Zinc deficiency is common in Japan, yet awareness on this disorder is lacking. The Japanese Society of Clinical Nutrition recently issued the Japan’s Practical Guideline for Zinc Deficiency 2018 setting forth criteria for diagnosing zinc deficiency, i.e., (a) one or more symptoms of zinc deficiency or low serum alkaline phosphatase, (b) ruling out other diseases, (c) low serum zinc, and (d) alleviation of symptoms upon zinc administration. Serum zinc <60 μg/dL and 60–80 μg/dL indicate zinc deficiency and marginal deficiency, respectively. Zinc deficiency symptoms vary and include dermatitis and taste disorders among others. Zinc administration improves taste in 50–82% of patients suffering from taste disorders (a common symptom of zinc deficiency). Effects of zinc administration do not appear immediately, and therapy should be continued for at least three months. Zinc deficiency often accompanies various diseases and conditions. Here, we focus on inflammatory bowel diseases and liver cirrhosis. As zinc deficiency enhances intestinal inflammation via macrophage activation, we discuss the pathological mechanism for inflammation and zinc deficiency in the context of IBD. Zinc deficiency can also lead to a nitrogen metabolic disorder in patients with liver cirrhosis. Zinc supplementation can improve not only the ammonia metabolism, but also the protein metabolism. We also discuss directions for future studies of zinc deficiency.

The incidence of pancreatic cancer (PC) continues to increase in the world, while most patients are diagnosed with advanced stages and survive <12 months. This poor prognosis is attributable to difficulty of early detection. Here we developed and evaluated a multivariate index composed of plasma free amino acids (PFAAs) for early detection of PC. We conducted a cross-sectional study in multi-institutions in Japan. Fasting plasma samples from PC patients (n = 360), chronic pancreatitis (CP) patients (n = 28), and healthy control (HC) subjects (n = 8372) without apparent cancers who were undergoing comprehensive medical examinations were collected. Concentrations of 19 PFAAs were measured by liquid chromatography–mass spectrometry. We generated an index consisting of the following six PFAAs: serine, asparagine, isoleucine, alanine, histidine, and tryptophan as variables for discrimination in a training set (120 PC and matching 600 HC) and evaluation in a validation set (240 PC, 28 CP, and 7772 HC). Several amino acid concentrations in plasma were significantly altered in PC. Plasma tryptophan and histidine concentrations in PC were particularly low, while serine was particularly higher than that of HC. The area under curve (AUC) based on receiver operating characteristic (ROC) curve analysis of the resulting index to discriminate PC from HC were 0.89 [95% confidence interval (CI), 0.86–0.93] in the training set. In the validation set, AUCs based on ROC curve analysis of the PFAA index were 0.86 (95% CI, 0.84–0.89) for all PC patients versus HC subjects, 0.81 (95% CI, 0.75–0.86) for PC patients from stage IIA to IIB versus HC subjects, and 0.87 (95% CI, 0.80–0.93) for all PC patients versus CP patients. These findings suggest that the PFAA profile of PC was significantly different from that of HC. The PFAA index is a promising biomarker for screening and diagnosis of PC.

The capacity to metabolize proteins is closely related to the hepatic functional reserve in patients with chronic liver disease, and hypoalbuminemia and hyperammonemia develop along with hepatic disease progression. Zinc deficiency, which is frequently observed in patients with chronic liver disease, significantly affects protein metabolism. Ornithine transcarbamylase is a zinc enzyme involved in the urea cycle. Its activity decreases because of zinc deficiency, thereby reducing hepatic capacity to metabolize ammonia. Because the glutamine-synthesizing system in skeletal muscles compensates for the decrease in ammonia metabolism, hyperammonemia does not develop in the early stages of chronic liver disease. However, branched-chain amino acids (BCAAs) are consumed with the increase in glutamine-synthesizing system reactions, leading to a decreased capacity to synthesize proteins, including albumin, due to amino acid imbalance. Upon further disease progression, skeletal muscle mass decreases because of nutritional deficiency, as well as the further decreased capacity to metabolize ammonia in the liver, whereby the capacity to detoxify ammonia reduces as a whole, resulting in hyperammonemia. BCAA supplementation therapy for nutritional deficiency in liver cirrhosis improves survival by correcting amino acid imbalance via recovery of the capacity to synthesize albumin, while zinc supplementation therapy improves the capacity to metabolize ammonia in the liver. Here, the efficacy of a combination of BCAA and zinc preparation for nutritional deficiency in liver cirrhosis, as well as its theoretical background, was reviewed.

The Prevalence and Implication of Zinc Deficiency in Patients With Chronic Liver Disease

Pancreatic cancer (PC) is the fourth leading cause of cancer-related death with a 5-year survival rate less than 10%. In the absence of effective screening methods, such as blood markers, most clinical diagnoses of PC are made at an advanced stage. However, early stage PC is associated with a more favorable five-year survival rate of 85.8% for stage 0, and 68.7% for stage IA. Transabdominal ultrasound (US) is frequently used as a first-line diagnostic tool in the clinical setting and a preferred modality for routine medical evaluations for asymptomatic individuals. Recently published Japanese data show that most PCs diagnosed in early stage had US findings, such as dilated main pancreatic ducts or pancreas cysts. For surveillance of high-risk individuals, such as those with an intraductal papillary mucinous neoplasm (IPMN), US is an ideal modality in terms of its non-invasive and cost-effective nature. However, the diagnostic performance of ultrasound varies greatly by the operator’s experience and the patient’s condition. This article reviews the present situation of early diagnosis of pancreatic cancer by US, along with tips for improving visualization of the pancreas.