Many studies have investigated the relationships between vitamins and esophageal cancer (EC). Most of these studies focused on the roles of vitamins in the prevention and treatment of EC, and few studies have examined the changes in vitamin nutritional status and their influencing factors before and after chemotherapy for EC. Chemotherapy may have a considerable effect on EC patients’ vitamin levels and hematological indicators.

To research the nutritional status of multiple vitamins in EC patients during chemotherapy and to assess its clinical significance.

EC patients admitted to our center from July 2017 to September 2020 were enrolled in this study. Serum concentrations of nine vitamins (A, D, E, B₉, B₁₂, B₁, C, B₂ and B₆), hemoglobin, total protein, albumin, blood calcium, blood phosphorus concentrations and body mass index (BMI) were measured in all EC patients. The changes in nine vitamins, hematological indicators and BMI were compared before and after two cycles of chemotherapy. The possible influential factors were analyzed.

In total, 203 EC patients receiving chemotherapy were enrolled in this study. Varying degrees of vitamin A, D, C and B₂ deficiency and weight loss were found in these patients, and the proportions of vitamin B₂ and vitamin C deficiencies increased significantly after chemotherapy (both P < 0.05). Serum concentrations of vitamins A, C, B₂ and B₆ and BMI before and after chemotherapy were statistically significant (all P < 0.05). Multivariate analysis showed that vitamin A levels significantly differed between male and female EC patients, whereas vitamin D concentration significantly differed in EC patients in different stages (all P < 0.05). Correlations were observed between the changes in serum concentrations of vitamin A and C before and after two cycles chemotherapy and the change in BMI (P < 0.05). Hemoglobin, total protein, serum albumin and blood calcium concentrations significantly decreased in EC patients after chemotherapy (all P < 0.05), while the blood phosphorus level significantly increased after chemotherapy (P < 0.05). Using the difference in vitamin concentrations as the independent variables and the difference in BMI as the dependent variable, logistic regression analysis revealed statistically significant differences for vitamin A, vitamin D and vitamin C (F = 5.082, P = 0.002).

Vitamin A, D, C and B₂ were mainly deficient in patients with EC during chemotherapy. Multivitamin supplementation may help to improve the nutritional status, chemotherapy tolerance and efficacy.

Esophageal cancer (EC) is the ninth most commonly diagnosed cancer and the sixth leading cause of cancer death worldwide[1]. The incidence and mortality rates of EC are highly heterogeneous in terms of gender, histological type, geographic distribution and race[2]. The morbidity and mortality of EC in China are higher than the global averages[3]. Chemoradiotherapy remains the mainstay of treatment for patients with advanced EC. The most common complications during chemoradiotherapy in EC patients include weight loss, malnutrition, bone marrow suppression, electrolyte disturbances, hypoproteinemia and decreased quality of life[4-7]. Multiple vitamins are involved in the pathogenesis, progression and prognosis of tumors and are closely related to the tumor microenvironment. Vitamin testing is valuable in tumor patients as it can identify whether there is a specific vitamin deficiency and/or justify vitamin therapy. Most clinical studies have shown that vitamin nutritional status varies greatly in tumors of different systems[8]. Although many studies have investigated the relationships between vitamins B, A, D and C with EC, most of these studies focused on the roles of vitamins in the prevention and treatment of EC. Few studies have examined the changes in vitamin nutritional status and their influencing factors before and after chemotherapy for EC.

Many vitamins have antitumor effects and are closely related to the occurrence, progression, prognosis and recovery of tumors. Vitamin supplementation can lower the risk of tumorigenesis and prevent abnormal DNA methylation changes in tumor cells[9]. With the advances in nutritional therapy in China, nutritional screenings, assessments and interventions have increasingly been applied in tumor patients. The standardized nutritional therapies involve three major macronutrients including carbohydrates, proteins and fats and have specific requirements on micronutrients. Nutritional therapy for tumor patients provides nutrients and energy and focuses on the metabolism-regulating roles of nutrients[10]. Vitamin supplementation is a common nutritional therapy for tumor patients in clinical practice. Serum vitamin levels vary among patients with different tumors. Zhang et al[11] analyzed the vitamin nutritional status of approximately 1000 hospitalized tumor patients and found that vitamin B1 concentrations were low in patients with digestive system tumors such as EC and gastric cancer. A study on postoperative nutritional deficiencies in patients with EC or gastric cancer revealed that the incidence of ferritin, folic acid, vitamin B₁₂ and vitamin D deficiencies was 42.86%, 9.52%, 6.35% and 36.67%, respectively, and the vitamin levels were significantly improved after nutritional interventions[12]. In another study[13], most patients with advanced tumors had vitamin (particularly vitamins D, B₆ and C) deficiency symptoms during palliative care, and further analysis revealed a correlation between the degree of vitamin deficiency and clinical discomfort in these patients. Most vitamins were found to be negatively associated with the risk of colorectal and gastric cancer in addition to EC in an observational study, yet interventional treatment failed to demonstrate a clear preventive effect in these malignancies [14].

In the current study, we analyzed the effects of chemotherapeutic drugs on EC patients’ vitamin levels and hematological indicators by detecting the changes in nine vitamins and hematological indicators (e.g., hemoglobin, total protein, serum albumin and electrolytes) before and after chemotherapy, with an attempt to provide evidence for clinical vitamin supplementation and nutritional therapies. Our findings may be valuable for the implementation of tailored nutritional interventions, which will help to reduce chemotherapy-related complications, alleviate treatment resistance and improve chemotherapy efficacy.

It was found that EC patients had different degrees of vitamin deficiency during chemotherapy, and the hemoglobin, total protein, serum albumin concentration and blood calcium concentration significantly decreased after chemotherapy. In addition, the proportions of patients with weight loss, anemia and hypoproteinemia also significantly increased. Our subjects were most deficient in vitamin B₂ and vitamin C followed by vitamins A and D.

In the current study, EC patients undergoing chemotherapy were most deficient in vitamin B₂ (31.53% and 46.80% before and after chemotherapy, respectively), and vitamin B₂ concentration significantly decreased after chemotherapy (P < 0.05). Vitamin B₁, B₉, B₁₂ and B₆ deficiency or excess was not found in any of our EC patients. A comparison of vitamin levels before and after chemotherapy suggested that vitamin B₆ concentrations decreased significantly after chemotherapy but were still within the normal range. It has been reported that B vitamin intake is correlated with the risk of EC. Appropriate supplementation with vitamins B₆ and B₉ (also known as folate) can reduce the risk, while higher intake of vitamin B₁₂ may increase the risk[15,16]. A study of residents in Yanting County, Sichuan Province, a high-incidence area of EC in China, found that riboflavin intake was markedly deficient, and riboflavin supplements in high-risk groups reduced the incidence of EC[17]. In a multicenter study in China, whole blood riboflavin was tested in 764 EC patients (and in controls), and the analysis revealed that whole blood riboflavin levels were not significantly correlated with the prevalence of EC. However, high whole blood riboflavin level was more favorable for the survival of elderly EC patients aged 50-70 yrs[18]. Therefore, B vitamin supplementation in EC patients undergoing chemotherapy is beneficial to improve vitamin nutritional status and reduce complications.

In our research, the proportion of vitamin C deficiency cases was 23.65% and 34.48%, before and after chemotherapy, respectively. The difference was statistically significant, and vitamin C was the most deficient vitamin after chemotherapy. Thus, chemotherapy may have a considerable effect on vitamin C levels in EC patients. A meta-analysis showed a negative correlation between dietary vitamin C intake and EC risk and concluded that a high level of vitamin C may prevent EC[19]. Vitamin C supplementation was found to downregulate nuclear factor kappa B activity and significantly decrease proinflammatory cytokine levels in EC patients treated with neoadjuvant radiotherapy[20].

In the current study, vitamin A and D deficiencies were found in EC patients both before and after chemotherapy, and their proportions increased following chemotherapy. However, the changes in the proportions were not statistically significant after chemotherapy. Further stratified analysis of the baseline data showed that the change in vitamin A concentration during chemotherapy might be associated with gender, while vitamin D might differ among different tumor stages. Vitamins A and D are mainly derived from food sources. EC itself can affect the intake and absorption of food, and chemotherapy drugs further damage the nutritional status of patients, resulting in more significant vitamin deficiencies in patients after treatment. In the current study, we further analyzed the difference between vitamin concentrations and BMI in EC patients before and after chemotherapy and found that vitamins A and C were significantly correlated with the change in BMI. Regression analysis of multiple vitamins and BMI revealed a statistically significant overall model for three vitamins (A, D and C). Therefore, body weight, vitamin levels and hematological indicators interact with each other during chemotherapy in EC patients, and the supplementation of macronutrients and micronutrients are equally important. Developing holistic care is the key to nutritional therapy for tumor patients.

There were different degrees of vitamin A and D deficiencies in EC patients treated with chemotherapy, and a higher proportion of vitamin A deficiency than vitamin D deficiency and no vitamin E deficiency was detected during our observation. A meta-analysis suggested that vitamin A levels were negatively correlated with EC risk[21], and further studies are needed to confirm whether it affects the prognosis of EC patients. Vitamin D has been found to inhibit tumor cell proliferation, induce cell differentiation, promote apoptosis and suppress angiogenesis[22]. A meta-analysis did not observe an association between vitamin D levels and the development of esophageal lesions[23]. Another study reported that appropriate vitamin D supplementation in postoperative EC patients improved quality of life and disease-free survival, and further multivariate analysis found that vitamin D supplementation was an independent prognostic factor for disease-free survival but was not associated with overall survival[24].

This study had some limitations: (1) the sample size was not large due to the single center retrospective design of the study; (2) a control group was not included, and it is unclear whether vitamin supplementation is beneficial in EC patients undergoing chemotherapy; (3) the results might be biased due to different disease states and chemotherapy regimens; and (4) some patients might have received targeted therapy or immunotherapy during chemotherapy, which may have had an impact on the study results. In addition, no data on response rate or overall survival were included in our analysis, and the relationship between vitamin nutritional status and prognosis in EC patients requires further investigation in multicenter prospective studies.

Vitamin deficiencies (mainly vitamins A, D, C and B₂ deficiencies) are common in EC patients during chemotherapy and may be associated with the change in BMI. In addition, chemotherapy drugs decrease hematological indicators such as hemoglobin and albumin. Appropriate nutritional interventions and vitamin supplementation can reduce the adverse effects of chemotherapy, improve overall nutritional status of patients and improve drug tolerability and quality of life.