Perspective: Observational Studies Involving Low-Soy Intake Populations Have Limited Ability for Providing Insight into the Health Effects of Soybean Isoflavones.

Isoflavones are naturally occurring plant compounds found in uniquely high amounts in soybeans and foods made from this legume. These soybean constituents have been proposed to exert several health benefits and as such they have been the subject of an enormous amount of research. This research includes randomized controlled trials (RCTs) and epidemiologic investigations. Although statistically significant associations between isoflavone intake and a wide range of health outcomes have been identified in cohorts involving low-isoflavone intake populations, we suggest that these associations are unlikely to have a causal basis because exposure is too low for isoflavones to exert physiologic effects. In cohorts involving predominantly non-Asian, non-vegetarian populations, the highest isoflavone intake category is typically ≤3 mg/d, an amount of isoflavones provided by ∼30 mL (2 tablespoons) of soymilk made from whole soybeans. In comparison, mean isoflavone intake in the upper intake categories in observational studies involving high-isoflavone intake populations is typically ≥50 mg/d. In RCTs, intervention doses of isoflavones typically range between 40 and 100 mg/d. Health professionals advising patients and clients about soy food and isoflavone intake need to be aware of the limitations of epidemiologic research involving low-isoflavone intake populations. Intake recommendations are best based on the results of RCTs using clinically relevant doses of isoflavones and epidemiologic studies involving populations for whom soy foods are a habitual part of the diet.

Options for substantiating protein content claims for conventional foods.

In Canada and the United States, front-of-package protein content claims require data to support the quality of the protein. In general, protein quality reflects the product of the amino acid composition of the food protein relative to human amino acid requirements and a measure of digestibility. The currently accepted method in both jurisdictions is the protein digestibility-corrected amino acid score (PDCAAS) that requires the measurement of true fecal protein (nitrogen) digestibility. The latter must be measured in vivo using a rat model. This requirement for animal testing is inconsistent with international efforts to reduce the usage of animals in testing for regulatory purposes. The current commentary positions four options to remove the need to use animal testing for determining protein quality, when considering protein content claim substantiation. These options include (i) a focus on protein quantity alone; (ii) the use of the amino acid score alone, with no correction for digestibility; (iii) the use of a fixed digestibility coefficient to estimate protein quality; and (iv) the use of in vitro methods to measure protein and/or amino acid digestibility. The relative merits and deficiencies of the options are positioned with the goal of encouraging dialogue within the regulatory agencies to move towards alternative approaches for substantiating protein content claims on foods, including those derived from plant-based sources.

Perspective: A Research Roadmap about Ultra-Processed Foods and Human Health for the United States Food System: Proceedings from an Interdisciplinary, Multi-Stakeholder Workshop.

Our objective was to convene interdisciplinary experts from government, academia, and industry to develop a Research Roadmap to identify research priorities about processed food intake and risk for obesity and cardiometabolic diseases (CMD) among United States populations. We convened attendees at various career stages with diverse viewpoints in the field. We held a "Food Processing Primer" to build foundational knowledge of how and why foods are processed, followed by presentations about how processed foods may affect energy intake, obesity, and CMD risk. Breakout groups discussed potential mechanistic and confounding explanations for associations between processed foods and obesity and CMD risk. Facilitators created research questions (RQs) based on key themes from discussions. Different breakout groups convened to discuss what is known and unknown for each RQ and to develop sub-RQs to address gaps. Workshop attendees focused on ultra-processed foods (UPFs; Nova Group 4) because the preponderance of evidence is based on this classification system. Yet, heterogeneity and subjectivity in UPF classification was a challenge for RQ development. The 6 RQs were: 1) What objective methods or measures could further categorize UPFs, considering food processing, formulation, and the interaction of the two? 2) How can exposure assessment of UPF intake be improved? 3) Does UPF intake influence risk for obesity or CMDs, independent of diet quality? 4) What, if any, attributes of UPFs influence ingestive behavior and contribute to excess energy intake? 5) What, if any, attributes of UPFs contribute to clinically meaningful metabolic responses? 6) What, if any, external environmental factors lead people to consume high amounts of UPFs? Uncertainty and complexity around UPF intake warrant further complementary and interdisciplinary causal, mechanistic, and methodological research related to obesity and CMD risk to understand the utility of applying classification by degree of processing to foods in the United States.

Dietary Guidelines Meet NOVA: Developing a Menu for A Healthy Dietary Pattern Using Ultra-Processed Foods.

BACKGROUND: A proposed topic for the 2025 Dietary Guidelines for Americans (DGA) Scientific Advisory Committee to address is the relationship between dietary patterns with ultra-processed foods (UPF) and body composition and weight status. Implementing the NOVA system, the most commonly applied framework for determining whether a food is "ultra-processed," in dietary guidance could omit several nutrient-dense foods from recommended healthy diets in the DGA. OBJECTIVE: The purpose of this proof-of-concept study was to determine the feasibility of building a menu that aligns with recommendations for a healthy dietary pattern from the 2020 DGA and includes ≥80% kcal from UPF as defined by NOVA. DESIGN: To accomplish this objective, we first developed a list of foods that fit NOVA criteria for UPF, fit within dietary patterns in the 2020 DGA, and are commonly consumed by Americans. We then used these foods to develop a 7-d, 2000 kcal menu modeled on MyPyramid sample menus and assessed this menu for nutrient content as well as for diet quality using the Healthy Eating Index-2015 (HEI-2015). RESULTS: In the ultra-processed DGA menu that was created, 91% of kcal were from UPF, or NOVA category 4. The HEI-2015 score was 86 out of a possible 100 points. This sample menu did not achieve a perfect score due primarily to excess sodium and an insufficient amount of whole grains. This menu provided adequate amounts of all macro- and micronutrients except vitamin D, vitamin E, and choline. CONCLUSIONS: Healthy dietary patterns can include most of their energy from UPF, still receive a high diet quality score, and contain adequate amounts of most macro- and micronutrients.

Perspective: Plant-Based Meat Alternatives Can Help Facilitate and Maintain a Lower Animal to Plant Protein Intake Ratio.

The health and environmental advantages of plant-predominant diets will likely lead to increasing numbers of consumers reducing their reliance on animal products. Consequently, health organizations and professionals will need to provide guidance on how best to make this change. In many developed countries, nearly twice as much protein is derived from animal versus plant sources. Potential benefits could result from consuming a higher share of plant protein. Advice to consume equal amounts from each source is more likely to be embraced than advice to eschew all or most animal products. However, much of the plant protein currently consumed comes from refined grains, which is unlikely to provide the benefits associated with plant-predominant diets. In contrast, legumes provide ample amounts of protein as well other components such as fiber, resistant starch, and polyphenolics, which are collectively thought to exert health benefits. But despite their many accolades and endorsement by the nutrition community, legumes make a negligible contribution to global protein intake, especially in developed countries. Furthermore, evidence suggests the consumption of cooked legumes will not substantially increase over the next several decades. We argue here that plant-based meat alternatives (PBMAs) made from legumes are a viable alternative, or a complement, to consuming legumes in the traditional manner. These products may be accepted by meat eaters because they can emulate the orosensory properties and functionality of the foods they are intended to replace. PBMAs can be both transition foods and maintenance foods in that they can facilitate the transition to a plant-predominant diet and make it easier to maintain. PBMAs also have a distinct advantage of being able to be fortified with shortfall nutrients in plant-predominant diets. Whether existing PBMAs provide similar health benefits as whole legumes, or can be formulated to do so, remains to be established.

Rare variants and HLA haplotypes associated in patients with neuromyelitis optica spectrum disorders.

Neuromyelitis optica spectrum disorders (NMOSD) are rare, debilitating autoimmune diseases of the central nervous system. Many NMOSD patients have antibodies to Aquaporin-4 (AQP4). Prior studies show associations of NMOSD with individual Human Leukocyte Antigen (HLA) alleles and with mutations in the complement pathway and potassium channels. HLA allele associations with NMOSD are inconsistent between populations, suggesting complex relationships between the identified alleles and risk of disease. We used a retrospective case-control approach to identify contributing genetic variants in patients who met the diagnostic criteria for NMOSD and their unaffected family members. Potentially deleterious variants identified in NMOSD patients were compared to members of their families who do not have the disease and to existing databases of human genetic variation. HLA sequences from patients from Belgrade, Serbia, were compared to the frequency of HLA haplotypes in the general population in Belgrade. We analyzed exome sequencing on 40 NMOSD patients and identified rare inherited variants in the complement pathway and potassium channel genes. Haplotype analysis further detected two haplotypes, HLA-A*01, B*08, DRB1*03 and HLA-A*01, B*08, C*07, DRB1*03, DQB1*02, which were more prevalent in NMOSD patients than in unaffected individuals. In silico modeling indicates that HLA molecules within these haplotypes are predicted to bind AQP4 at several sites, potentially contributing to the development of autoimmunity. Our results point to possible autoimmune and neurodegenerative mechanisms that cause NMOSD, and can be used to investigate potential NMOSD drug targets.

Imaging features of anorectal proctitis in monkeypox infection.

The monkeypox outbreak of 2022 saw the first community-sustained transmission of the monkeypox virus outside of Africa, and rapidly developed into multi-country spread. A common presenting sign of monkeypox infection during this outbreak has been rectal pain due to proctitis. Proctitis with large hypoattenuated anorectal ulcers on CT scan should invoke consideration for monkeypox infection in young homosexual or bisexual men with associated skin eruptions.

The health effects of soy: A reference guide for health professionals.

Soy is a hotly debated and widely discussed topic in the field of nutrition. However, health practitioners may be ill-equipped to counsel clients and patients about the use of soyfoods because of the enormous, and often contradictory, amount of research that has been published over the past 30 years. As interest in plant-based diets increases, there will be increased pressure for practitioners to gain a working knowledge of this area. The purpose of this review is to provide concise literature summaries (400-500 words) along with a short perspective on the current state of knowledge of a wide range of topics related to soy, from the cholesterol-lowering effects of soy protein to the impact of isoflavones on breast cancer risk. In addition to the literature summaries, general background information on soyfoods, soy protein, and isoflavones is provided. This analysis can serve as a tool for health professionals to be used when discussing soyfoods with their clients and patients.

Perspective: Soybeans Can Help Address the Caloric and Protein Needs of a Growing Global Population.

Feeding a growing global population with projected rising socioeconomic status will require additional sources of calories and especially protein. These sources need to align with the Sustainable Development Goals established by the Food and Agriculture Organization of the United Nations. The soybean is uniquely positioned to meet this challenge based on the following criteria: (1) Global soybean production exceeds by ~4 times the production of all pulses combined (2) Soybeans are higher in protein than other legumes and soy protein quality is similar to animal protein quality (3) Soybeans are an excellent source of healthy fat, including both essential fatty acids (4) Soybeans, like other legumes, symbiotically fix atmospheric nitrogen thereby reducing the need for fertilizer inputs (5) Greenhouse gas emissions per unit protein are lower than for nearly all other foods (6) Soybeans, like other legumes, are also recognized as an affordable food that can be incorporated into diverse diets regardless of economic standing and (7) The range of foods produced from soybeans constitutes an important position in historic and contemporary cuisines, cultures and emerging consumer trends for plant-based protein. Although most soybeans are currently used for animal feed, soybean use is dictated by consumer demand. Therefore, soybeans are well positioned to meet future global needs for energy and protein. Armed with this knowledge, health professionals can feel justified in encouraging greater consumption of soyfoods for both personal and planetary reasons.

Perspective: Soy-based Meat and Dairy Alternatives, Despite Classification as Ultra-processed Foods, Deliver High-quality Nutrition on Par with Unprocessed or Minimally Processed Animal-based Counterparts.

In many non-Asian countries, soy is consumed via soy-based meat and dairy alternatives, in addition to the traditional Asian soyfoods, such as tofu and miso. Meat alternatives are typically made using concentrated sources of soy protein, such as soy protein isolate (SPI) and soy protein concentrate (SPC). Therefore, these products are classified as ultra-processed foods (UPFs; group 4) according to NOVA, an increasingly widely used food-classification system that classifies all foods into 1 of 4 groups according to the processing they undergo. Furthermore, most soymilks, even those made from whole soybeans, are also classified as UPFs because of the addition of sugars and emulsifiers. Increasingly, recommendations are being made to restrict the consumption of UPFs because their intake is associated with a variety of adverse health outcomes. Critics of UPFs argue these foods are unhealthful for a wide assortment of reasons. Explanations for the proposed adverse effects of UPFs include their high energy density, high glycemic index (GI), hyper-palatability, and low satiety potential. Claims have also been made that UPFs are not sustainably produced. However, this perspective argues that none of the criticisms of UPFs apply to soy-based meat and dairy alternatives when compared with their animal-based counterparts, beef and cow milk, which are classified as unprocessed or minimally processed foods (group 1). Classifying soy-based meat and dairy alternatives as UPFs may hinder their public acceptance, which could detrimentally affect personal and planetary health. In conclusion, the NOVA classification system is simplistic and does not adequately evaluate the nutritional attributes of meat and dairy alternatives based on soy.

Neither soyfoods nor isoflavones warrant classification as endocrine disruptors: a technical review of the observational and clinical data.

Soybeans are a rich source of isoflavones, which are classified as phytoestrogens. Despite numerous proposed benefits, isoflavones are often classified as endocrine disruptors, based primarily on animal studies. However, there are ample human data regarding the health effects of isoflavones. We conducted a technical review, systematically searching Medline, EMBASE, and the Cochrane Library (from inception through January 2021). We included clinical studies, observational studies, and systematic reviews and meta-analyses (SRMA) that examined the relationship between soy and/or isoflavone intake and endocrine-related endpoints. 417 reports (229 observational studies, 157 clinical studies and 32 SRMAs) met our eligibility criteria. The available evidence indicates that isoflavone intake does not adversely affect thyroid function. Adverse effects are also not seen on breast or endometrial tissue or estrogen levels in women, or testosterone or estrogen levels, or sperm or semen parameters in men. Although menstrual cycle length may be slightly increased, ovulation is not prevented. Limited insight could be gained about possible impacts of in utero isoflavone exposure, but the existing data are reassuring. Adverse effects of isoflavone intake were not identified in children, but limited research has been conducted. After extensive review, the evidence does not support classifying isoflavones as endocrine disruptors.

Soybean oil lowers circulating cholesterol levels and coronary heart disease risk, and has no effect on markers of inflammation and oxidation.

To reduce risk of coronary heart disease, replacement of saturated fats (SFAs) with polyunsaturated fats (PUFA) is recommended. Strong and concordant evidence supports this recommendation, but controversy remains. Some observational studies have reported no association between SFAs and coronary heart disease, likely because of failure to account for the macronutrient replacing SFAs, which determines the direction and strength of the observed associations. Controversy also persists about whether ω-6 (nω-6) PUFA or a high dietary ratio of nω-6 to ω-3 (nω-3) fatty acids leads to proinflammatory and pro-oxidative states. These issues are relevant to soybean oil, which is the leading edible oil consumed globally and in the United States. Soybean oil accounts for over 40% of the US intake of both essential fatty acids. We reviewed clinical and epidemiologic literature to determine the effects of soybean oil on cholesterol levels, inflammation, and oxidation. Clinical evidence indicates that soybean oil does not affect inflammatory biomarkers, nor does it increase oxidative stress. On the other hand, it has been demonstrated that when dietary SFAs are replaced with soybean oil, blood cholesterol levels are lowered. Regarding the nω-6:nω-3 dietary ratio, health agencies have consistently rejected the importance of this ratio, instead emphasizing the importance of consuming sufficient amounts of each type of fat. Thus, several lines of evidence indicate that soybean oil can positively contribute to overall health and reduction of risk of coronary heart disease.

Impact of the COVID-19 pandemic on radiology department emergency ultrasound utilization.

PURPOSE: To analyze the change in utilization of healthcare resources through a review of ultrasound examinations performed in the emergency department of an urban healthcare system in NYC during the time of peak COVID-19 outbreak. METHODS: This is a retrospective review analyzing ED ultrasound exams performed by the radiology department of an urban healthcare system during the 8-week time period of the peak COVID-19 outbreak in NYC, compared to a time-matched period one year prior. Data regarding the examination type and indication were obtained in addition to patient demographics and indicators of outcomes including admission, length of stay, and mortality. RESULTS: There was a 58% decrease in ED ultrasounds performed by the radiology department during the COVID-19 time period. Exams performed during the pandemic compared to the pre-pandemic period were more likely to be performed on men (28.3 vs 18.0%, p < 0.01), older patients (36 vs. 35 years, p = 0.02), and patients subsequently admitted (17.8 vs. 13.4%, p = 0.03). There was also a difference in the distribution of exam type (p = 0.01). There was no difference in death, rate of surgery/intervention performed, or distribution of clinical indication. When correcting for gender, there was only an increase in studies leading to hospital admission in the female-only group (14.9 vs. 10.7%, p = 0.05). CONCLUSION: COVID-19 had a drastic impact on the utilization of emergency department ultrasounds performed by the radiology department, with a decrease in total exams performed and changes in patient demographics, including a higher proportion of male patients and increases in some markers of disease severity, including rate of hospital admission.

Neither soy nor isoflavone intake affects male reproductive hormones: An expanded and updated meta-analysis of clinical studies.

Concerns that the phytoestrogens (isoflavones) in soy may feminize men continue to be raised. Several studies and case-reports describing feminizing effects including lowering testosterone levels and raising estrogen levels in men have been published. For this reason, the clinical data were meta-analyzed to determine whether soy or isoflavone intake affects total testosterone (TT), free testosterone (FT), estradiol (E2), estrone (E1), and sex hormone binding globulin (SHBG). PubMed and CAB Abstracts databases were searched between 2010 and April 2020, with use of controlled vocabulary specific to the databases. Peer-reviewed studies published in English were selected if (1) adult men consumed soyfoods, soy protein, or isoflavone extracts (from soy or red clover) and [2] circulating TT, FT, SHBG, E2 or E1 was assessed. Data were extracted by two independent reviewers. With one exception, studies included in a 2010 meta-analysis were included in the current analysis. A total of 41 studies were included in the analyses. TT and FT levels were measured in 1753 and 752 men, respectively; E2 and E1 levels were measured in 1000 and 239 men, respectively and SHBG was measured in 967 men. Regardless of the statistical model, no significant effects of soy protein or isoflavone intake on any of the outcomes measured were found. Sub-analysis of the data according to isoflavone dose and study duration also showed no effect. This updated and expanded meta-analysis indicates that regardless of dose and study duration, neither soy protein nor isoflavone exposure affects TT, FT, E2 or E1 levels in men.

Cytotoxic lesion of the splenium of the corpus callosum in a patient with EVALI.

Since first recognized in July 2019, numerous cases of a lung illness associated with electronic-cigarette use or vaping particularly tetrahydrocannabinol in adolescents and adults have been reported. As of January 2020, the Center for Disease Control has reported over 2500 cases of electronic-cigarette or vaping product use-associated lung injury (EVALI), including 60 deaths. Affected patients most commonly present with respiratory or gastrointestinal complaints although neurological symptoms including headache, confusion and lethargy have been reported. We present a new as yet unpublished finding in the brain of a previously healthy teenage boy with EVALI. Brain imaging may be warranted in this patient population.

Vaping associated lung injury: A potentially life-threatening epidemic in US youth.

BACKGROUND: The Center for Disease Control (CDC) has identified a national outbreak in the United States of over 2600 cases of e-cigarette or vaping product use-associated lung injury (EVALI), including 60 deaths as of January 2020. We describe our experience in six adolescents. MATERIAL AND METHODS: We identified all pediatric patients diagnosed with EVALI by CDC guidelines over a 6-month period at our health system. Clinical presentation, hospital course, and imaging were reviewed. RESULTS: Six patients were identified (three males, three females; median age 18.5 years). Presenting symptoms varied, including constitutional, gastrointestinal, neurologic, and respiratory complaints with pulmonary symptomatology becoming the dominant feature of the illness. Three patients required intensive care unit-level care, one of whom expired 36 days after presentation. Three had bronchoalveolar lavage, two with evidence of lipid-laden macrophages. Four had pulmonary function testing with various results. Admission chest radiographs in all revealed bibasilar interstitial infiltrate which rapidly progressed. Five patients had computed tomography chest imaging demonstrating: confluent pulmonary infiltrates with subpleural sparing (n = 2), generalized ground-glass opacities (n = 1), patchy ground-glass opacities (n = 1) and a reticulonodular pattern (n = 1). Brain magnetic resonance imaging (MRI) obtained in two patients was normal in one and showed a focal signal abnormality in the corpus callosum in one. CONCLUSION: We describe the clinical course and radiologic findings of EVALI in our adolescent patients and present a new finding in the brain not yet described in the literature. Given the diversity of presenting symptoms, a high level of suspicion for EVALI is necessary for patients reporting vaping product use regardless of the presence of pulmonary complaints. Brain MRI should be strongly considered in patients with neurologic symptoms.

A Meta-Analysis of 46 Studies Identified by the FDA Demonstrates that Soy Protein Decreases Circulating LDL and Total Cholesterol Concentrations in Adults.

BACKGROUND: Certain plant foods (nuts and soy protein) and food components (viscous fibers and plant sterols) have been permitted by the FDA to carry a heart health claim based on their cholesterol-lowering ability. The FDA is currently considering revoking the heart health claim for soy protein due to a perceived lack of consistent LDL cholesterol reduction in randomized controlled trials. OBJECTIVE: We performed a meta-analysis of the 46 controlled trials on which the FDA will base its decision to revoke the heart health claim for soy protein. METHODS: We included the 46 trials on adult men and women, with baseline circulating LDL cholesterol concentrations ranging from 110 to 201 mg/dL, as identified by the FDA, that studied the effects of soy protein on LDL cholesterol and total cholesterol (TC) compared with non-soy protein. Two independent reviewers extracted relevant data. Data were pooled by the generic inverse variance method with a random effects model and expressed as mean differences with 95% CI. Heterogeneity was assessed and quantified. RESULTS: Of the 46 trials identified by the FDA, 43 provided data for meta-analyses. Of these, 41 provided data for LDL cholesterol, and all 43 provided data for TC. Soy protein at a median dose of 25 g/d during a median follow-up of 6 wk decreased LDL cholesterol by 4.76 mg/dL (95% CI: -6.71, -2.80 mg/dL, P < 0.0001; I2 = 55%, P < 0.0001) and decreased TC by 6.41 mg/dL (95% CI: -9.30, -3.52 mg/dL, P < 0.0001; I2 = 74%, P < 0.0001) compared with non-soy protein controls. There was no dose-response effect or evidence of publication bias for either outcome. Inspection of the individual trial estimates indicated most trials (∼75%) showed a reduction in LDL cholesterol (range: -0.77 to -58.60 mg/dL), although only a minority of these were individually statistically significant. CONCLUSIONS: Soy protein significantly reduced LDL cholesterol by approximately 3-4% in adults. Our data support the advice given to the general public internationally to increase plant protein intake. This trial was registered at clinicaltrials.gov as NCT03468127.

No Difference Between the Effects of Supplementing With Soy Protein Versus Animal Protein on Gains in Muscle Mass and Strength in Response to Resistance Exercise.

Much attention has been given to determining the influence of total protein intake and protein source on gains in lean body mass (LBM) and strength in response to resistance exercise training (RET). Acute studies indicate that whey protein, likely related to its higher leucine content, stimulates muscle protein synthesis to a greater extent than proteins such as soy and casein. Less clear is the extent to which the type of protein supplemented impacts strength and LBM in long-term studies (≥6 weeks). Therefore, a meta-analysis was conducted to compare the effect of supplementation with soy protein to animal protein supplementation on strength and LBM in response to RET. Nine studies involving 266 participants suitable for inclusion in the meta-analysis were identified. Five studies compared whey with soy protein, and four studies compared soy protein with other proteins (beef, milk, or dairy protein). Meta-analysis showed that supplementing RET with whey or soy protein resulted in significant increases in strength but found no difference between groups (bench press: χ2 = 0.02, p = .90; squat: χ2 = 0.22, p = .64). There was no significant effect of whey or soy alone (n = 5) on LBM change and no differences between groups (χ2 = 0.00, p = .96). Strength and LBM both increased significantly in the "other protein" and the soy groups (n = 9), but there were no between-group differences (bench: χ2 = 0.02, p = .88; squat: χ2 = 0.78, p = .38; and LBM: χ2 = 0.06, p = .80). The results of this meta-analysis indicate that soy protein supplementation produces similar gains in strength and LBM in response to RET as whey protein.