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Key PointsMicronutrient Assessment, Deficiencies, and InterventionsInquiry about the usual dietary pattern, with a focus on the omission of specific foods that can increase the risk of inadequate intake of micronutrients, is an important part of the assessment of micronutrient status.Micronutrient deficiencies, especially those identified on the basis of laboratory assessment, are generally uncommon in the United States.In addition to low dietary intake, certain clinical factors (e.g., malabsorption, intestinal surgery, alcoholism, some medications, anorexia, and pernicious anemia) increase the risk of micronutrient deficiency.Dietary and biochemical assessments are complementary, and there are reasons why they may not always be in agreement.Because national data on micronutrient intakes and status are collected cross-sectionally, it is difficult to determine the extent to which deficiencies are causal factors for chronic diseases and poor health.Randomized, controlled trials are needed to test the benefits of supplementation, but few of these trials have shown clear benefits in the United States.Future research should include more sensitive and informative methods of assessment for micronutrient deficiencies, such as “omics,” to detect effects on metabolism, gene expression, and proteins.

Vitamin B 12 (B12; also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. Clinical B12 deficiency with classic haematological and neurological manifestations is relatively uncommon. However, subclinical deficiency affects between 2.5% and 26% of the general population depending on the definition used, although the clinical relevance is unclear. B12 deficiency can affect individuals at all ages, but most particularly elderly individuals. Infants, children, adolescents and women of reproductive age are also at high risk of deficiency in populations where dietary intake of B12-containing animal-derived foods is restricted. Deficiency is caused by either inadequate intake, inadequate bioavailability or malabsorption. Disruption of B12 transport in the blood, or impaired cellular uptake or metabolism causes an intracellular deficiency. Diagnostic biomarkers for B12 status include decreased levels of circulating total B12 and transcobalamin-bound B12, and abnormally increased levels of homocysteine and methylmalonic acid. However, the exact cut-offs to classify clinical and subclinical deficiency remain debated. Management depends on B12 supplementation, either via high-dose oral routes or via parenteral administration. This Primer describes the current knowledge surrounding B12 deficiency, and highlights improvements in diagnostic methods as well as shifting concepts about the prevalence, causes and manifestations of B12 deficiency. Vitamin B 12 (also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. In this Primer, Green et al . describe the causes, consequences and management of vitamin B 12 deficiency.

Maternal and child undernutrition is highly prevalent in low-income and middle-income countries, resulting in substantial increases in mortality and overall disease burden. In this paper, we present new analyses to estimate the effects of the risks related to measures of undernutrition, as well as to suboptimum breastfeeding practices on mortality and disease. We estimated that stunting, severe wasting, and intrauterine growth restriction together were responsible for 2·2 million deaths and 21% of disability-adjusted life-years (DALYs) for children younger than 5 years. Deficiencies of vitamin A and zinc were estimated to be responsible for 0·6 million and 0·4 million deaths, respectively, and a combined 9% of global childhood DALYs. Iron and iodine deficiencies resulted in few child deaths, and combined were responsible for about 0·2% of global childhood DALYs. Iron deficiency as a risk factor for maternal mortality added 115 000 deaths and 0·4% of global total DALYs. Suboptimum breastfeeding was estimated to be responsible for 1·4 million child deaths and 44 million DALYs (10% of DALYs in children younger than 5 years). In an analysis that accounted for co-exposure of these nutrition-related factors, they were together responsible for about 35% of child deaths and 11% of the total global disease burden. The high mortality and disease burden resulting from these nutrition-related factors make a compelling case for the urgent implementation of interventions to reduce their occurrence or ameliorate their consequences.

Plant-based diets may increase the risk of vitamin B12 deficiency due to limited intake of animal-source foods, while dietary folate increases when adhering to plant-based diets. In this cross-sectional study, we evaluated the B12 and folate status of Norwegian vegans and vegetarians using dietary B12 intake, B12 and folic acid supplement use, and biomarkers (serum B12 (B12), plasma total homocysteine (tHcy), plasma methylmalonic acid (MMA) and serum folate). Vegans (n 115) and vegetarians (n 90) completed a 24-h dietary recall and a FFQ and provided a non-fasting blood sample. cB12, a combined indicator for evaluation of B12 status, was calculated. B12 status was adequate in both vegans and vegetarians according to the cB12 indicator; however 4 % had elevated B12. Serum B12, tHcy, MMA concentrations and the cB12 indicator (overall median: 357 pmol/l, 9·0 µmol/l, 0·18 µmol/l, 1·30 (cB12)) did not differ between vegans and vegetarians, unlike for folate (vegans: 25·8 nmol/l, vegetarians: 21·6 nmol/l, P = 0·027). Serum B12 concentration < 221 pmol/l was found in 14 % of all participants. Vegetarians revealed the highest proportion of participants below the recommended daily intake of 2 µg/d including supplements (40 v. 18 %, P < 0·001). Predictors of higher serum B12 concentrations were average daily supplement use and older age. Folate deficiency (< 10 nmol/l) was uncommon overall (< 2·5 %). The combined indicator cB12 suggested that none of the participants was B12-depleted; however, low serum B12 concentration was found in 14 % of the participants. Folate concentrations were adequate, indicating adequate folate intake in Norwegian vegans and vegetarians.

Indigenous knowledge and healing practices endure today, despite colonial policies and continued systematic oppression. Exemplary Indigenous-led movements that center on traditional Indigenous knowledge have become an important feature of the Canadian medical landscape, promoting cultural activities, self-determination, governance, language, medicine and wellness. Here, Allen et al analyze unique and innovative Indigenous-led health partnerships in Canada, considering the benefits that such partnerships can hold for physicians, Indigenous communities and Canadian society more broadly.

Type 2 Diabetes Mellitus (T2DM) is a primary cause of death in Belize, a low-income country with the highest rates in Central and South America. As many people in Belize cannot consistently access biomedical treatment, a reality that was exacerbated by the COVID-19 pandemic, plant medicine usage is estimated to have increased in recent years. This exploratory study seeks to understand which plants are being used, patterns of usage, and the state of patient-provider communication around this phenomenon. Implementing a Constructivist Grounded Theory qualitative design, the research team conducted 35 semi-structured interviews with adults living with T2DM, 25 informant discussions, and participant observation with field notes between February 2020 and September 2021. Data analysis followed systematized thematic coding procedures using Dedoose analytic software and iterative verification processes. The findings revealed that 85.7% of participants used plants in their T2DM self-management. There were three main usage patterns, namely, exclusive plant use (31.4%), complementary plant use (42.9%), and minimal plant use (11.4%), related to factors impacting pharmaceutical usage. Almost none of participants discussed their plant medicine usage with their health care providers. Plant species are outlined, as are patients' reasons for not disclosing usage to providers. There are implications for the advancement of understanding ethnobotanical medicine use for T2DM self-management and treatment in Belize and beyond.

Globally, almost 15 million infants are born prematurely each year, disproportionately affecting low and middle-income countries. In the absence of mother's milk, the World Health Organization recommends using donor human milk (DHM) due to its protective effect against necrotizing enterocolitis, a life-threatening intestinal disorder. The use of DHM is increasing globally, with many low and middle-income countries integrating donor milk banks into their public health strategies to reduce neonatal mortality, yet very little is known about the nutritional composition of DHM. Additional knowledge gaps include how DHM composition is influenced by milk banking practices, and whether preterm nutrient recommendations are achieved when DHM is used with commercially available fortifiers. We designed a multi-site study with eight geographically diverse milk bank partners in high, middle, and low-income settings that will examine and compare a broad range of nutrients and bioactive factors in human milk from 600 approved milk bank donors around the world to create comprehensive, geographically diverse nutrient profiles for DHM. We will then simulate the random pooling of 2 to 10 donors to evaluate the impact of pooling as a potential strategy for milk banks to manage nutrient variability in DHM. Finally, we will evaluate whether commercially available fortifiers meet nutrient recommendations when used with DHM. We expect that results from this study will improve nutritional care globally for the growing number of preterm infants who receive donor human milk.

While thiamin and riboflavin in breast milk have been analyzed for over 50 years, less attention has been given to the different forms of each vitamin. Thiamin-monophosphate (TMP) and free thiamin contribute to total thiamin content; flavin adenine-dinucleotide (FAD) and free riboflavin are the main contributors to total riboflavin. We analyzed milk collected at 2 (n = 258) or 6 (n = 104), and 24 weeks (n = 362) from HIV-infected Malawian mothers within the Breastfeeding, Antiretrovirals and Nutrition (BAN) study, randomly assigned at delivery to lipid-based nutrient supplements (LNS) or a control group, to investigate each vitamer's contribution to total milk vitamin content and the effects of supplementation on the different thiamin and riboflavin vitamers at early and later stages of lactation, and obtain insight into the transport and distribution of these vitamers in human milk. Thiamin vitamers were derivatized into thiochrome-esters and analyzed by high-performance liquid-chromatography-fluorescence-detection (HPLC-FLD). Riboflavin and FAD were analyzed by ultra-performance liquid-chromatography-tandem-mass-spectrometry (ULPC-MS/MS). Thiamin-pyrophosphate (TPP), identified here for the first time in breast milk, contributed 1.9-4.5% to total thiamin. Free thiamin increased significantly from 2/6 to 24 weeks regardless of treatment indicating an active transport of this vitamer in milk. LNS significantly increased TMP and free thiamin only at 2 weeks compared to the control: median 170 versus 151 μg/L (TMP), 13.3 versus 10.5 μg/L (free thiamin, p<0.05 for both, suggesting an up-regulated active mechanism for TMP and free thiamin accumulation at early stages of lactation. Free riboflavin was consistently and significantly increased with LNS (range: 14.8-19.6 μg/L (LNS) versus 5.0-7.4 μg/L (control), p<0.001), shifting FAD:riboflavin relative amounts from 92-94:6-8% to 85:15%, indicating a preferred secretion of the free form into breast milk. The continuous presence of FAD in breast milk suggests an active transport and secretion system for this vitamer or possibly formation of this co-enymatic form in the mammary gland.

Vitamin B (B12; also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. Clinical B12 deficiency with classic haematological and neurological manifestations is relatively uncommon. However, subclinical deficiency affects between 2.5% and 26% of the general population depending on the definition used, although the clinical relevance is unclear. B12 deficiency can affect individuals at all ages, but most particularly elderly individuals. Infants, children, adolescents and women of reproductive age are also at high risk of deficiency in populations where dietary intake of B12-containing animal-derived foods is restricted. Deficiency is caused by either inadequate intake, inadequate bioavailability or malabsorption. Disruption of B12 transport in the blood, or impaired cellular uptake or metabolism causes an intracellular deficiency. Diagnostic biomarkers for B12 status include decreased levels of circulating total B12 and transcobalamin-bound B12, and abnormally increased levels of homocysteine and methylmalonic acid. However, the exact cut-offs to classify clinical and subclinical deficiency remain debated. Management depends on B12 supplementation, either via high-dose oral routes or via parenteral administration. This Primer describes the current knowledge surrounding B12 deficiency, and highlights improvements in diagnostic methods as well as shifting concepts about the prevalence, causes and manifestations of B12 deficiency.