Evaluating the effect of non-invasive force feedback on prosthetic grasp force modulation in participants with and without limb loss.

Grasping an object is one of the most common and complex actions performed by humans. The human brain can adapt and update the grasp dynamics through information received from sensory feedback. Prosthetic hands can assist with the mechanical performance of grasping, however currently commercially available prostheses do not address the disruption of the sensory feedback loop. Providing feedback about a prosthetic hand's grasp force magnitude is a top priority for those with limb loss. This study tested a wearable haptic system, i.e., the Clenching Upper-Limb Force Feedback device (CUFF), which was integrated with a novel robotic hand (The SoftHand Pro). The SoftHand Pro was controlled with myoelectrics of the forearm muscles. Five participants with limb loss and nineteen able-bodied participants completed a constrained grasping task (with and without feedback) which required modulation of the grasp to reach a target force. This task was performed while depriving participants of incidental sensory sources (vision and hearing were significantly limited with glasses and headphones). The data were analyzed with Functional Principal Component Analysis (fPCA). CUFF feedback improved grasp precision for participants with limb loss who typically use body-powered prostheses as well as a sub-set of able-bodied participants. Further testing, that is more functional and allows participants to use all sensory sources, is needed to determine if CUFF feedback can accelerate mastery of myoelectric control or would benefit specific patient sub-groups.

Opinions on noninvasive sensory feedback of upper limb prosthetic users.

BACKGROUND: Restoring touch perception for individuals with upper extremity limb loss is an ambitious task. It is important to understand how persons with upper limb loss think this would be best achieved. METHODS: An anonymous online survey was developed to obtain data from prosthetic users. Participants ranked the perceived acceptability and effectiveness of noninvasive sensory feedback to areas of intact sensation not typically involved in sensory feedback (i.e., the arm). The focus was on 4 main types of haptic information-object contact, proprioception, surface texture, and grasp force-as well as how best to convey those senses with various stimuli. The users were asked to grade themselves in certain tasks and then analyze which tasks would be improved with sensory feedback. Associations were explored between demographic characteristics and interest in sensory feedback. RESULTS: Nationally, prostheses providers sent more than 2000 email invitations to the online survey and received 142 unique responses. Responses indicated interest in sensory feedback through prosthetic limbs by individuals with upper limb loss. The most popular pairing of haptic information with sensory substitution was grasp force paired with gentle vibration. Tasks that most persons taking the survey agreed would benefit from sensory feedback were zipping a jacket, tying shoes, buttoning a shirt, and using a cup. No difference was observed in interest between sex and employment status, but a significant decrease (P = .004) was seen in interest among participants with more years of prosthetic use. DISCUSSION: The results from this national survey of upper extremity prosthetic users can be used to help guide the development of noninvasive sensory feedback options.

Iodine in Foods and Dietary Supplements: A Collaborative Database Developed by NIH, FDA and USDA.

Data on the iodine content of foods and dietary supplements are needed to develop general population intake estimates and identify major contributors to intake. Samples of seafood, dairy products, eggs, baked products, salts, tap water, other foods and beverages, and dietary supplements were collected according to established sampling plans of the U.S. Department of Agriculture (USDA) and the U.S. Food and Drug Administration (FDA). Samples were assayed for iodine content using inductively coupled plasma mass spectrometry with rigorous quality control measures. The food data were released through a collaboration of USDA, FDA, and the Office of Dietary Supplements-National Institutes of Health (ODS-NIH) as the USDA, FDA, and ODS-NIH Database for the Iodine Content of Common Foods at www.ars.usda.gov/mafcl. Iodine data for dietary supplements are available in the ODS-USDA Dietary Supplement Ingredient Database and the ODS Dietary Supplement Label Database. Data from the iodine databases linked to national dietary survey data can provide needed information to monitor iodine status and develop dietary guidance for the general U.S. population and vulnerable subgroups. This iodine information is critical for dietary guidance development, especially for those at risk for iodine deficiency (i.e., women of reproductive age and young children).

Contemporary Outcomes of Transfemoral Amputation After Total Knee Arthroplasty.

BACKGROUND: Transfemoral amputation (TFA) is a salvage procedure for unreconstructable failed total knee arthroplasty (TKA). Prior studies have reported poor outcomes, patient survival, and prosthetic use. The purpose of this study was to analyze patient outcomes and prosthetic utilization in a contemporary group of patients undergoing TFA in the setting of a TKA. METHODS: We reviewed 112 patients undergoing TFA with a prior TKA. Indications for amputation and postoperative functional measures were captured through chart review. Patients were contacted by survey to assess the quality of life. The mean follow-up after TFA was 4 years. RESULTS: Amputations were performed for a chronically infected TKA (n = 87, 78%) and an ischemic limb without signs of an infected TKA (n = 22, 20%). The 10-year survival after TFA was 21%. Of the patients not lost to follow-up, 53 (47%) patients were fitted for a prosthesis. Patients who underwent a TFA after the year 2000 were more likely to be fit for a prosthesis (odds ratio 7.27, P < .01); however, patients were likely to be ambulatory before TFA than after TFA (odds ratio 3.68, P < .01). After TFA, the mean 12-Item Short Form Survey scores for the mental and physical components were 54 ± 13 and 34 ± 7, with no difference in scores between patients fitted for a prosthesis and those who were not (P > .05). CONCLUSION: Patients undergoing a TFA after TKA due to failure of the TKA are more likely to be fit for a prosthesis; however, they reported no better quality of life and satisfaction compared with patients not fit for a prosthesis. LEVELS OF EVIDENCE: Level III, Therapeutic.

Do Multivitamin/Mineral Dietary Supplements for Young Children Fill Critical Nutrient Gaps?

BACKGROUND: Nearly a third of young US children take multivitamin/mineral (MVM) dietary supplements, yet it is unclear how formulations compare with requirements. OBJECTIVE: Describe the number and amounts of micronutrients contained in MVMs for young children and compare suggested amounts on product labels to micronutrient requirements. DESIGN: Cross-sectional. SETTING: All 288 MVMs on the market in the United States in the National Institutes of Health's Dietary Supplement Label Database in 2018 labeled for children 1 to <4 years old. MAIN OUTCOME MEASURES: Number of MVM products and amounts per day of micronutrients in each product suggested on labels compared with requirements represented by age-appropriate Daily Values (DV). Micronutrients of public health concern identified by the Dietary Guidelines for Americans (DGA) 2015-2020 (DGA 2015) and DGA 2020-2025 (DGA 2020) or those of concern for exceeding the upper tolerable intake levels. STATISTICAL ANALYSES: Number of products and percent DV per day provided by each micronutrient in each product. RESULTS: The 288 MVMs contained a mean of 10.1 ± 2.27 vitamins and 4.59 ± 2.27 minerals. The most common were, in rank order, vitamins C, A, D, E, B6, B12; zinc, biotin, pantothenic acid, iodine, and folic acid. For micronutrients denoted by the DGA 2015 and DGA 2020 of public health concern, 56% of the 281 products containing vitamin D, 4% of the 144 with calcium, and none of the 60 containing potassium provided at least half of the DV. The upper tolerable intake level was exceeded by 49% of 197 products with folic acid, 17% of 283 with vitamin A, and 14% of 264 with zinc. Most MVMs contained many of 16 other vitamins and minerals identified in national surveys as already abundant in children's diets. CONCLUSIONS: A reexamination of the amounts and types of micronutrients in MVMs might consider formulations that better fill critical gaps in intakes and avoid excess.

High intraluminal pressure promotes vascular inflammation via caveolin-1.

The aetiology and progression of hypertension involves various endogenous systems, such as the renin angiotensin system, the sympathetic nervous system, and endothelial dysfunction. Recent data suggest that vascular inflammation may also play a key role in the pathogenesis of hypertension. This study sought to determine whether high intraluminal pressure results in vascular inflammation. Leukocyte adhesion was assessed in rat carotid arteries exposed to 1 h of high intraluminal pressure. The effect of intraluminal pressure on signaling mechanisms including reactive oxygen species production (ROS), arginase expression, and NFĸB translocation was monitored. 1 h exposure to high intraluminal pressure (120 mmHg) resulted in increased leukocyte adhesion and inflammatory gene expression in rat carotid arteries. High intraluminal pressure also resulted in a downstream signaling cascade of ROS production, arginase expression, and NFĸB translocation. This process was found to be angiotensin II-independent and mediated by the mechanosensor caveolae, as caveolin-1 (Cav1)-deficient endothelial cells and mice were protected from pressure-induced vascular inflammatory signaling and leukocyte adhesion. Cav1 deficiency also resulted in a reduction in pressure-induced glomerular macrophage infiltration in vivo. These findings demonstrate Cav1 is an important mechanosensor in pressure-induced vascular and renal inflammation.

Analytical Challenges and Metrological Approaches to Ensuring Dietary Supplement Quality: International Perspectives.

The increased utilization of metrology resources and expanded application of its' approaches in the development of internationally agreed upon measurements can lay the basis for regulatory harmonization, support reproducible research, and advance scientific understanding, especially of dietary supplements and herbal medicines. Yet, metrology is often underappreciated and underutilized in dealing with the many challenges presented by these chemically complex preparations. This article discusses the utility of applying rigorous analytical techniques and adopting metrological principles more widely in studying dietary supplement products and ingredients, particularly medicinal plants and other botanicals. An assessment of current and emerging dietary supplement characterization methods is provided, including targeted and non-targeted techniques, as well as data analysis and evaluation approaches, with a focus on chemometrics, toxicity, dosage form performance, and data management. Quality assessment, statistical methods, and optimized methods for data management are also discussed. Case studies provide examples of applying metrological principles in thorough analytical characterization of supplement composition to clarify their health effects. A new frontier for metrology in dietary supplement science is described, including opportunities to improve methods for analysis and data management, development of relevant standards and good practices, and communication of these developments to researchers and analysts, as well as to regulatory and policy decision makers in the public and private sectors. The promotion of closer interactions between analytical, clinical, and pharmaceutical scientists who are involved in research and product development with metrologists who develop standards and methodological guidelines is critical to advance research on dietary supplement characterization and health effects.

Disintegration and Dissolution Testing of Green Tea Dietary Supplements: Application and Evaluation of United States Pharmacopeial Standards.

Approved performance quality tests are lacking in the United States Pharmacopeia (USP) for dietary supplements (DSs) containing green tea extracts. We evaluated the applicability of USP <2040 > general chapter protocols for disintegration and dissolution testing of botanicals to GT DSs. Of 28 single-ingredient GT DSs tested in 2 to 4 lots, 9 (32.1%) always passed the disintegration test, 8 (28.6%) always failed, and 11 (39.3%) showed inconsistent results. Of 34 multi-ingredient DSs tested in 2 lots, 21 (61.8%) passed and 8 (23.5%) failed in both lots, and 5 (14.7%) exhibited inconsistent performance. When stronger destructive forces were applied (disk added), all of the capsules that had failed initially, but not the tablets, passed. In dissolution testing, for the release of epigallocatechin-3-gallate (EGCG), only 6 of 20 single-ingredient DSs passed. Unexpectedly, with the addition of pepsin (prescribed by USP), only one additional DS passed. These results raise concerns that EGCG was not released properly from GT DS dosage forms. However, the general USP protocols may be inadequate for this botanical. More biorelevant destructive forces may be needed to break down capsules and tablets strengthened by the EGCG's interaction with shell material and to overcome the inhibition of digestive enzymes by EGCG.

Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory?

Cyclo-oxygenase (COX) inhibitors are among the most commonly used drugs in the western world for their anti-inflammatory and analgesic effects. However, they are also well-known to increase the risk of coronary events. This area is of renewed significance given alarming new evidence suggesting this effect can occur even with acute usage. This contrasts with the well-established usage of aspirin as a mainstay for cardiovascular prophylaxis, as well as overwhelming evidence that COX inhibition induces vasodilation and is protective for vascular function. Here, we present an updated review of the preclinical and clinical literature regarding the cardiotoxicity of COX inhibitors. While studies to date have focussed on the role of COX in influencing renal and vascular function, we suggest an interaction between prostanoids and T cells may be a novel factor, mediating elevated cardiovascular disease risk with NSAID use.

The Chemical Forms of Iron in Commercial Prenatal Supplements Are Not Always the Same as Those Tested in Clinical Trials.

In the US, 70% of pregnant women use an iron-containing prenatal supplement product; however, only 2.6% of pregnant women have iron-deficiency anemia and 16.3% are iron deficient. Yet, published data on the amounts and chemical forms of iron used in formulating these products are not available, although they are known to affect bioavailability. This information is especially important in comparing commercially available products with those that were tested in clinical trials. Our examination of nonprescription and prescription iron-containing prenatal supplement products in NIH's Dietary Supplement Label Database (DSLD) and DailyMed found the labeled amount of elemental iron ranged between 9 and 60 mg/serving in 148 nonprescription supplements and between 4.5 and 106 mg/serving in 101 prescription supplements. Ferrous fumarate was the preferred chemical form used in these products. In contrast, ferrous sulfate was the preferred chemical form of iron reported in the clinical trials summarized in a 2015 Cochrane Systematic review assessing the effects of daily oral iron supplements for pregnant women. Ferrous sulfate was not found on any prenatal supplement product label in the DSLD or DailyMed. The chemical forms of products on the market and those tested in clinical trials are dissimilar, and we believe this may have clinical implications. The findings raise several questions. Do outcomes in clinical trials correlate with the benefits and risks that might adhere to iron supplements with different iron formulations? Should the differences in chemical forms, their bioavailability, and safety profiles, be considered in greater depth when evaluating the effect of the various formulations on maternal iron nutriture? Should new clinical trials for pregnant and lactating women in the US use a form of iron not found in prenatal supplements sold in the US or should a more common form be used?

Y Chromosome, Hypertension and Cardiovascular Disease: Is Inflammation the Answer?

It is now becomingly increasingly evident that the functions of the mammalian Y chromosome are not circumscribed to the induction of male sex. While animal studies have shown variations in the Y are strongly accountable for blood pressure (BP), this is yet to be confirmed in humans. We have recently shown modulation of adaptive immunity to be a significant mechanism underpinning Y-chromosome-dependent differences in BP in consomic strains. This is paralleled by studies in man showing Y chromosome haplogroup is a significant predictor for coronary artery disease through influencing pathways of immunity. Furthermore, recent studies in mice and humans have shown that Y chromosome lineage determines susceptibility to autoimmune disease. Here we review the evidence in animals and humans that Y chromosome lineage influences hypertension and cardiovascular disease risk, with a novel focus on pathways of immunity as a significant pathway involved.

Plantar Ulcers and Neuropathic Arthropathies: Associated Diseases, Polyneuropathy Correlates, and Risk Covariates.

OBJECTIVE: To evaluate the associated diseases, polyneuropathy correlates, and risk covariates of neuropathic plantar ulcers (PUs) and neuropathic arthropathies (NAs). DESIGN: The authors conducted a retrospective, observational study over 3.5 years of 69 patients with neuropathy, NA, or PU seen in a wound clinic who also had a comprehensive neurologic evaluation and neurophysiologic testing. Comparisons were made to a population representative cohort of patients with diabetes mellitus (DM; n = 259). RESULTS: Of the 69 wound clinic patients, 32 had PUs, 14 had NAs, and 23 had both. Of the 61 adequately assessed patients, 37 (61%) had DM, 22 (36%) had no known associated disease, and 2 (3%) had hereditary sensory and autonomic neuropathy. Of the 37 patients with DM, 35 had distal polyneuropathy, and 2 did not. In 22 patients with chronic idiopathic axonal polyneuropathy, 20 had distal polyneuropathy. CONCLUSIONS: Although DM was the disease most commonly associated with PUs and NAs, chronic hyperglycemia may not have been the major underlying risk factor. The major risk covariates are sensation loss from polyneuropathy, old age, obesity, repetitive foot injury, and inadequate foot care or treatment. Physicians and other healthcare providers can help by identifying patients at risk and instituting measures such as adequate foot care to decrease these risks.

Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat.

Despite its well-known antithrombotic properties, the effect of aspirin on blood pressure (BP) and hypertension pathology is unclear. The hugely varying doses used clinically have contributed to this confusion, with high-dose aspirin still commonly used due to concerns about the efficacy of low-dose aspirin. Because prostaglandins have been shown to both promote and inhibit T-cell activation, we also explored the immunomodulatory properties of aspirin in hypertension. Although the common preclinical high dose of 100 mg/kg/d improved vascular dysfunction and cardiac hypertrophy, this effect was accompanied by indices of elevated adaptive immunity, renal T-cell infiltration, renal fibrosis, and BP elevation in stroke-prone spontaneously hypertensive rats and in angiotensin II-induced hypertensive mice. The cardioprotective effects of aspirin were conserved with a lower dose (10 mg/kg/d) while circumventing heightened adaptive immunity and elevated BP. We also show that low-dose aspirin improves renal fibrosis. Differential inhibition of the COX-2 isoform may underlie the disparate effects of the 2 doses. Our results demonstrate the efficacy of low-dose aspirin in treating a vast array of cardiovascular parameters and suggest modulation of adaptive immunity as a novel mechanism underlying adverse cardiovascular profiles associated with COX-2 inhibitors. Clinical studies should identify the dose of aspirin that achieves maximal cardioprotection with a new awareness that higher doses of aspirin could trigger undesired autoimmunity in hypertensive individuals. This work also warrants an evaluation of high-dose aspirin and COX-2 inhibitor therapy in sufferers of inflammatory conditions who are already at increased risk for cardiovascular disease.-Khan, S. I., Shihata, W. A., Andrews, K. L., Lee, M. K. S., Moore, X.-L., Jefferis, A.-M., Vinh, A., Gaspari, T., Dragoljevic, D., Jennings, G. L., Murphy, A. J., Chin-Dusting, J. P. F. Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat.

Chronic sympathetic driven hypertension promotes atherosclerosis by enhancing hematopoiesis.

Hypertension is a major, independent risk factor for atherosclerotic cardiovascular disease. However, this pathology can arise through multiple pathways, which could influence vascular disease through distinct mechanisms. An overactive sympathetic nervous system is a dominant pathway that can precipitate in elevated blood pressure. We aimed to determine how the sympathetic nervous system directly promotes atherosclerosis in the setting of hypertension. We used a mouse model of sympathetic nervous system-driven hypertension on the atherosclerotic-prone apolipoprotein E-deficient background. When mice were placed on a western type diet for 16 weeks, we showed the evolution of unstable atherosclerotic lesions. Fortuitously, the changes in lesion composition were independent of endothelial dysfunction, allowing for the discovery of alternative mechanisms. With the use of flow cytometry and bone marrow imaging, we found that sympathetic activation caused deterioration of the hematopoietic stem and progenitor cell niche in the bone marrow, promoting the liberation of these cells into the circulation and extramedullary hematopoiesis in the spleen. Specifically, sympathetic activation reduced the abundance of key hematopoietic stem and progenitor cell niche cells, sinusoidal endothelial cells and osteoblasts. Additionally, sympathetic bone marrow activity prompted neutrophils to secrete proteases to cleave the hematopoietic stem and progenitor cell surface receptor CXCR4. All these effects could be reversed using the ß-blocker propranolol during the feeding period. These findings suggest that elevated blood pressure driven by the sympathetic nervous system can influence mechanisms that modulate the hematopoietic system to promote atherosclerosis and contribute to cardiovascular events.

The SoftHand Pro: Functional evaluation of a novel, flexible, and robust myoelectric prosthesis.

Roughly one quarter of active upper limb prosthetic technology is rejected by the user, and user surveys have identified key areas requiring improvement: function, comfort, cost, durability, and appearance. Here we present the first systematic, clinical assessment of a novel prosthetic hand, the SoftHand Pro (SHP), in participants with transradial amputation and age-matched, limb-intact participants. The SHP is a robust and functional prosthetic hand that minimizes cost and weight using an underactuated design with a single motor. Participants with limb loss were evaluated on functional clinical measures before and after a 6-8 hour training period with the SHP as well as with their own prosthesis; limb-intact participants were tested only before and after SHP training. Participants with limb loss also evaluated their own prosthesis and the SHP (following training) using subjective questionnaires. Both objective and subjective results were positive and illuminated the strengths and weaknesses of the SHP. In particular, results pre-training show the SHP is easy to use, and significant improvement in the Activities Measure for Upper Limb Amputees in both groups following a 6-8 hour training highlights the ease of learning the unique features of the SHP (median improvement: 4.71 and 3.26 and p = 0.009 and 0.036 for limb loss and limb-intact groups, respectively). Further, we found no difference in performance compared to participant's own commercial devices in several clinical measures and found performance surpassing these devices on two functional tasks, buttoning a shirt and using a cell phone, suggesting a functional prosthetic design. Finally, improvements are needed in the SHP design and/or training in light of poor results in small object manipulation. Taken together, these results show the promise of the SHP, a flexible and adaptive prosthetic hand, and pave a path forward to ensuring higher functionality in future.

Y-chromosome lineage determines cardiovascular organ T-cell infiltration in the stroke-prone spontaneously hypertensive rat.

The essential role of the Y chromosome in male sex determination has largely overshadowed the possibility that it may exert other biologic roles. Here, we show that Y-chromosome lineage is a strong determinant of perivascular and renal T-cell infiltration in the stroke-prone spontaneously hypertensive rat, which, in turn, may influence vascular function and blood pressure (BP). We also show, for the first time to our knowledge, that augmented perivascular T-cell levels can directly instigate vascular dysfunction, and that the production of reactive oxygen species that stimulate cyclo-oxygenase underlies this. We thus provide strong evidence for the consideration of Y-chromosome lineage in the diagnosis and treatment of male hypertension, and point to the modulation of cardiovascular organ T-cell infiltration as a possible mechanism that underpins Y- chromosome regulation of BP.-Khan, S. I., Andrews, K. L., Jackson, K. L., Memon, B., Jefferis, A.-M., Lee, M. K. S., Diep, H., Wei, Z., Drummond, G. R., Head, G. A., Jennings, G. L., Murphy, A. J., Vinh, A., Sampson, A. K., Chin-Dusting, J. P. F. Y-chromosome lineage determines cardiovascular organ T-cell infiltration in the stroke-prone spontaneously hypertensive rat.

Vascular dysfunction in the stroke-prone spontaneously hypertensive rat is dependent on constrictor prostanoid activity and Y chromosome lineage.

Vascular dysfunction is a hallmark of hypertension and the strongest risk factor to date for coronary artery disease. As Y chromosome lineage has emerged as one of the strongest genetic predictors of cardiovascular disease risk to date, we investigated if Y chromosome lineage modulated this important facet in the stroke-prone spontaneously hypertensive rat (SHRSP) using consomic strains. Here, we show that vascular dysfunction in the SHRSP is attributable to differential cyclooxygenase (COX) activity with nitric oxide (NO) levels playing a less significant role. Measurement of prostacyclin, the most abundant product of COX in the vasculature, confirmed the augmented COX activity in the SHRSP aorta. This was accompanied by functional impairment of the vasodilatory prostacyclin (IP) receptor, while inhibition of the thromboxane (TP) receptor significantly ameliorated vascular dysfunction in the SHRSP, suggesting this is the downstream target responsible for constrictor prostanoid activity. Importantly, Y chromosome lineage was shown to modulate vascular function in the SHRSP through influencing COX activity, prostacyclin levels and IP dysfunction. Vascular dysfunction in the renal and intrarenal arteries was also found to be prostanoid and Y chromosome dependent. Interestingly, despite no apparent differences in agonist-stimulated NO levels, basal NO levels were compromised in the SHRSP aorta, which was also Y chromosome dependent. Thus, in contrast with the widely held view that COX inhibition is deleterious for the vasculature due to inhibition of the vasodilator prostacyclin, we show that COX inhibition abolishes vascular dysfunction in three distinct vascular beds, with IP dysfunction likely being a key mechanism underlying this effect. We also delineate a novel role for Y chromosome lineage in regulating vascular function through modulation of COX and basal NO levels.

Challenges in Developing Analytically Validated Laboratory-Derived Dietary Supplement Databases.

The Dietary Supplement Label Database (DSLD) is sponsored by the Office of Dietary Supplements (ODS) and the National Library of Medicine (NLM). It provides a searchable, free database of the contents of ∼65,000 supplement labels. A companion database of analytically verified product labels [the Dietary Supplement Ingredient Database (DSID)] was created by ODS, NLM, and the USDA. There are considerable challenges to populating both databases, but the DSID faces unique analytic chemistry challenges. This article describes the challenges to creating analytically verified marketplace surveys of dietary supplement (DS) product content claims for inclusion in public databases. Nutritionists and public health scientists require information on actual exposures to DS constituents because labeled content may not match labeled product content. Analytic verification of composition of DSs provides a link to actual exposure. A public database of analytically derived DS content was developed to provide more accurate estimates of dietary intake in population-based epidemiologic studies. The DSID has conducted surveys of several types of vitamin- and mineral-containing DSs. Results showing label content claims as analytically derived values are available in the current DSID. A recent pilot project explored the feasibility of adding botanical DS products to the DSID. Candidates for future botanical DSID studies will be based on sales volume, potential public health impacts, and the availability of validated analytic methods and reference materials. Databases like DSID and the DSLD are essential for researchers and clinicians to evaluate dietary ingredient intakes in population-based epidemiologic studies. Together, these databases provide a picture of the DS marketplace. The DSID provides an analytic survey of marketed DSs. However, selection of future botanical supplements for DSID evaluation involves analytic challenges. Even when appropriate resources are available, method selection and data evaluation are resource- and time-consuming.

Dietary Supplement Ingredient Database (DSID) and the Application of Analytically Based Estimates of Ingredient Amount to Intake Calculations.

OBJECTIVE: We describe the purpose of the Dietary Supplement Ingredient Database (DSID), the statistical methodology underlying online calculators of analytically verified supplement content estimates, and the application and significance of DSID label adjustments in nutritional epidemiology. BACKGROUND AND HISTORY: During dietary supplement (DS) manufacturing, many ingredients are added at higher than declared label amounts, but overages are not standardized among manufacturers. As a result, researchers may underestimate nutrient intakes from DSs. The DSID provides statistical tools on the basis of the results of chemical analysis to convert label claims into analytically predicted ingredient amounts. These adjustments to labels are linked to DS products reported in NHANES. RATIONALE: Tables summarizing the numbers of NHANES DS products with ingredient overages and below label content show the importance of DSID adjustments to labels for accurate intake calculations. RECENT DEVELOPMENTS: We show the differences between analytically based estimates and labeled content for vitamin D, calcium, iodine, caffeine, and omega-3 (n-3) fatty acids and their potential impact on the accuracy of intake assessments in large surveys. Analytical overages >20% of label levels are predicted for several nutrients in 50-99% of multivitamin-mineral products (MVMs) reported in NHANES: for iodine and selenium in adult MVMs, for iodine and vitamins D and E in children's MVMs, and for iodine, chromium, and potassium in nonprescription prenatal MVMs. Predicted overages of 10-20% for calcium can be applied to most MVMs and overages >10% for folic acid in the vast majority of adult and children's MVMs. FUTURE DIRECTIONS: DSID studies are currently evaluating ingredient levels in prescription prenatal MVMs and levels of constituents in botanical DSs. CONCLUSIONS: We estimate that the majority of MVM products reported in NHANES have significant overages for several ingredients. It is important to account for nonlabeled additional nutrient exposure from DSs to better evaluate nutritional status in the United States.