Supplement Intake Research Articles

Effects of selected dietary supplements on migraine prophylaxis: A systematic review and dose-response meta-analysis of randomized controlled trials.

The existing evidence on the effect of dietary supplements for preventing migraines has generated conflicting results. We assessed alterations in migraine clinical features corresponding to the intake of dietary supplements. Our main outcomes included the frequency (number of attacks), duration (in hours), the severity (intensity) and the monthly migraine days. Using a dose-response meta-analysis, we estimated the dose-dependent impact. The certainty of evidence was evaluated using the GRADE tool. Finally, twenty-two trials were included in the systematic review and meta-analysis. Magnesium supplementation reduced migraine attacks (mean difference (MD) = -2.51), severity (MD = -0.88), and the monthly migraine days (MD = -1.66) compared with the control group. CoQ10 decreased the frequency (MD = -1.73), severity (MD = -1.35), and duration of migraine (MD = -1.72). Riboflavin decreased attack frequency (MD = -1.34). Alpha-lipoic acid decreased attack frequency (MD = -1.24) and severity (MD = -0.38). Probiotics decreased the frequency (MD = -1.16), severity (MD = -1.07) and the monthly migraine days (MD = -3.02). Vitamin D reduced migraine frequency (MD = -1.69) and the monthly migraine days (MD = -2.41). In adults, compared with placebo, these supplements did not significantly affect other outcomes, and omega-3 supplementation did not yield a statistically significant reduction in any of these outcomes. The use of certain dietary supplements has resulted in a significant decrease in migraine prophylaxis. Further clinical trials of high quality appear to be beneficial.

Routine uptake of prenatal iron-folic acid supplementation and associated factors among pregnant women in peri-urban areas of Dodoma City, Tanzania: a cross-sectional study

BackgroundThe physiological requirements for iron and folic acid in pregnancy are a significant challenge to achieve through normal dietary intake, especially in low resource settings. The World Health Organization recommends daily oral iron and folic acid supplementation (IFAS) to prevent maternal anaemia and related adverse effects in community settings where the prevalence of anaemia during pregnancy is > 40%. The objective of this study was to assess the routine uptake of prenatal iron-folic acid supplementation and associated factors among pregnant women at peri-urban areas of Dodoma City, Tanzania.MethodsA cross-sectional study was conducted in peri-urban areas. Data was collected through face-to-face interviews and review of records from maternal clinic card (RCH 4 card). Routine uptake of iron-folic acid supplementation was defined as pregnant woman who reported taking iron-folic acid supplements at least once within the past seven days prior to data collection. Frequency and percentage were used to report respondents’ characteristics and uptake of prenatal iron-folic acid supplementation. Chi-square test and logistic regression were conducted to determine the relationship and association of routine uptake of iron-folic acid supplementation with respondents’ characteristics.ResultsThe total respondents were 452. Overall routine uptake of iron-folic acid supplementation was 35.6% (161). The majority of the respondents (66.5%) initiated iron-folic acid supplementation during the second trimester of pregnancy. Most of the respondents (86.3%) obtained IFA supplements at the health centers where they were receiving antenatal care. The prevalence of routine uptake of iron-folic acid supplementation was significantly higher among women in the third trimester of pregnancy (54.9%), those with more than a five-year interval since last pregnancy (40.6%), those with at least four antenatal care (ANC) visits (73.7%) and women who had undergone haemoglobin testing in the current pregnancy (63.0%). Factors associated with routine uptake of iron-folic acid supplementation were; frequency of ANC visits (AOR = 1.69) and haemoglobin testing (AOR = 3.02).ConclusionApproximately one third of the pregnant women took iron-folic acid supplementation at least once a week. The current frequency for intake of iron-folic acid supplementation can be described as intermittent. This practise is unacceptable for prevention of maternal anaemia and associated adverse pregnant outcomes. Frequency of ANC visits and haemoglobin testing during pregnancy were found to be associated with routine uptake of iron-folic acid supplements. Stakeholders are urged to consider novel systems for provision of prenatal IFAS in community settings with limited access to health-care professionals to ensure a timely and continuous supply of supplements.

Pilot Study on the Effect of Patient Condition and Clinical Parameters on Hypoxia-Induced Factor Expression: HIF1A, EPAS1 and HIF3A in Human Colostrum Cells

Hypoxia-inducible factor 1 (HIF-1) may play a role in mammary gland development, milk production and secretion in mammals. Due to the limited number of scientific reports on the expression of HIF genes in colostrum cells, it was decided to examine the expression of HIF1A, HIF3A and EPAS1 in the these cells, collected from 35 patients who voluntarily agreed to provide their biological material for research, were informed about the purpose of the study and signed a consent to participate in it. The expression of HIF genes was assessed using qPCR. Additionally, the influence of clinical parameters (method of delivery, occurrence of stillbirths in previous pregnancies, BMI level before pregnancy and at the moment of delivery, presence of hypertension during pregnancy, presence of Escherichia coli in vaginal culture, iron supplement and heparin intake during pregnancy) on the gene expression was assessed, revealing statistically significant correlations. The expression of HIF1A was 3.5-fold higher in the case of patients with the presence of E. coli in vaginal culture (p = 0.041) and 2.5 times higher (p = 0.031) in samples from women who used heparin during pregnancy. Approximately 1.7-fold higher expression of the EPAS1 was observed in women who did not supplement iron during pregnancy (p = 0.046). To our knowledge, these are the first studies showing the relationship between HIF expression in cells from breast milk and the method of delivery and health condition of women giving birth. The assessment of HIF expression requires deeper examination in a larger study group, and the results of further studies will allow to determine whether HIF can become biomarkers in pregnancy pathology states.

The Relationships among the Urinary Iodine Concentration, Selenium Intake, and Thyroid Antibodies in Adults, Including the Interaction between Iodine and Selenium: National Health and Nutrition Examination Survey 2007-2012.

The objective of this study was to examine the urinary iodine concentration (UIC)-thyroid autoimmunity (TAI) association and UIC-selenium intake interaction in U.S. adults. We analyzed 2007-2012 National Health and Nutrition Examination Survey (NHANES) data on ≥20-year-old adults (n = 6612). Their food and supplemental selenium intake was measured. The associations of the UIC and selenium intake with thyroid peroxidase antibody (TPOAb) positivity, thyroglobulin antibody (TgAb) positivity, and TAI were assessed via weighted multivariable logistic regression. Interaction and subgroup analyses were conducted. Nonlinear relationships were explored and visualized via restricted cubic splines (RCSs). Compared with a UIC 100~200 μg/L, a UIC 500~800 μg/L was associated with a 57% increased TPOAb positivity risk (OR = 1.57 [CI = 1.07-2.30]; p = 0.022), a one-fold greater TgAb positivity risk (OR = 2.00 [CI = 1.10-3.65]; p = 0.025), and a 62% increased TAI risk (OR = 1.62 [CI = 1.07-2.45]; p = 0.024). Nonlinear relationships between the UIC and thyroid antibody positivity were observed. According to the univariate models, each 1 μg increase in selenium intake was associated with a 0.049 IU/mL decrease in the TPOAb levels (β [95% CI] = -0.049 [-0.092--0.005]; p = 0.028). In the low-selenium group, a UIC of 200~300 μg/L was a risk factor for TPOAb positivity (p = 0.046). At a moderate level of selenium intake, a UIC of 300~800 μg/L significantly increased the TPOAb positivity risk (all p < 0.05). At a high level of selenium intake, the UIC and TPOAb positivity risks were not significantly associated (all p > 0.05). A UIC of 500~800 μg/L is an independent TAI risk factor. The selenium intake modifies the UIC-thyroid antibody positivity relationship, with the association disappearing at high selenium levels.

Association between dietary inflammatory index and all-cause mortality in US adults with dermatitis: a population-based cohort study.

While dermatitis management is primarily symptomatic, the role of diet in symptom exacerbation and improvement is increasingly recognized. The dietary inflammatory index (DII), a quantitative assessment tool for dietary inflammatory potential, has been associated with various chronic diseases but remains understudied in dermatitis. This cohort study investigated the association between DII scores and all-cause mortality among patients with dermatitis. The study included 1,074 patients with dermatitis and complete dietary intake records from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. The DII scores were calculated using two 24-h dietary recalls and dietary supplement intakes and the consumption of 28 foods with known pro- or anti-inflammatory properties. All-cause mortality information was from the National Death Index, censored on December 31, 2019. Multivariable Cox hazards regression models, restricted cubic spline (RCS) models, and subgroup analyses were employed to evaluate the association of DII with all-cause mortality, adjusting for potential confounders. The 1,074 patients were divided into DII tertiles (T1: n = 358, median age 40 years, DII -3.91, 0.06; T2: n = 296, median age 40 years, DII 0.06, 1.88; T3: n = 237, median age 39 years, DII 1.88, 4.39). The study revealed a positive correlation between higher DII scores and increased all-cause mortality risk among patients with dermatitis (fully-adjusted model, HR = 1.13, 95% CI 1.02, 1.27, p = 0.026). This association was more pronounced in adults over 45 years, with the highest DII tertile indicating a 2.42-fold increased mortality risk (95% CI 1.15, 5.07, p = 0.019) compared with the lowest tertile. The RCS model confirmed a linear dose-response trend (p for non-linear = 0.183), validating the relationship. Elevated DII scores are associated with an increased risk of all-cause mortality in patients with dermatitis, suggesting that the dietary inflammatory potential may impact health outcomes in this population. The findings underscore the importance of dietary interventions in dermatitis management, especially for middle-aged and older adults. Future research with larger cohorts and a longer follow-up is warranted to validate the findings.

Use of over-the-counter supplements, sleep aids, and analgesic medicines in rheumatology: results of a cross-sectional survey

Abstract Objectives Pain, fatigue, and sleep are common symptoms in patients with Rheumatic and Musculoskeletal diseases (RMDs) that may prompt the use of over-the-counter (OTC) supplements, sleep aids, and analgesics as self-management strategies. This study evaluated the prevalence of OTC supplements, sleep aids, pain relievers and the financial burden associated with their use in rheumatology. Methods A web-based survey developed with patients, was administered in rheumatology clinics in an English hospital. Participants shared demographic information and detailed their use of OTC supplements, sleep aids, and pain relief in the past week. The data was analysed using descriptive statistics and logistic regression models to identify influencing factors. Results In total 876 people consented to participate in the survey. Over half of patients (54.5%) reported daily supplement intake, typically spending £10/month (IQR 5-20), ranging up to £200 per month. The most commonly administered supplements were vitamin D, multivitamins, vitamin C, vitamin B/B complex, Omega 3/6 supplements, with multiple overlaps. Prescription, OTC, or non-prescription pain relief was reported by 82% of respondents, with sleep aids being used by 13%. Of the 327 patients who took NSAIDs, 165 (50.4%) also reported taking OTC supplements, while among the 131 patients using opioids (20.5%), 66 (50.3%) reported supplement use, some of which have documented interactions. Conclusion The administration of OTC supplements, pain relief, and sleep aids is common in patients with RMDs. Health care professionals should be encouraged to proactively ask about these during consultations especially from a drug safety perspective, but also to provide timely, reliable advice about such strategies that may be sought by patients.

Prevalence of Functional Cobalamin Deficiency and Relevant Mortality Risk in the General Population: An Unheeded Phenotype Distinct from Cobalamin Deficiency

Background Current guidelines prioritize monitoring and managing cobalamin (Cbl) deficiency but insufficiently address the issue of functional Cbl deficiency (decreased Cbl sensitivity). This study aims to investigate the prevalence burden of functional Cbl deficiency and to examine its prospective association with mortality risk, compared to Cbl deficiency, among United States (US) adults. Method The cohort study included 22,513 US participants aged ≥20 years from 1999 to 2014 and was followed up through December 31, 2019. Cbl sensitivity was assessed using a combination of binary classifications for Cbl and methylmalonic acid (MMA) levels, with cutoff values set at 400 pg/mL for Cbl and 250 nmol/L for MMA. Functional Cbl deficiency was defined as elevated MMA and Cbl levels. Serum Cbl levels <148 pmol/L (200 pg/mL) were classified as Cbl deficiency. Results In this study, approximately 2.1% of US adults had Cbl deficiency, while the age-adjusted prevalence of functional Cbl deficiency was 4.5%, corresponding to an estimated 10 million US adults. Over a median follow-up period of 10.7 years, there were 4636 recorded deaths. Compared to the MMAlowCbllow group (MMA ≤250 nmol/L, Cbl ≤400 pg/mL), the multivariable-adjusted hazard ratios for all-cause, cardiovascular, and cancer-related mortality in the MMAhighCblhigh group were 1.76 (95% confidence interval [CI]: 1.53–2.02, p < 0.001), 2.17 (95% CI: 1.78–2.67, p < 0.001), and 1.38 (95% CI: 0.95–2.00, p = 0.089). In contrast, the mortality risk associated with Cbl deficiency became insignificant after adjusting for similar confounders. While Cbl supplementation or dietary intake above recommended levels might alleviate Cbl deficiency, they do not appear to reduce the prevalence of functional Cbl deficiency or its associated mortality risk. Conclusion Compared with Cbl deficiency, functional Cbl deficiency is more frequent and is significantly associated with increased mortality risk in the general population.

Maternal Nutrition and Human Milk Nutrients

Abstract Purpose: To explore the influence of maternal nutrition factors, including body mass index, nutritional supplementation, and dietary intake during the breastfeeding period, on macro and micronutrient composition in human milk. Study Design and Methods: We conducted a scoping review using the PRISMA-ScR checklist, initially identifying 5,984 original studies published in the English language from PubMed, Scopus, and Web of Science that presented findings on the association of maternal nutritional factors on human milk nutrient composition. After screening the title and abstract, we selected 69 studies for full review, including 3 studies found through checking reference lists. After full review, we included 23 studies in this scoping review. Results: Most studies found maternal body mass index and supplement consumption affected human milk macro and micronutrient composition, whereas inconsistent results were found on the relationship between maternal diet and human milk nutrients. Methodologies varied substantially across studies, especially for milk sample collection methods and maternal nutrition assessments. Clinical implications: Maternal nutrition factors may affect levels of human milk nutrients, requiring maternal nutrition monitoring during breastfeeding. However, given the considerable variability in the results between studies and methodological approaches, further studies should use standardized and validated procedures to strengthen the findings on this topic.

5103 Synthroid Absorption Conundrum: A Case Deciphered

Abstract Disclosure: H. Nadeem: None. O. Alzohaili: None. Hypothyroidism is a disorder requiring lifelong Synthroid therapy. Untreated patients have high morbidity rate and suffer from weight gain, cold intolerance, fatigue and constipation. Inadequate therapeutic outcomes may result in the case of malabsorption, like GI tract conditions, medication interactions and dietary ingredients. Here, we describe the case of a 50-year-old woman who despite compliance to therapy, had refractory hypothyroidism. Complexity of unexplained Synthroid malabsorption is highlighted, emphasizing the importance of managing and optimizing thyroid hormone replacement therapy. A 50-year-old woman with a history of papillary carcinoma s/p thyroidectomy and radioactive iodine therapy came in with fatigue, weight gain and constipation. Despite taking Synthroid 150 mcg, thyroid function tests (TFTs) remained high with TSH 150 uIU/mL and fT4 0.25 ng/dL. Her dose was gradually increased until it reached 1800 mcg yet repeat TFTs showed refractory hypothyroidism with TSH 179 uIU/mL, fT4 0.8 ng/dL. Compliance was addressed to which she demonstrated strict adherence, while avoiding concurrent intake of food, supplements or medications interfering with the absorption. Autoimmune conditions were ruled out and no dietary patterns affecting absorption were identified. A thyroid absorption test was then performed, during which 2100 mcg of Synthroid were given orally in the AM, and thyroid hormones were measured for 8 hours. She was found to have a TSH in 200s uIU/mL and fT4 &amp;lt;0.10 ng/dL, deeming her to have refractory hypothyroidism. She was seen by GI and had an EGD/ colonoscopy, revealing no abnormalities. In a follow up visit, she was still complaining of the same symptoms, periorbital edema, and mild confusion. Her TSH was still elevated at 225 uIU/mL. She was then started on IV 500 mcg of weekly Synthroid infusions and after several weeks, she reported symptoms improvement. Subsequent TFTs showed a progress in TSH, now 26.6 uIU/mL, with fT4 1 ng/dL, indicating successful management of Synthroid malabsorption. During this process, she had a nutritional assessment and was consistently having hyperlipidemia with LDL 243 mg/dL. She was compliant with Praluent and max dose of atorvastatin 80 mg, but LDL only decreased to 134 mg/dL after adjusting her thyroid hormone levels. With nonadherence being the top cause of medication non responsiveness, ruling out causes of malabsorption is vital. In this case, compliance, nutritional assessment, medication interactions, GI abnormalities, autoimmune conditions were all addressed and no interfering factors were identified. IV treatment with unexplained thyroid hormone malabsorption was the effective treatment, ultimately improving outcomes. With the hope to transition her to oral medication, the possibility of it happening is still not clear. More research is necessary to discover the underlying causes in such an exceptional case. Presentation: 6/2/2024

Exposure to bisphenols, parabens, and benzophenones in colostrum breast milk of Panamanian women: A pilot study from the PA-MAMI cohort

BackgroundBreast milk is the optimal source of nutrition for infants but can also expose them to endocrine-disrupting chemicals (EDCs), among other environmental contaminants. AimTo determine concentrations of non-persistent phenolic EDCs (three bisphenols, four parabens [PBs], and six benzophenones [BPs]), in colostrum samples from Panamanian mothers and to examine associated reproductive, sociodemographic, and life-style factors. MethodsDispersive liquid–liquid microextraction was used to measure concentrations of bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS), methyl- (MeP), ethyl- (EtP), propyl- (n-PrP), and butyl-paraben (n-BuP), and benzophenones BP-1, BP-2, BP-3, BP-6, BP-8, and 4-hydroxy-BP in colostrum milk samples from 36 mothers. An ad hoc questionnaire was used to collect data on potential influentially variables, and multiple linear and logistic regression analyses were conducted. ResultsTwo or more tested EDCs were detected in 36 colostrum samples (100 %), at least four in 14 samples (38.9 %), and at least six in 4 samples (11.1 %). The most frequently detected compounds were BPA (91.7 %), BP-8 (63.9 %), MeP (47.2 %), and BPF (41.7 %). The median concentration was 3.45 ng/mL for BP-8 and 1.37 ng/mL for BPA. No concentrations of n-PrP, BP-1, BP-6, or 4-hydroxy-BP were detected. Associations were observed between phenolic EDC concentrations and maternal place of residence, consumption frequency of poultry, fish, fresh cheese, fruit, yogurt and chocolate, intake of nutritional supplements, and application of some personal care products. ConclusionsBisphenols, parabens, and benzophenones were widely present in colostrum milk samples from Panamanian women. Preventive measures are needed to maximize the benefits of breastfeeding.

7070 Nephrolithiasis and Hypercalciuria in Adults with Osteogenesis Imperfecta

Abstract Disclosure: V.R. Simões: None. M. Daly: None. M.G. Rocha-Braz: None. R.M. Martin: None. B. Ferraz-de-Souza: None. Osteogenesis imperfecta (OI) is a heterogeneous bone fragility disorder. Extra-skeletal manifestations have been well documented in children with OI, including renal complications, but studies in adults lack. Here we investigate the prevalence of nephrolithiasis and hypercalciuria in adults with OI.After informed consent, adult patients with OI attending a tertiary clinic were included in this prospective study. Disease severity score, mobility score, BMD, and molecular diagnosis, if available, were registered. Evaluation of nephrolithiasis comprised history, dietary record, and medication and supplement use. Imaging was performed in all patients with renal US and/or CT, and laboratory investigations encompassed serum (Ca, P, ALP, 25OHD, PTH, CTX, P1NP) and 24-h urine (Ca, P, citrate, oxalate, sodium, uric acid) analyses. IBM SPSS v20 was used for statistical analysis.In total, 94 adults (57 F, 37 M) with OI were evaluated, with ages ranging from 21-76 yr (50% between 20-29). Molecular diagnosis was available for 61 subjects, 79% of whom had collagen defects. Most subjects had moderate to severe OI (70%) and 48% required walking support/aid or did not walk. Excessive total (diet + supplement) daily calcium intake was identified in only 6%. Renal CT and US were available for 50 subjects (53%), CT only for 11 (12%) and US only for 33 (35%). Nephrolithiasis was identified in 26 subjects (28%). Of those, 13 (14%) had symptoms. A trend towards a higher occurrence of nephrolithiasis in subjects with moderate/severe OI was identified (p=0.059), and, reassuringly, no association with calcium intake or use of supplements was seen. ROC curve analysis revealed that 24-h U Ca &amp;gt;144.25 mg and 24-h U citrate &amp;lt;235 mg were significantly associated with nephrolithiasis (p=0.024 &amp; p=0.048). Logistic regression identified a 5.6x increased likelihood of nephrolithiasis for 24-h U oxalate &amp;gt;19 mg (p=0.047). Nephrolithiasis was identified in 28% female and 27% male subjects. Because nephrolithiasis is usually more common in males, analyses were repeated according to sex. In female subjects, nephrolithiasis was significantly associated with OI severity (p=0.01) and with higher mean OI severity scores (p=0.001). Strikingly, hypercalciuria (defined as 24-h U Ca &amp;gt;200 mg) was identified in 36% of the cohort. Significant but weak positive correlations between 24-h U Ca and mobility score (r=0.214, p=0.041) and 24-h U Na (r=0.426, p=0.001) were found, as were negative correlations with CTX (r=-0.257, p=0.015) and P1NP (r=-0.251, p=0.018). In conclusion, high prevalence of nephrolithiasis and hypercalciuria were identified in adults with OI. While Ca supplementation did not seem to be associated with risk for nephrolithiasis in this population with mostly adequate total daily intake levels, OI severity, low U citrate and high U oxalate levels seemed to increase risk, prompting attention in the care of adults with OI. Presentation: 6/1/2024

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in &amp;lt; 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone &amp;lt; 2.6 ng/dL; Total testosterone: &amp;lt; 10ng/dL; and Free androgen index &amp;lt; 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in &amp;lt; 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone &amp;lt; 2.6 ng/dL; Total testosterone: &amp;lt; 10ng/dL; and Free androgen index &amp;lt; 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

7439 Mercury toxicity presenting as Pheochromocytoma

Abstract Disclosure: A. Ansar: None. K. McNerney: None. B.A. Marshall: None. Background: Mercury intoxication is a rare cause of hypertension in children and can mimic other endocrinopathies such as pheochromocytoma. Mercury affects catecholamine metabolism and can cause elevated catecholamine levels, thereby incorrectly suggesting a catecholamine-secreting tumor. Clinical Case: An 8-year-old girl presented to the ED with progressive night sweats, intractable migratory myalgias, hypertension and tachycardia. Patient was in her usual state of health until 2 weeks before presentation when she started to have worsening intermittent pains in her chest, arms, back, and knees. She also experienced restlessness and inability to sleep. On presentation she was hypertensive, with blood pressure of 146/116 mm Hg while calm, heart rate 125 bpm, afebrile. She was anxious, irritable, and seemed uncomfortable. Her skin was dry and rough with a scaly eczematous rash on the arms and legs. She had persistently elevated blood pressure in upper and lower extremities, unremarkable echocardiogram and electrocardiogram, and a normal result on fundoscopic examination. Her initial electrolytes, creatinine, and urinalysis were all normal and remained so on serial evaluations. Urine drug screen was negative. Thyroid function panel showed normal TSH with slightly elevated Free T4 2.28 ng/dL (0.9-1.7), but a normal Free T3 3.9 pg/mL (2.0-4.4) and Free T4 by equilibrium dialysis 1.8 ng/dL (0.8 - 2.0). CT of the chest, abdomen and pelvis was negative and did not show any lesions. Plasma renin activity was 4.6 ng/mL/hour, supine, (&amp;lt;2.0) and plasma aldosterone level &amp;lt; 4.0 ng/dL (&amp;lt; 40 supine) were normal. 24-hour urinary norepinephrine was 90 μg/24h (13-65), epinephrine 37 μg/24h (0.2-10), urine metanephrines 195 μg/24h (18-144), urine normetanephrines 305 μg/24h (29-145), all elevated. Further history taking revealed that patient was taking Ayurvedic supplements prepared by hand by medicinal personnel in India for 3 months prior to presentation. These were stopped 2 weeks prior to her presentation, when she first became symptomatic. Her blood mercury level was 11 ng/mL (n &amp;lt;9), and urinary mercury excretion 67 μg/24 hours (n&amp;lt;10), both obtained 3 weeks after stopping supplementation. She was started on oral chelation therapy with succimer 10 mg/kg/day. Her hypertension was controlled with doxazosin. One week after initiation of therapy, her symptoms improved, and she became normotensive. Her acrodynia and irritability resolved. Urine metanephrine levels will be repeated at upcoming clinic follow up. Conclusion: Mercury toxicity should be considered in the differential of pheochromocytoma to avoid extensive diagnostic testing and morbidity associated with it. Lead, mercury, and arsenic have been detected in traditionally prepared Ayurvedic supplements. A careful history of intake of supplements can be important in cases with unusual symptomatology. Presentation: 6/3/2024

Iron status, anemia, and birth outcomes among pregnant women in urban Bloemfontein, South Africa: the NuEMI study

BackgroundDespite routine iron supplementation for pregnant women in South Africa, anaemia and iron deficiency (ID) in pregnancy remain a public health concern.ObjectiveTo determine the associations between iron status and birth outcomes of pregnant women attending antenatal clinic at a regional hospital in Bloemfontein.MethodsIn this cross-sectional study of 427 pregnant women, blood was taken to analyze biomarkers of anaemia (haemoglobin), iron status (ferritin and soluble transferrin receptor) and inflammation (C-reactive protein and α-1-acid glycoprotein). A questionnaire was used to collect information about birth outcomes (birth weight and gestational age at birth), HIV exposure, sociodemographics, iron supplement intake, and maternal dietary iron intake using a validated quantified food frequency questionnaire.ResultsThe median (Q1, Q3) weeks of gestation of participants was 32 (26, 36) at enrolment. Anaemia, iron deficiency (ID), ID anaemia (IDA) and ID erythropoiesis (IDE) were present in 42%, 31%, 19% and 9.8% of participants, respectively. Median (Q1, Q3) dietary and supplemental iron intake during pregnancy was 16.8 (12.7, 20.5) mg/d and 65 (65, 65) mg/d, respectively. The median (max-min) total iron intake (diet and supplements) was 81 (8.8-101.8) mg/d, with 88% of participants having a daily intake above the tolerable upper intake level of 45 mg/d. No significant associations of anaemia and iron status with low birth weight and prematurity were observed. However, infants born to participants in the third hemoglobin (Hb) quartile (Hb > 11.3–12.2 g/dL) had a shorter gestation by 1 week than those in the fourth Hb quartile (Hb > 12.2 g/dL) (p = 0.009). Compared to pregnant women without HIV, women with HIV had increased odds of being anaemic (OR:2.14, 95%CI: 1.41, 3.247), having ID (OR:2.19, 95%CI: 1.42, 3.37), IDA (OR:2.23, 95%CI: 1.36, 3.67), IDE (OR:2.22, 95%CI: 1.16, 4.22) and delivering prematurely (OR:2.39, 95%CI: 1.01, 5.64).ConclusionIn conclusion, anaemia, ID, and IDA were prevalent in this sample of pregnant women, despite the reported intake of prescribed iron supplements, with HIV-infected participants more likely to be iron deficient and anaemic. Research focusing on the best formulation and dosage of iron supplementation to enhance iron absorption and status, and compliance to supplementation is recommended, especially for those living with HIV infection.Graphical

Absorption, Anti-inflammatory, Antioxidant, and Cardioprotective Impacts of a Novel Fasting Mimetic Containing Spermidine, Nicotinamide, Palmitoylethanolamide, and Oleoylethanolamide: A Pilot Dose-Escalation Study in Healthy Young Adult Men

This pilot dose-escalation study evaluated the absorption and metabolism of a novel fasting mimetic formulation containing spermidine, nicotinamide, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) taken as oral supplements in young adults. Five healthy men consumed a standardized breakfast, followed by control (wheat flour) or low, medium, or high doses of supplements containing spermidine, nicotinamide, PEA, and OEA 2 h later. Blood was drawn at 0, 1, 2, and 4 h after the supplement (2, 3, 4, and 6 h postprandial). Plasma concentrations of spermidine, 1-methylnicotinamide (1-MNA), PEA and OEA were quantified by LC-MS. The secretion of tumor necrosis factor alpha (TNF-α) and production of reactive oxygen species (ROS) by stimulated macrophages incubated with plasma, and cholesterol efflux capacity (CEC) of plasma were analyzed. Plasma 1-MNA, PEA and OEA concentrations increased after supplement intake (P < 0.05). Spermidine concentrations decreased in the control arm (P < 0.05) but not the supplement arms. Net incremental area under the curve for TNF-α and ROS in stimulated macrophages decreased when incubated with plasma following supplement intake (P < 0.05). Intake of the combined supplements showed they were bioavailable and increased in plasma in a dose-dependent manner, and provide preliminary data showing enhanced plasma anti-inflammatory and antioxidant functions.This trial was registered at clinicaltrials.gov (NCT05017428).

Environmental sustainability and nutritional quality of different diets considering nutritional adequacy

This study examines how four diets change nutritionally and environmentally when the diets are nutritionally adjusted. Data on individual Belgian diets of omnivores (n = 131), pescovegetarians (n = 159), vegetarians (n = 494), and vegans (n = 78) were obtained, called non-adjusted diets. We assessed if diets met energy and nutrient intake requirements and calculated the Alternative Healthy Eating Index (AHEI)-2010. The environmental impact was evaluated by a cradle-to-grave life cycle assessment considering all midpoint indicators of the Environmental Footprint 3.0 and expressing the impact per “daily food and supplement intake by one Belgian adult”. The individual dietary intakes were adjusted nutritionally to meet the recommended energy and nutrition intakes using a quadratic programming algorithm. All diets had a significantly improved AHEI score but also a significantly increased water use (WU) when adjusting. The omnivore's diet demonstrated a significantly decreased carbon footprint (CF) while it significantly (except for vegans) raised for the restrictive diets due to adjustment. The omnivorous diet had the greatest improvements in AHEI (15.4), while WU increased the most among all diets (3.7 m3), primarily due to elevated fruit intake. The CF was reduced with 1.2 kg CO2 due to decreased red meat consumption. The AHEI of the vegan diet improved the second most of all diets (13.2) due to the intake of omega-3 supplements, while its WU rose the least of all diets (2.4 m3), and its CF barely increased (0.1 kg CO2-eq). The AHEI improvements of the vegetarian diet were similar to those of the vegan diet (12.5), while the one of the pescovegetarian diet was limited (3.5). The (pesco)vegetarian diet had an increase in WU (2.5 and 2.7 m3) and the highest increase in the CF (0.3 kg CO2-eq). Since nutritionally adjusted diets do not lead to similar nutritional and environmental improvements, this research highlights the need to assess both metrics.

Associations of pregnancy dietary quality and diversity with childhood celiac disease

Background and objectiveHigh gluten and low dietary fiber in pregnancy intake is associated with an increased risk of celiac disease in the child. Early life higher dietary quality is suggested to reduce the subsequent risk of celiac disease. The aim was to investigate associations of pregnancy dietary quality and diversity with child risk of celiac disease (CeD). MethodsIn The Norwegian Mother, Father and Child Cohort Study, 85,122 mother-child pairs had available data from a validated pregnancy food frequency questionnaire. Pregnancy dietary quality and diversity were estimated by a Pregnancy Healthy Eating Index, (mean 99.3, SD 9.9, range 48.8-128.3), and a Diet Diversity Score (mean 7.0, SD 1.0, range 1.6-9.8), respectively. Child CeD was captured by >2 diagnostic codes in the Norwegian Patient Registry. Logistic regression was used to estimate associations between pregnancy dietary quality, diversity and child CeD, adjusted for socio-economic factors and parents CeD (adjusted odds ratio [aOR], 95% confidence intervals [CI]). CeD-susceptible HLA haplotypes (DQ2/DQ8) were present in 30,718 (45.5%). ResultsUp to mean age 16.0 (SD 1.8, 12.4-19.8) years, 1,363 (1.6%) children were diagnosed with CeD. Lower as well as higher pregnancy dietary quality associated with a reduced risk of CeD in the child (<5th percentile aOR=0.67, 95%CI 0.48-0.93, >95th percentile aOR=0.71, 95%CI 0.52-0.98, respectively, non-linear squared term p= 0.011). Analyses on genetically susceptible children, adjustments for pregnancy iron supplementation, gluten, and dietary fiber intake, and child early life dietary quality, gluten intake and iron supplementation, supported the finding. Pregnancy dietary diversity was not associated with child CeD (aOR=1.00, 95%CI 0.94-1.07/score) ConclusionsIn this population-based study, lower as well as higher pregnancy dietary quality associated with a reduced risk of CeD diagnosis in the child. In contrast, no such association was observed with maternal dietary diversity.

Diabetes and Dietary Proteins-Protein Supplement Intake

Diabetes is a growing global health issue, with diet playing a crucial role in prevention and management. Protein, an essential nutrient for growth, repair, and metabolism, can significantly influence diabetes risk and control. High-protein diets, especially those rich in animal proteins, have been linked to increased risk of type 2 diabetes, while plant-based proteins may offer protective benefits. Studies suggest that excessive animal protein intake, particularly from red and processed meats, can increase diabetes risk due to higher saturated fat content. Conversely, plant-based proteins, such as soy, tofu, and nuts, are associated with improved insulin sensitivity and reduced inflammation. Protein supplements—especially whey and soy proteins—are known to help maintain muscle mass and improve metabolic indicators. However, the evidence supporting these benefits remains limited, and excessive protein intake may increase risks of other negative effects, such as impaired kidney function. Therefore, caution is advised when using these supplements. A balanced approach that emphasizes plant-based proteins while moderating animal protein intake is recommended for diabetes prevention and management. Future research should focus on personalized dietary strategies for optimal health outcomes.

Impact of Tocopherol Supplementation on Clinical Parameters of Periodontal Disease: A Systematic Review and Meta-Analysis.

Background and Objectives: The significance of periodontal disease as a public health issue prompts the exploration of effective treatments, including the potential use of tocopherol (Vitamin E) due to its anti-inflammatory and antioxidant properties. Materials and Methods: The PICO statement (Population, Intervention, Comparator, Outcome) was as follows: In patients with periodontal disease, does tocopherol (Vitamin E) supplementation compared to no supplementation or insufficient Vitamin E intake improve clinical outcomes such as gingival inflammation, pocket depth, and clinical attachment levels? This study searched through PubMed, Scopus, and Web of Science up to June 2024 focused on studies involving human subjects with various forms of periodontal disease, analyzing the impact of tocopherol through dietary or supplementary intake. Primary outcomes evaluated included improvements in gingival inflammation, pocket depth, and clinical attachment levels, with data synthesis conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality assessment and risk of bias were meticulously performed for the included observational studies and randomized controlled trials. Results: The meta-analysis incorporated 8 studies that were used for data extraction, totaling 12,832 patients, revealing a heterogeneous response to tocopherol supplementation, with a pooled odds ratio for efficacy in reducing periodontal disease severity at about 0.97 (95% CI: 0.96-0.98). Noteworthy findings indicated a statistically significant increase in clinical attachment loss and pocket depth with odds ratios ranging from 1.15 to 9.33 when Vitamin E was insufficient. However, the considerable heterogeneity (I2 = 88.35%) underscores variations in tocopherol's effectiveness across different populations and study designs. Conclusions: While tocopherol supplementation shows a modest benefit in managing periodontal disease, particularly in reducing clinical attachment levels and pocket depth, the variability in outcomes emphasizes the necessity for more research to establish standardized treatment protocols and dosages.