more plant-based foods in abundance and diversity.

Effect of Diet on Depression: A Review of Nutritional Solutions

Depression is a mental illness with several categories that have common symptoms such as chronic sorrow, lack of interest, lack of pleasure, mood swings between guilt and poor self-esteem, sleep disturbances, and a loss of appetite. Over 300 million individuals globally suffer from depression, and the socioeconomic cost of this debilitating disorder is expected to rise dramatically in the future decades.
 Behavioral health illnesses can be prevented and treated to some extent with dietary and nutritional means. Nutritional psychiatry has produced observational and effectiveness evidence regarding the role of healthy dietary patterns in the onset and treatment of depressive symptoms. Diet is associated with depressive symptoms or depression, meaning that an increase in depressive disorders coincide with a deterioration in healthy living choices, including poor quality diets.
 Healthy eating habits and adequate intake of essential nutrients via the diet can help prevent and treat depression by reducing symptoms of mental illness. In addition, because nutrition is a modifiable risk factor for depression, it is practical for the public to consider dietary changes to reduce the prevalence of depressive disorders.
 This paper reviews the potential value of diet-based actions to manage depression, and ways in which dietary changes could be made to improve mental and cognitive health. Furthermore, some practical solutions for preventing and controlling depression are proposed based on health-related effects of improving dietary habits and life style.

Phytosterols and Cardiovascular Risk Evaluated against the Background of Phytosterolemia Cases-A German Expert Panel Statement.

Phytosterols (PSs) have been proposed as dietary means to lower plasma LDL-C. However, concerns are raised that PSs may exert atherogenic effects, which would offset this benefit. Phytosterolemia was thought to mimic increased plasma PSs observed after the consumption of PS-enriched foods. This expert statement examines the possibility of specific atherogenicity of PSs based on sterol metabolism, experimental, animal, and human data. Observational studies show no evidence that plasma PS concentrations would be associated with an increased risk of atherosclerosis or cardiovascular (CV) events. Since variants of the ABCG5/8 transporter affect the absorption of cholesterol and non-cholesterol sterols, Mendelian randomization studies examining the effects of ABCG5/8 polymorphisms cannot support or refute the potential atherogenic effects of PSs due to pleiotropy. In homozygous patients with phytosterolemia, total PS concentrations are ~4000% higher than under physiological conditions. The prevalence of atherosclerosis in these individuals is variable and may mainly relate to concomitant elevated LDL-C. Consuming PS-enriched foods increases PS concentrations by ~35%. Hence, PSs, on a molar basis, would need to have 20-40 times higher atherogenicity than cholesterol to offset their cholesterol reduction benefit. Based on their LDL-C lowering and absence of adverse safety signals, PSs offer a dietary approach to cholesterol management. However, their clinical benefits have not been established in long-term CV endpoint studies.

Abstract IA046: Mechanistic targets and strategies to break the obesity-cancer link

Abstract Obesity promotes the incidence and progression of many cancers including breast cancer. Mechanisms underpinning obesity-driven breast cancer that could be harnessed to intercept this deleterious relationship are not completely understood. Here we apply multi-omics analysis of tumor and adipose to delineate candidate mediators underlying the procancer effects of obesity, and anticancer effects of weight loss, in a mouse model of obesity-driven breast cancer. We modeled bariatric surgery and nonsurgical weight loss in obese C57BL/6NCrl mice fed a high-fat diet (60 kcal% fat) using vertical sleeve gastrectomy or a sham surgery paired with (i) dietary weight loss via ad libitum low-fat diet (10 kcal% fat), (ii) 30% chronic calorie restriction, or (iii) intermittent calorie restriction. Once weight loss stabilized, mammary tumors were induced by orthotopic transplantation of E0771 cells, a model of triple negative breast cancer (TNBC). While bariatric surgery and a switch to low-fat diet were each moderately effective at reducing tumor mass, chronic and intermittent calorie restriction regimens were each highly effective in reducing tumor burden. Tumor transcriptomic analysis using gene set enrichment analysis revealed that weight loss interventions reversed obesity-associated immunosuppression. Mediation analysis identified weight loss and fat mass loss as significant mediators of the reduced tumor mass seen in all interventions. Integration of adipose transcriptomics and reduced-representation bisulfite sequencing identified NFKB1, FXR1, and BACH1 as regulators overrepresented in differentially methylated genes, and conserved with predicted regulators of transcriptional remodeling in human adipose tissue following bariatric surgery. These data indicate that weight loss through dietary and surgical means promotes antitumor immunity, in part via remodeling of tumor adjacent adipose tissue. We have identified several candidate mediators of adipose remodeling that may underpin the antitumor effects of bariatric surgery, and these mediators represent potential mechanism-based targets for future interventions. Citation Format: Michael F. Coleman. Mechanistic targets and strategies to break the obesity-cancer link [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA046.

Food Group, Macronutrient Intake, and Metabolic Status in the US-Affiliated Pacific’s Children’s Healthy Living (CHL) Program

The Children's Healthy Living study provided dietary intake information for understudied Native Hawaiian and Other Pacific Islander (NHOPI) young children. Our objective was to describe food group and macronutrient intakes of NHOPI children in the US-Affiliated Pacific region (USAP), overall and by jurisdiction, income level, and metabolic status. We evaluated 2-8-y-olds (n=3520) in a cross-sectional cluster sampled study using 2 d of dietary records completed by caregivers using provided tools, quantified by a specially developed food composition table and compared with US dietary recommendations. Overweight and obesity (OWOB) and acanthosis nigricans (AN) assessment (metabolic status) was completed by trained evaluators using standard tools. Demographic data were collected by questionnaire. Regression analysis identified differences in dietary component means by jurisdiction, World Bank income groups (WBIGs), and metabolic status, adjusted for age and sex. Few children met US recommendations for vegetable (2.4%) and milk (4.1%) food groups. US macronutrient recommendations were generally met. Food group and macronutrient intakes were significantly different by jurisdiction and WBIG. Means for food groups, except meats, and macronutrients, except protein, were higher in overweight/obese (OWOB) compared with healthy-weight children. Grain intake of 7.25 (SE: 0.08) oz was higher (P<0.05) and milk intake of 0.90 (SE: 0.05) cups was lower (P<0.05) in children with OWOB compared with those without OWOB [grains: 7.17 (SE: 0.07) oz; and milk: 0.96 (SE: 0.04) cups]. Monounsaturated fat intake of 11.68 (SE: 0.10) % energy was higher in those with OWOB, compared with healthy-weight children [11.56 (SE: 0.08) % energy, P<0.05]. Young children's diets in the USAP did not meet milk, vegetable, or fruit intake recommendations. There was variability in dietary patterns across the USAP and by WBIG. Grain intake and monounsaturated fat intake were lower and milk intake was higher in children with better metabolic status.

Dietary Capsaicin: A Spicy Way to Improve Cardio-Metabolic Health?

Today's sedentary lifestyle with too much food and too little exercise has made metabolic syndrome a pandemic. Metabolic syndrome is a major risk factor for type-2 diabetes and cardiovascular disease. New knowledge of medical and nutraceutical intervention in the early stages of metabolic syndrome is central to prevent these deadly complications. People who eat chili pepper on a regular basis seem to stay healthier and live longer than those who do not. Animal experiments suggest a therapeutic potential for dietary capsaicin, the active principle in hot chili pepper, to reduce the risk of developing metabolic syndrome. This is an attractive theory since capsaicin has been a culinary staple for thousands of years, and is generally deemed safe when consumed in hedonically acceptable doses. The broad expression of the capsaicin receptor TRPV1 in metabolically active tissues lends experimental support to this theory. This review critically evaluates the available experimental and clinical evidence for and against dietary capsaicin being an effective dietary means to improve cardio-metabolic health. It comes to the conclusion that although a chili pepper-rich diet is associated with a reduced risk of dying due to cardiovascular disease, dietary capsaicin has no clear effect on blood glucose or lipid profiles. Therefore, the reduced mortality risk may reflect the beneficial action of digested capsaicin on gut microbiota.