Safe Intake Level Research Articles

Scientific opinion on the tolerable upper intake level for iron.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for iron. Systematic reviews were conducted to identify evidence regarding high iron intakes and risk of chronic diseases, adverse gastrointestinal effects and adverse effects of iron supplementation in infancy, young childhood and pregnancy. It is established that systemic iron overload leads to organ toxicity, but no UL could be established. The only indicator for which a dose-response could be established was black stools, which reflect the presence of large amounts of unabsorbed iron in the gut. This is a conservative endpoint among the chain of events that may lead to systemic iron overload but is not adverse per se. Based on interventions in which black stools did not occur at supplemental iron intakes of 20-25 mg/day (added to a background intake of 15 mg/day), a safe level of intake for iron of 40 mg/day for adults (including pregnant and lactating women) was established. Using allometric scaling (body weight0.75), this value was scaled down to children and adolescents and safe levels of intakes between 10 mg/day (1-3 years) and 35 mg/day (15-17 years) were derived. For infants 7-11 months of age who have a higher iron requirement than young children, allometric scaling was applied to the supplemental iron intakes (i.e. 25 mg/day) and resulted in a safe level of supplemental iron intake of 5 mg/day. This value was extended to 4-6 month-old infants and refers to iron intakes from fortified foods and food supplements, not from infant and follow-on formulae. The application of the safe level of intake is more limited than a UL because the intake level at which the risk of adverse effects starts to increase is not defined.

Safety of soy leghemoglobin from genetically modified Komagataella phaffii as a food additive.

The EFSA Panel on Food Additive and Flavourings (FAF Panel) provides a scientific opinion on the safety of soy leghemoglobin from genetically modified Komagataella phaffii as a food additive in accordance with Regulation (EC) No 1331/2008. The proposed food additive, LegH Prep, is intended to be used as a colour in meat analogue products. The yeast Komagataella phaffii strain MXY0541 has been genetically modified to produce soy leghemoglobin; the safety of the genetic modification is under assessment by the EFSA GMO Panel (EFSA-GMO-NL-2019-162). The amount of haem iron provided by soy leghemoglobin from its proposed uses in meat analogue products is comparable to that provided by similar amounts of different types of meat. The exposure to iron from the proposed food additive, both at the mean and 95th percentile exposure, will be below the 'safe levels of intake' established by the NDA Panel for all population groups. Considering that the components of the proposed food additive will be digested to small peptide, amino acids and haem B; the recipient (non GM) strain qualifies for qualified presumption of safety status; no genotoxicity concern has been identified and no adverse effects have been identified at the highest dose tested in the available toxicological studies, the Panel concluded that there was no need to set a numerical acceptable daily intake (ADI) and that the food additive does not raise a safety concern at the proposed use in food category 12.9 and maximum use level. The Panel concluded that the use of soy leghemoglobin from genetically modified Komagataella phaffii MXY0541 as a new food additive does not raise a safety concern at the proposed use and use level. This safety evaluation of the proposed food additive remains provisional subject to the ongoing safety assessment of the genetic modification of the production strain by the GMO Panel (EFSA-GMO-NL-2019-162).

The efficacy of Carbamylglutamate impacts the nutritional management of patients with N-Acetylglutamate synthase deficiency

BackgroundThe autosomal recessive disorder N-acetylglutamate synthase (NAGS) deficiency is the rarest defect of the urea cycle, with an incidence of less than one in 2,000,000 live births. Hyperammonemic crises can be avoided in individuals with NAGS deficiency by the administration of carbamylglutamate (also known as carglumic acid), which activates carbamoyl phosphatase synthetase 1 (CPS1). The aim of this case series was to introduce additional cases of NAGS deficiency to the literature as well as to assess the role of nutrition management in conjunction with carbamylglutamate therapy across new and existing cases.MethodsWe conducted retrospective chart reviews of seven cases of NAGS deficiency in the US and Canada, focusing on presentation, diagnosis, medication management, nutrition management, and outcomes.ResultsFive new and two previously published cases were included. Presenting symptoms were consistent with previous reports. Diagnostic confirmation via molecular testing varied in protocol across cases, with consecutive single gene tests leading to long delays in diagnosis in some cases. All patients responded well to carbamylglutamate therapy, as indicated by normalization of plasma ammonia and citrulline, as well as urine orotic acid in patients with abnormal levels at baseline. Although protein restriction was not prescribed in any cases after carbamylglutamate initiation, two patients continued to self-restrict protein intake. One patient experienced two episodes of hyperammonemia that resulted in poor long-term outcomes. Both episodes occurred after a disruption in access to carbamylglutamate, once due to insurance prior authorization requirements and language barriers and once due to seizure activity limiting the family’s ability to administer carbamylglutamate.ConclusionsFollow-up of patients with NAGS deficiency should include plans for illness and for disruption of carbamylglutamate access, including nutrition management strategies such as protein restriction. Carbamylglutamate can help patients with NAGS deficiency to liberalize their diets, but the maximum safe level of protein intake to prevent hyperammonemia is not yet known. Patients using this medication should still monitor their diet closely and be prepared for any disruptions in medication access, which might require immediate dietary adjustments or medical intervention to prevent hyperammonemia.

Использование витаминов группы В в профилактических и лечебных дозах при сахарном диабете 2-го типа

Polyhypovitaminosis is a risk factor for many diseases. Adequate dietary intake of vitamins may help prevent/reduce the risk of progression of several diseases, including type 2 diabetes (T2D). Objective. To analyze the sufficiency of B vitamins and efficacy of their administration in patients with T2D depending on the dose. Vitamin deficiencies typical for patients with T2D worsen the course of the disease and increase the risk of complications. Higher intake of vitamins B1, B2 and folate is associated with a lower risk of T2D, and higher intake of folate and vitamin B6 is associated with a lower risk of cardiovascular diseases in patients with T2D. Higher intake of vitamin B6 by individuals with T2D is associated with a lower incidence of diabetic retinopathy. In T2D patients, low levels of the coenzyme form of vitamin B6 and high serum levels of 4-pyridoxic acid increase the risk of all-cause mortality. Patients with diabetic retinopathy have significantly reduced levels of vitamin B12. The incidence of vitamin B2 deficiency based on serum levels is found in approximately 30–40% of patients with T2D and diabetic nephropathy. Metformin administration worsens vitamin B12 supply and increases the risk of T2D complications. The need to eliminate vitamin deficiencies and improve the sufficiency of B vitamins is undeniable. There are prophylactic and therapeutic doses of vitamins. Continuous intake of multivitamin supplements with a complete set of all B vitamins in prophylactic doses consistent with the recommended daily intake (RDI) will reduce the risk of T2D progression. Administration of B vitamins during 1 month to 5 years in therapeutic doses well above the RDI results in improvement of carbohydrate metabolism, antioxidant and clinical status in patients with T2D, but may lead to undesirable effects. Conclusion. When prescribing B vitamins to T2D patients, it is recommended to distinguish between prophylactic doses of vitamins that meet the body’s needs and can and should be taken continuously, and therapeutic doses, that are close to the upper safe intake level and may cause adverse reactions. Key words: type 2 diabetes, B vitamins, sufficiency, prophylactic and therapeutic doses of vitamins

Safety of HelixComplex snail mucus (HSM) as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on HelixComplex Snail Mucus (HSM) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of snail mucus collected from Helix aspersa maxima and is proposed to be used by adults as a food supplement. The data provided by the applicant about the composition and stability of the NF together with the report of the subchronic toxicity study were overall considered unsatisfactory. The Panel noted inconsistencies in the reporting of the certificates of analysis and of the data on the subchronic toxicity provided by the applicant. Owing to these deficiencies, the Panel cannot establish a safe intake level of the NF. The Panel concludes that the safety of the NF has not been established.

Scientific opinion on the tolerable upper intake level for manganese.

Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for manganese. Systematic reviews of the literature of human and animal data were conducted to assess evidence regarding excess manganese intake (including authorised manganese salts) and the priority adverse health effect, i.e. manganese-induced neurotoxicity. Available human and animal studies support neurotoxicity as a critical effect, however, data are not sufficient and suitable to characterise a dose-response relationship and identify a reference point for manganese-induced neurotoxicity. In the absence of adequate data to establish an UL, estimated background dietary intakes (i.e. manganese intakes from natural dietary sources only) observed among high consumers (95th percentile) were used to provide an indication of the highest level of intake where there is reasonable confidence on the absence of adverse effects. A safe level of intake of 8 mg/day was established for adults ≥ 18 years (including pregnant and lactating women) and ranged between 2 and 7 mg/day for other population groups. The application of the safe level of intake is more limited than an UL because the intake level at which the risk of adverse effects starts to increase is not defined.

Treatment and management for children with urea cycle disorder in chronic stage.

Urea cycle disorder (UCD) is a group of inherited metabolic diseases with high disability or fatality rate, which need long-term drug treatment and diet management. Except those with Citrin deficiency or liver transplantation, all pediatric patients require lifelong low protein diet with safe levels of protein intake and adequate energy and lipids supply for their corresponding age; supplementing essential amino acids and protein-free milk are also needed if necessary. The drugs for long-term use include nitrogen scavengers (sodium benzoate, sodium phenylbutyrate, glycerol phenylbutyrate), urea cycle activation/substrate supplementation agents (N-carbamylglutamate, arginine, citrulline), etc. Liver transplantation is recommended for pediatric patients not responding to standard diet and drug treatment, and those with severe progressive liver disease and/or recurrent metabolic decompensations. Gene therapy, stem cell therapy, enzyme therapy and other novel technologies may offer options for treatment in UCD patients. The regular biochemical assessments like blood ammonia, liver function and plasma amino acid profile are needed, and physical growth, intellectual development, nutritional intake should be also evaluated for adjusting treatment in time.

Total Protein Intake in Patients with PKU: Adequacy Evaluation According to the European PKU Guidelines from 2017

In PKU, the protein requirements are contentious. In 2018, we evaluated the protein intake in patients with PKU. Ninety-nine early treated patients aged 19.3 ± 8.2 years (54% males) were studied. A total of 24 had hyperphenylalaninemia (HPA), 48 mild and 27 classical PKU. All had an annual nutritional status evaluation. A total of 83% were on diet therapy only, and 17% were on diet with tetrahydrobiopterin therapy. Anthropometry, metabolic control and nutritional intake [total protein (TP, g/kg), natural protein (NP, g/kg), protein equivalent from protein substitutes (PE, g/kg)] were collected. TP adequacy (TPA) was calculated as a % of WHO (2007) safe levels of protein intake. Results were compared with the European PKU Guidelines (EPG). The median % contribution NP of TP intake was 53% [31–100]. Most patients (78%) had a TP intake above the EPG recommendations. The median TPA was 171% [146–203], with 79% [51–165] from NP and 84% [0–109] from PE. A TPA of 100–140% was observed in 16 (16%) patients. Only n = 6 (6%) patients had a TPA < 100%. These results emphasize the heterogeneity of PKU. More research is needed to understand the necessity of a single protein recommendation for all, as a ‘one-size-fits-all’ solution might not be appropriate.

Thiamin (Vitamin B1) – A scoping review for Nordic Nutrition Recommendations 2023

Only a few studies have explored relationships between thiamine intake and function, and a few studies have examined the effects of supplements on various clinical or biochemical outcomes. None of these studies, however, makes a useful contribution to understanding requirements in healthy populations. The requirement of thiamine relates to energy and carbohydrate intake. Clinical signs of deficiency have been observed at intakes below 0.5 mg/day, which corresponds to 0.05 mg/MJ. In other studies, thiamine excretion in the urine and normalisation of enzyme activity were normalised at intakes of 0.07–0.08 mg/MJ. The lower limit of intake thus estimates at 0.05 mg/MJ. It has not been possible to set a safe upper intake level for thiamine due to a lack of data.
 Studies on pregnant and lactating women indicate a higher requirement as assessed by biochemical parameters. A few studies indicate that thiamine utilisation is impaired among elderly subjects.

De-novo exposure assessment of heavy metals in commercially important fresh and dried seafood: Safe for human consumption

The heavy metals (HMs) in seafood are alarming due to their biomagnification in the food chain. The concentrations of As, Cd, Hg, Pb, Cr, and Ni in both fresh and dried fish were quantified, and the potential exposure and safe intake levels for human consumption were assessed by the European Commission (EC) and the Food Safety Standard Authority of India (FSSAI). HMs concentrations ranged from 0.003 mg/kg (Cr) to 2.08 mg/kg for (As) and 0.007 mg/kg (Hg) to 2.76 mg/kg (As). Cd, Hg, and Pb levels in fresh and dried fish were below the maximum residue limits (MRLs) set by the EC and FSSAI, which were 0.1 mg/kg, 0.5 mg/kg, and 0.3 mg/kg, respectively. Cr and As concentrations were also below the MRLs of 12 mg/kg and 76 mg/kg for aquatic products specified by FSSAI. The concentration of HMs in fresh and dried fish was found in the order of As > Cr > Ni > Pb > Cd > Hg and As > Cd > Cr > Ni > Pb > Hg, while the fresh and dried fishes contained HMs in the following order: E. areolatus > S. longiceps > L.lentjen > S. barracuda > E. affinis > S. javus and DA > DS > DR > DB > DSF. The metal pollution index (MPI) validates seafood is HMs free, while the single (Pi) and Nemerow integrated pollution index (Pnw) indicate that concentrations of Cd and As in fresh and dried fish have exceeded the threshold value. The target hazard quotient (THQ<1), hazard index (HI < 1), and target cancer risk (TCR<10−4) indicate that there are no non-carcinogenic and carcinogenic risks through the consumption of seafood and seafood products collected from the Tuticorin coast and marketed at the domestic and international levels. The preliminary findings emphasize the importance of formulating domestic legislation/government initiatives to promote seafood and its consumption. The attainment of this objective shall be facilitated by examining the levels of persistent organic pollutants (POPs) in seafood and evaluating its potential risk to consumers.

Functional Ingredients for specialized Foods: Issues to be Addressed

Review was carried out using the RSCI, Google Scholar, Pubmed, and ReserchGate databases. When biologically active substances (BAS) are used as functional ingredients in the composition of specialized food products (SPP) of dietary therapeutic and dietary preventive nutrition, the problems of choosing their dose arise. There are epidemiological data on the level of consumption of BAS with food, an associative relationship between the level of consumption of biologically active substances and the risk of diseases, as well as the results of assessing clinical efficacy are described. The content of BAS is regulated by regulatory documents that establish an adequate and upper permissible level of consumption as part of the SPP.The purpose of the review is to assess the level of dietary intake of curcumin, carotenoids, β-glucans, and taurine, and to compare the doses allowed for use as part of the SPP with doses that provide a clinical effect. An analysis of literature data showed that the consumption of taurine with a normaldiet is 50–400 mg, curcumin – 10–1500 mg, β-carotene – 0.8–10 mg, lycopene – 5–10.5 mg, lutein – 1–3 mg, zeaxanthin – 0.1–0.6 mg, cereal β-glucans – 0.7–2.8 g, mushroom β-glucans – 0.9–1.8 g. With the exception of β-glucans, especially cereals, these values do not exceed the current upper allowable consumption level as part of the SPP. The results of clinical trials have shown that effective daily doses for lutein are 15 mg, taurine are 1.5–3 g, curcumin are 300–1600 mg, cereal β-glucans are 3–8 g, mushroom and yeast β-glucans are about 1 g. These data indicate the need to increase the amount of BAS as part of the SPP of dietary therapeutic nutrition to clinically justified values. At the same time, the given data indicate the expediency of differentiating the SPP, depending on the doses of BAS, into 2 categories: SPP for preventive and SPP for therapeutic action. SPP for dietary preventive nutrition is necessary to compensate the insufficient intake of essential micronutrients and achieve an adequate level of consumption of BAS, which will reduce the risk of alimentary-dependent diseases. In order to provide a clinical effect in pathological conditions, dietary therapeutic SPP should contain higher doses of biologically active substances that exceed the adequate intake level, but do not reach the upper safe intake level.

Safety of β-hydroxybutyrate salts as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on β‐hydroxybutyrate (BHB) salts as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of sodium, magnesium and calcium BHB salts, and is proposed to be used by adults as a food ingredient in a number of food categories and as food supplement. The data provided by the applicant about the identity, the production process and the compositional data of the NF over the course of the risk assessment period were overall considered unsatisfactory. The Panel noted inconsistencies in the reporting of the test item used in the subchronic toxicity study and human studies provided by the applicant. Owing to these deficiencies, the Panel cannot establish a safe intake level of the NF. The Panel concludes that the safety of the NF has not been established.

Preliminary assessment of heavy metals intake via food in CKDu affected Uddanam region of Srikakulam, Andhra Pradesh, India

ABSTRACT The present study aimed to assess metal/heavy metal intake by the population via food environment of the Uddanam region, a hotspot for chronic kidney disease of uncertain aetiology (CKDu) in India. The food samples included rice/paddy, marine/freshwater fish, green gram/black gram (whole), and green leafy vegetables (GLVs, i.e. amaranth/spinach). These were analysed for metal/heavy metal (chromium, nickel, copper, arsenic, lead, magnesium, calcium, aluminium, manganese, iron, zinc, barium, cadmium, mercury, and uranium) content using standard procedures. The total heavy metal intake was calculated as a sum of the intake from each food source. The daily dietary intake was compared to safe intake levels (from the Institute of Medicine of the National Academies and National Institute of Nutrition). The intake was higher than safe levels for lead, chromium, and manganese. It is advisable to reduce heavy metal exposure by adopting agricultural practices and public health interventions in terms of diet.

Different Dose of Sucrose Consumption Divergently Influences Gut Microbiota and PPAR-γ/MAPK/NF-κB Pathway in DSS-Induced Colitis Mice.

Sugar reduction and sugar control are advocated and gaining popularity around the world. Sucrose, as the widely consumed ingredient in our daily diet, has been reported a relation to gastrointestinal diseases. However, the role of sucrose in inflammatory bowel disease remains controversial. Hence, our study aimed to elucidate the potential role of three doses of sucrose on DSS-induced colitis in C57BL/6 mice and the underlying mechanisms. The results showed that low-dose sucrose intervention alleviated colitis in mice, reducing the expression of inflammatory cytokines and repairing mucosal damages. In contrast, high-dose sucrose intervention exacerbated colitis. Furthermore, three doses of sucrose administration markedly altered gut microbiota composition. Notably, the low-dose sucrose restored microbial dysfunction and enhanced the production of short chain fatty acids (SCFAs). Specifically, the abundance of SCFAs-producing bacteria Faecalibaculum, Bacteroides, and Romboutsia were increased significantly in the LOW group. Consistently, PPAR-γ, activated by SCFAs, was elevated in the LOW group, thereby inhibiting the MAPK/NF-κB pathway. Together, our study demonstrates the differential effects of sucrose on colitis at different doses, providing a scientific basis for measuring and modifying the safe intake level of sugar and providing favorable evidence for implementing sugar reduction policies.

Reconsidering the Tolerable Upper Levels of Zinc Intake among Infants and Young Children: A Systematic Review of the Available Evidence.

Safe upper levels (UL) of zinc intake for children were established based on either (1) limited data from just one study among children or (2) extrapolations from studies in adults. Resulting ULs are less than amounts of zinc consumed by children in many studies that reported benefits of zinc interventions, and usual dietary zinc intakes often exceed the UL, with no apparent adverse effects. Therefore, existing ULs may be too low. We conducted a systematic bibliographic review of studies among preadolescent children, in which (1) additional zinc was provided vs. no additional zinc provided, and (2) the effect of zinc on serum or plasma copper, ceruloplasmin, ferritin, transferrin receptor, lipids, or hemoglobin or erythrocyte super-oxide dismutase were assessed. We extracted data from 44 relevant studies with 141 comparisons. Meta-analyses found no significant overall effect of providing additional zinc, except for a significant negative effect on ferritin (p = 0.001), albeit not consistent in relation to the zinc dose. Interpretation is complicated by the significant heterogeneity of results and uncertainties regarding the physiological and clinical significance of outcomes. Current zinc ULs should be reassessed and potentially revised using data now available for preadolescent children and considering challenges regarding interpretation of results.

Predictors of 25-hydroxyvitamin D concentrations during pregnancy: A longitudinal analysis in the Brazilian Amazon.

To determine predictors of 25-hydroxyvitamin D3 (25(OH)D3) concentrations (25th, 50th, and 75th percentiles) in the third trimester of pregnancy. Data on sociodemographic, obstetric, lifestyle and pregnancy characteristics, including serum 25(OH)D3 and retinol, were collected among 448 pregnant women who participated in the Maternal and Child Health and Nutrition in Acre, Brazil (MINA-Brazil Study) in Cruzeiro do Sul, Brazilian Amazon (latitude 7°S). Simultaneous-quantile regression was fitted to prospectively assess predictors at the 25th, 50th and 75th percentiles of 25(OH)D3 concentrations. In the third trimester, 25(OH)D3 <50 nmol/L was observed in 26% of pregnant women. Exposure to the Amazonian dry season during follow-up and vitamin D status ≥75 nmol/L in the second trimester of pregnancy were positively associated with 25(OH)D3 concentrations in the third trimester. Pregnant women who were the main providers of family income presented lower 25(OH)D3 concentrations (50th and 75th percentiles: -15 nmol/L, 95%CI -24; -3, p = 0.02, and -22 nmol/L, 95%CI -36; -7, p = 0.004, respectively), as well as those with sustained vitamin A insufficiency (25th and 50th percentiles: -27 nmol/L, 95%CI -40; -15, p < 0.001, and -17 nmol/L, 95%CI -33; -1, p = 0.04, respectively). Sun protection practices had a smaller negative impact on 25(OH)D3, restricted to participants whose concentrations were at the 25th percentile of the distribution. Seasonality and vitamin A status were important predictors of 25(OH)D3 concentrations in the third trimester. Adequate exposure to sunlight and dietary sources of vitamin A within safe intake levels may help ensuring a good nutritional status of vitamin D during pregnancy.

Tolerable upper intake level for dietary sugars.

Following a request from five European Nordic countries, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was tasked to provide scientific advice on a tolerable upper intake level (UL) or a safe level of intake for dietary (total/added/free) sugars based on available data on chronic metabolic diseases, pregnancy‐related endpoints and dental caries. Specific sugar types (fructose) and sources of sugars were also addressed. The intake of dietary sugars is a well‐established hazard in relation to dental caries in humans. Based on a systematic review of the literature, prospective cohort studies do not support a positive relationship between the intake of dietary sugars, in isocaloric exchange with other macronutrients, and any of the chronic metabolic diseases or pregnancy‐related endpoints assessed. Based on randomised control trials on surrogate disease endpoints, there is evidence for a positive and causal relationship between the intake of added/free sugars and risk of some chronic metabolic diseases: The level of certainty is moderate for obesity and dyslipidaemia (> 50–75% probability), low for non‐alcoholic fatty liver disease and type 2 diabetes (> 15–50% probability) and very low for hypertension (0–15% probability). Health effects of added vs. free sugars could not be compared. A level of sugars intake at which the risk of dental caries/chronic metabolic diseases is not increased could not be identified over the range of observed intakes, and thus, a UL or a safe level of intake could not be set. Based on available data and related uncertainties, the intake of added and free sugars should be as low as possible in the context of a nutritionally adequate diet. Decreasing the intake of added and free sugars would decrease the intake of total sugars to a similar extent. This opinion can assist EU Member States in setting national goals/recommendations.

Recommendations on phenylketonuria in Turkey.

Phenylketonuria (PKU), is an autosomal recessive disease leading to the conversion defect of phenylalanine (Phe) into tyrosine. Severe neurocognitive and behavioral outcomes are observed in untreated cases. The present paper aims to review clinical experiences and expert recommendations in diagnosis, treatment, and follow-up of pediatric PKU patients in Turkey. Two advisory board meetings were held in the year 2016 and 2017 with contributions of four leading experts in this field, and an online update meeting was held for final decisions about statements, and conclusions in January 2021. Considering management gaps in diagnosis, treatment, and follow-up of PKU, discussion points are defined. The Committee members then reviewed the Turkish and general literature and the final statements were formulated. The diagnostic cut-off for dried blood spots should remain at 2 mg/dl. Treatment cut-off value is acceptable at 6 mg/dl. Compliance with an ideal follow-up list is strongly recommended. Total protein intake should not be limited. Age-related safe levels of protein intake should be encouraged with an additional 40% from L-amino acids supplements, a 20% compensatory factor to account for the digestibility and utilization of amino acids from the supplement, and a further 20% compensation to optimize Phe control. Cognitive impairment and intelligence quotient evaluations should be performed at least twice before 3 years of age. In pregnant women, the target Phe level should be < 5 mg/dl, and they should be followed-up weekly in the first trimester, then every 2 weeks after organogenesis. Novel pharmacological treatments are promising, but some of them have limitations for our country. Early diagnosis and treatment initiation; determination and standardization of diagnostic and treatment thresholds; treatment modalities and follow-up parameters are significant steps in treating PKU in the long term. PKU follow-up is a dynamic process with uncertainties and differences in clinical practice.

Effects of alcohol consumption on viral hepatitis B and C.

The liver is the main target organ for hepatitis viruses and the vital organ for alcohol metabolism. These two factors of viral hepatitis and alcohol abuse in combination can exert dual harmful actions, leading to enhanced damage to the liver. Epidemiological studies have revealed a higher prevalence of hepatitis C virus (HCV) infection among alcoholics than the general population. The interaction of alcohol with viral hepatitis [e.g., hepatitis B virus (HBV), HCV] and the underlying mechanisms are not fully understood. The effects of alcohol on viral hepatitis include promoted viral replication, weakened immune response, and increased oxidative stress. Clinically, alcohol abuse is correlated with an increased risk of developing end-stage liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B and C, suggesting that the combination of alcohol and HBV/HCV lead to more severe liver damage. The influence of mild to moderate alcohol drinking on the HBV-induced liver fibrosis, cirrhosis, and hepatocellular carcinoma among patients infected with HBV remains unclear. Unlike HBV infected patients, no safe level of alcohol intake has been established for patients with HCV. Even light to moderate alcohol use can exert a synergistic effect with viral hepatitis, leading to the rapid progression of liver disease. Furthermore, interferon-based therapy is less effective in alcohol drinkers than in control patients, even after abstinence from alcohol for a period of time. Therefore, abstaining from alcohol is highly recommended to protect the liver, especially in individuals with HBV/HCV infection, to improve the clinical efficacy of antiviral treatment and prevent the rapid progression of chronic viral hepatitis.

Temporal Trends in Dietary Sodium Intake Among Adults Aged ≥19 Years - United States, 2003-2016.

Hypertension, which can be brought on by excess sodium intake, affects nearly one half of U.S. adults and is a major risk factor for heart disease, the leading cause of death in the United States (1). In 2019, the National Academies of Sciences, Engineering, and Medicine (NASEM) established the Chronic Disease Risk Reduction (CDRR) intake, a chronic-disease-specific recommendation for dietary sodium of 2,300 mg/day. Reducing daily sodium to CDRR intake is expected to reduce chronic disease risk among healthy persons, primarily by lowering blood pressure (2). Although the 2019 sodium CDRR intake is equivalent in number to the 2005 Tolerable Upper Limit (UL) released by NASEM (then known as the Institute of Medicine), the UL was intended to provide guidance on safe intake levels, not to serve as an intake goal (2). To describe excess sodium intake in the context of the CDRR intake goal, this report analyzed National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2016 to yield temporal trends in usual sodium intake >2,300 mg/day and in mean sodium intake, unadjusted and adjusted for total energy intake, among U.S. adults aged ≥19 years. The percentage of U.S. adults with sodium intake above CDRR intake was 87.0% during 2003-2004 and 86.7% during 2015-2016. Among U.S. adults overall, no significant linear trend was noted from 2003 to 2016 in unadjusted or energy intake-adjusted mean sodium intake. Small, significant declines were observed in mean usual sodium intake among some groups (adults aged 19-50 years, non-Hispanic White adults, adults experiencing obesity, and adults without hypertension). However, after energy adjustment, only adults aged ≥71 years and Mexican American adults demonstrated significant change in usual sodium intake. Many U.S. adults might be at risk for chronic disease associated with sodium intake above CDRR intake, and efforts to lower sodium intake could improve population cardiovascular health. The results of this report support enhanced efforts to reduce population sodium intake and cardiovascular disease risk, including the Food and Drug Administration's (FDA's) recently released guidance for the reduction of sodium in the commercially processed, packaged, and prepared food supply.