Deficiency of fat-soluble vitamins in chronic pancreatitis: A systematic review and meta-analysis

doi:10.1016/j.pan.2016.09.008

Pancreatology

Volume 16, Issue 6, November–December 2016, Pages 988-994

https://doi.org/10.1016/j.pan.2016.09.008 Get rights and content

Abstract

Background and aims

Chronic pancreatitis (CP) patients are at risk for fat-soluble vitamins (A, D, E, K) deficiency, but available studies are small and heterogeneous. We conducted a systematic review and meta-analysis to determine the prevalence of fat–soluble vitamins deficiency in CP patients.

Methods

Medline was searched up to January 2016 for case series and case-control studies reporting prevalence of fat-soluble vitamin deficiency in CP patients. The prevalent deficiency rate was pooled for included studies, and deficiency rate between CP and controls, with relative odds ratio (OR) and 95% confidence interval (CI) calculated for case-control studies.

Results

Twelve studies including 548 patients included. With a random-effect model, the pooled prevalence rate of vitamin A, D and E deficiency were 16.8% (95%CI 6.9–35.7), 57.6% (95%CI 43.9–70.4) and 29.2% (95%CI 8.6–64.5) respectively, with considerable heterogeneity (I² = 75%, 87.1% and 92%). Only one study evaluated vitamin K deficiency. The pooled OR for vitamin D deficiency in CP cases compared with controls was 1.17 (95% CI 0.77–1.78). Sensitivity analyses showed lower prevalence of vitamin A and E, and higher prevalence of vitamin D deficiency in high-quality studies. The rate of pancreatic exocrine insufficiency did not seem affect the deficiency rates, while the use of different cut-offs influences results and heterogeneity for vitamin E, but not A.

Conclusions

Fat-soluble vitamins deficiency is frequent in CP patients, with considerable heterogeneity. There is, however, no apparent increased risk of vitamin D deficiency in CP compared to controls. Larger, high-quality studies are necessary to better estimate the prevalence of fat-soluble vitamins deficiency, including vitamin K.

Section snippets

Background

Chronic pancreatitis (CP) is the most important and common etiology of pancreatic exocrine insufficiency (PEI), causing steatorrhea, meteorism, abdominal pain and malnutrition. During the course of the disease, pancreatic enzyme production decreases, resulting in maldigestion and leading to deficiencies of macro- and micronutrients. Pain, diabetes and alcoholism can also interfere with proper nutrition in patients with CP [1], [2]. Several nutritional deficiencies have been demonstrated in

Search strategy and study selection

A computerized literature search of MEDLINE and of the Cochrane database did not identify any prior systematic review on CP and fat-soluble vitamin deficiencies. In our search for original studies, we performed a MEDLINE search (until January 2016). Specific search terms were: (Vitamin A OR 11-cis-Retinol OR 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol, (all-E)-Isomer OR All-Trans-Retinol OR Aquasol A OR Retinol OR vitamin A1 OR vitamin D OR cholecalciferol OR

Results

Three-hundred-eighty-one potential studies where identified throughout an initial search, of which 357 were excluded, as they were not related to the study topic or did not fulfill the inclusion criteria. Twenty-four studies met the inclusion criteria and were considered for the analysis, of which 12 were excluded, because these did not report the prevalence of deficiency of the vitamins of interest. Finally, 12 studies remained for qualitative analysis and quantitative synthesis (Fig. 1).

Discussion

Previous studies have reported that patients suffering from CP are at risk of developing fat-soluble vitamins deficiency. However, available studies are often heterogeneous and conducted on relatively small series of patients. This is the first systematic review and meta-analysis on this topic, highlighting the pooled prevalence of fat-soluble vitamin deficiencies in CP patients.

Twelve articles were reviewed, and in spite of a considerable heterogeneity for all analyses, the prevalence rate of

Conflicts of interest

The authors disclose no conflicts.

Authors contribution

G.C. and P.S. contributed with study concept and design, analysis and interpretation of data, statistical analysis, and drafting of the manuscript; E.M., S.S., A.H., A.K., M.M. and A.W. contributed with acquisition of data, analysis and interpretation of data, drafting of the manuscript; P.M with analysis and interpretation of data; all authors performed critical revision of the manuscript for important intellectual content.

References (39)

B. Lindkvist et al.
Clinical, anthropometric and laboratory nutritional markers of pancreatic exocrine insufficiency: prevalence and diagnostic use
Pancreatology
(2015)
S.T. Mann et al.
Alterations of bone mineral density and bone metabolism in patients with various grades of chronic pancreatitis
Metabolism
(2003)
Y. Twersky et al.
Nutritional deficiencies in chronic pancreatitis
Gastroenterol Clin North Am
(1989)
S.N. Duggan et al.
High prevalence of osteoporosis in patients with chronic pancreatitis: a systematic review and meta-analysis
Clin Gastroenterol Hepatol
(2014)
M.S. Hamidi et al.
Vitamin K and bone health
J Clin Densitom
(2013)
A. Sommer
Vitamin a deficiency and clinical disease: an historical overview
J Nutr
(2008)
V. Kunadian et al.
Vitamin D deficiency and coronary artery disease: a review of the evidence
Am Heart J
(2014)
D. Moher et al.
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement
J Clin Epidemiol
(2009)
R. DerSimonian et al.
Meta-analysis in clinical trials
Control Clin Tr
(1986)
E.C. Sikkens et al.
The prevalence of fat-soluble vitamin deficiencies and a decreased bone mass in patients with chronic pancreatitis
Pancreatology
(2013)

H. Dujsikova et al.

Occurrence of metabolic osteopathy in patients with chronic pancreatitis

Pancreatology

(2008)

B. Gao et al.

Alcoholic liver disease: pathogenesis and new therapeutic targets

Gastroenterology

(2011)

Maret G. Traber

Vitamin E inadequacy in humans: causes and consequences

Adv Nutr Int Rev J

(2014)

S.A. Hoogenboom et al.

Systematic review and meta-analysis on the prevalence of vitamin D deficiency in patients with chronic pancreatitis

Pancreatology

(2016)

F. Remy et al.

Lubos Sobotka. Basics in Clinical Nutrition: nutritional support in acute and chronic pancreatitis. e-SPEN

Eur e J Clin Nutr Metab

(2010)

I. Kalvaria et al.

Biochemical vitamin E deficiency in chronic pancreatitis

Int J Pancreatol

(1986)

M.B. Sobral-Oliveira et al.

Nutritional profile of asymptomatic alcoholic patients

Arq Gastroenterol

(2011)

S.H. Je et al.

Vitamin K supplement along with vitamin D and calcium reduced serum concentration of undercarboxylated osteocalcin while increasing bone mineral density in Korean postmenopausal women over sixty-years-old

J Korean Med Sci

(2011)

S.B. Carr et al.

The role of vitamins in cystic fibrosis

J R Soc Med

(2000)

Cited by (70)

Determination of vitamins K1, K2, B6, and D3 using reduced graphene oxide fabricated using a bismuth nanoparticle embedded polypyrrole nanocomposite based optical sensor
2024, Materials Advances
This research reports a simple and selective detection of vitamins K1, K2, B6, and D3 in human blood (serum/plasma) using reduced graphene oxide fabricated using the bismuth nanoparticle embedded polypyrrole nanocomposite (rGO/pPy/Bi NC) as an optical sensing material. The nanocomposite was thoroughly characterized for its functional properties using FTIR and for its morphology using SEM, AFM and TEM. The phase purity of the nanocomposite was studied using XRD diffractometry. SEM, TEM, and AFM studies confirmed the presence of nanoparticles on the polypyrrole covered sheets of rGO. The average crystallite size of GO and rGO/pPY/Bi NC was calculated using three methods using XRD analysis data. The selectivity of rGO/pPy/Bi NC is based on quenching of the optical band produced by the nanocomposite when it comes in contact with the respective vitamin in the corresponding medium. The limits of detection of vitamins K1, K2, B6, and D3 using rGO/pPY/Bi NC were found to be 0.075 ng mL⁻¹, 0.1 ng mL⁻¹, 0.12 ng mL⁻¹, and 0.15 ng mL⁻¹, respectively. However, the limits of quantification were found to be 0.29 ng mL⁻¹, 0.3 ng mL⁻¹, 0.38 ng mL⁻¹, and 0.48 ng mL⁻¹ for vitamins K1, K2, B6, and D3, respectively. The detection of vitamins in human blood (serum/plasma) with rGO/pPY/Bi NC is attributed to the novelty, simplicity, and cost-effectiveness of the sensing material. The pH sensitive rGO/pPy/Bi NC is capable of sensing four different vitamins due to the synergistic effect of rGO, Bi NPs and polypyrrole.
AGA Clinical Practice Update on the Epidemiology, Evaluation, and Management of Exocrine Pancreatic Insufficiency: Expert Review
2023, Gastroenterology
Exocrine pancreatic insufficiency (EPI) is a disorder caused by the failure of the pancreas to deliver a minimum/threshold level of specific pancreatic digestive enzymes to the intestine, leading to the maldigestion of nutrients and macronutrients, resulting in their variable deficiencies. EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately. There is an urgent need to increase awareness of and treatment for this condition. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to provide Best Practice Advice on the epidemiology, evaluation, and management of EPI.
This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations.
Best Practice Advice Statements
EPI should be suspected in patients with high-risk clinical conditions, such as chronic pancreatitis, relapsing acute pancreatitis, pancreatic ductal adenocarcinoma, cystic fibrosis, and previous pancreatic surgery.
EPI should be considered in patients with moderate-risk clinical conditions, such as duodenal diseases, including celiac and Crohn's disease; previous intestinal surgery; longstanding diabetes mellitus; and hypersecretory states (eg, Zollinger–Ellison syndrome).
Clinical features of EPI include steatorrhea with or without diarrhea, weight loss, bloating, excessive flatulence, fat-soluble vitamin deficiencies, and protein-calorie malnutrition.
Fecal elastase test is the most appropriate initial test and must be performed on a semi-solid or solid stool specimen. A fecal elastase level <100 μg/g of stool provides good evidence of EPI, and levels of 100–200 μg/g are indeterminate for EPI.
Fecal elastase testing can be performed while on pancreatic enzyme replacement therapy.
Fecal fat testing is rarely needed and must be performed when on a high-fat diet. Quantitative testing is generally not practical for routine clinical use.
Response to a therapeutic trial of pancreatic enzymes is unreliable for EPI diagnosis.
Cross-sectional imaging methods (computed tomography scan, magnetic resonance imaging, and endoscopic ultrasound) cannot identify EPI, although they play an important role in the diagnosis of benign and malignant pancreatic disease.
Breath tests and direct pancreatic function tests hold promise, but are not widely available in the United States.
Once EPI is diagnosed, treatment with pancreatic enzyme replacement therapy (PERT) is required. If EPI is left untreated, it will result in complications related to fat malabsorption and malnutrition, having a negative impact on quality of life.
PERT formulations are all derived from porcine sources and are equally effective at equivalent doses. There is a need for H2 or proton pump inhibitor therapy with non–enteric-coated preparations.
PERT should be taken during the meal, with the initial treatment of at least 40,000 USP units of lipase during each meal in adults and one-half of that with snacks. The subsequent dosage can be adjusted based on the meal size and fat content.
Routine supplementation and monitoring of fat-soluble vitamin levels are appropriate. Dietary modifications include a low-moderate fat diet with frequent smaller meals and avoiding very-low-fat diets.
Measures of successful treatment with PERT include reduction in steatorrhea and associated gastrointestinal symptoms; a gain of weight, muscle mass, and muscle function; and improvement in fat-soluble vitamin levels.
EPI should be monitored and baseline measurements of nutritional status should be obtained (body mass index, quality-of-life measure, and fat-soluble vitamin levels). A baseline dual-energy x-ray absorptiometry scan should be obtained and repeated every 1–2 years.
Autoimmune pancreatitis and micronutrients
2023, Digestive and Liver Disease
Nutritional deficiencies, including fat-soluble vitamins and minerals have been detected in many autoimmune diseases, including those involving the digestive system, but have yet to be assessed in autoimmune pancreatitis (AIP). The aim of the present study was to determine the prevalence of micronutrient deficiencies in patients with AIP as well as to investigate their relationship with relapse.
We retrospectively analysed medical records of patients treated for AIP. Demographic and clinical data were collected.
One hundred patients were included in the final analysis. The male-to-female ratio was 2.5:1; median age at diagnosis was 57 years (range 19–85). Median follow-up was 53 months, and during this time, 38% of patients suffered from at least one micronutrient deficiency. The most prevalent micronutrient deficiencies were vitamin D (16.1%) and zinc (25.5%). Relapse was observed in 37% of the AIP patients. Initial analysis showed that AIP relapse was associated with any micronutrient deficiency as well as zinc and vitamin D deficiency, but after stratifying for AIP type 1 and adjusting for PEI and elevated IgG4 levels, the association ceased to be statistically significant.
Zinc and vitamin D deficiencies may be common in patients with AIP, indicating that these micronutrients might play a role in the natural course of AIP. Importantly, any micronutrient deficiency may be prevalent even in the light of treated PEI, which emphasizes the potential of micronutrients as an additional tool in the workup and follow-up of AIP patients.
Fat-soluble vitamin and phytochemical metabolites: Production, gastrointestinal absorption, and health effects
2023, Progress in Lipid Research
Consumption of diets rich in fruits and vegetables, which provide some fat-soluble vitamins and many phytochemicals, is associated with a lower risk of developing certain degenerative diseases. It is well accepted that not only the parent compounds, but also their derivatives formed upon enzymatic or nonenzymatic transformations, can produce protective biological effects. These derivatives can be formed during food storage, processing, or cooking. They can also be formed in the lumen of the upper digestive tract during digestion, or via metabolism by microbiota in the colon. This review compiles the known metabolites of fat-soluble vitamins and fat-soluble phytochemicals (FSV and FSP) that have been identified in food and in the human digestive tract, or could potentially be present based on the known reactivity of the parent compounds in normal or pathological conditions, or following surgical interventions of the digestive tract or consumption of xenobiotics known to impair lipid absorption. It also covers the very limited data available on the bioavailability (absorption, intestinal mucosa metabolism) and summarizes their effects on health. Notably, despite great interest in identifying bioactive derivatives of FSV and FSP, studying their absorption, and probing their putative health effects, much research remains to be conducted to understand and capitalize on the potential of these molecules to preserve health.
Progressive reduction in circulating levels of carotenoids and other micronutrients in patients with chronic pancreatitis
2022, Pancreatology
Citation Excerpt :
More importantly, some of these differences were not only significant but also have a large effect size. Our observation of significantly lower levels of selected carotenoids, α-tocopherol, and vitamin D in CP patients than in controls was in agreement with the findings of most previous studies [19–27]. However, the present study has contributed to an improved understanding of important roles of carotenoid and vitamin status in the etiology and progression of CP for several reasons.
Although micronutrients modulate immunity and inflammation, it remains elusive whether they are implicated in the development and progression of chronic pancreatitis (CP). This study aimed to investigate differences in the circulating levels of selected carotenoids and vitamins between CP and controls and trends in the levels of these micronutrients across controls, early CP, and definite CP.
Demographic and lifestyle data were extracted from medical records for 53 patients with CP (13 early and 38 definite) and obtained using a questionnaire for 52 controls. Plasma β-carotene, lycopene, cryptoxanthin, zeaxanthin, and α-tocopherol and serum 25(OH)D, folate, IL-6, TNF-α, and MCP-1 were measured with state-of-the-art methods.
The levels of all micronutrients (except folate) were significantly lower in CP than in controls. There was a progressive decrease in the levels of these micronutrients across controls, early CP, and definite CP (all p values for trend: ≤0.0012); e.g., plasma lycopene was 36.6, 21.5, and 14.5 μg/dL for controls, early CP, and definite CP, respectively. After adjustment for confounders, there were strong, inverse associations between the levels of all micronutrients (except folate) and CP (e.g., OR (95% CI) for ≥ median vs. <median: 0.10 (0.04, 0.27) for lycopene, 0.15 (0.05, 0.38) for α-tocopherol, and 0.24 (0.09, 0.64) for 25(OH)D). These associations became weaker after additional adjustment for inflammation markers (IL-6, TNF-α, and MCP-1).
The circulating levels of some carotenoids, α-tocopherol, and vitamin D were reduced in CP patients compared with controls and this reduction was more pronounced in definite CP than in early CP.
Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: An international expert survey and case vignette study
2022, Pancreatology
Citation Excerpt :
Deficiencies of fat-soluble vitamins A, D, E and K are frequently demonstrated in patients with EPI and should therefore be part of the standard diagnostic work-up for EPI [5,32,34]. In a meta-analysis of twelve studies including 548 patients with CP, the pooled prevalence rates for vitamin A, D and E deficiency were reported 16.8% (95% CI 6.9–35.7), 57.6% (95% CI 43.9–70.4) and 29.2% (95% CI 8.6–64.5) respectively [34]. Levels of magnesium, pre-albumin and retinol-binding protein below normal values and a HbA1c level above the upper limit are less frequent but are associated with EPI as well [7,33,35].
Despite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency.
An online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years.
Overall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency.
This survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.

View all citing articles on Scopus

^☆: The paper is part of the P-BONE study group project, supported by the Pancreas 2000 educational project.

View full text

Original ArticleDeficiency of fat-soluble vitamins in chronic pancreatitis: A systematic review and meta-analysis☆

Abstract

Background and aims

Methods

Results

Conclusions

Section snippets

Background

Search strategy and study selection

Results

Discussion

Conflicts of interest

Authors contribution

Pancreatology

Metabolism

Gastroenterol Clin North Am

Clin Gastroenterol Hepatol

J Clin Densitom

J Nutr

Am Heart J

J Clin Epidemiol

Control Clin Tr

Pancreatology

Pancreatology

Gastroenterology

Adv Nutr Int Rev J

Pancreatology

Lubos Sobotka. Basics in Clinical Nutrition: nutritional support in acute and chronic pancreatitis. e-SPEN

Eur e J Clin Nutr Metab

Biochemical vitamin E deficiency in chronic pancreatitis

Int J Pancreatol

Nutritional profile of asymptomatic alcoholic patients

Arq Gastroenterol

Vitamin K supplement along with vitamin D and calcium reduced serum concentration of undercarboxylated osteocalcin while increasing bone mineral density in Korean postmenopausal women over sixty-years-old

J Korean Med Sci

The role of vitamins in cystic fibrosis

J R Soc Med

Original Article
Deficiency of fat-soluble vitamins in chronic pancreatitis: A systematic review and meta-analysis☆