The link between eating the different kinds of fat and pancreatitis


A team of researchers from the Mayo Clinic, the Saint Louis University School of Medicine and the Washington University School of Medicine has found evidence that suggests people eating foods with saturated fats may have fewer symptoms if they develop pancreatitis.

In their paper published in the journal Science Advances, the group describes comparing data on patients with pancreatitis and their diets.

For many years, medical scientists have been grappling with the obesity paradox in which some obese patients appear to fare better when being treated for certain conditions than non-obese patients.

In this new effort, the researchers sought to better understand why this may happen at times by focusing on pancreatitis.

Pancreatitis is inflammation of the pancreas. Prior research has shown that it can be triggered by a wide variety of events, such as having abdominal surgery or drinking too much alcohol.

Prior research has also shown that obese people are more likely to develop pancreatitis, though it is not known why. In this new effort, the researchers took a closer look at the link between pancreatitis and consumption of fat – either saturated or unsaturated.

Saturated fats are the kind of fats found in meat, butter, cheese and other foods. Unsaturated fats are found in plants and fish. Prior research has suggested people would be healthier if they reduced saturated fat consumption and ate more unsaturated fats – saturated fat has been associated with heart disease and obesity. Researchers have reported exceptions to this rule, however, which has led to the obesity paradox.

To learn more about the link between eating the different kinds of fat and pancreatitis, the researchers studied data from 20 clinical reports across 11 countries where fat consumption had been monitored for obese patients.

The researchers found that patients who ate diets heavy in saturated fats who also developed pancreatitis experienced less severe symptoms than patients who ate a diet with more unsaturated fats.

Intrigued by their findings, the team ran experiments with test mice – they fed some of them a diet heavy in saturated fats and others unsaturated fats – they then induced pancreatitis in all of them.

They found that the mice fed the saturated fats developed less severe symptoms. Taking a closer look, they found that saturated fats did not interact very well with pancreatic triglyceride lipase, which led to less production of long-chain non-esterified fatty acids – and reduced symptoms of pancreatitis.

Acute pancreatitis (AP) is an acute inflammatory process of pancreas with variable involvement of other regional tissues and remote organ systems. The diagnosis is based on two of the following three criteria: (1) Abdominal pain consistent with pancreatitis; (2) A serum amylase or lipase greater than 3 times upper normal limit; and (3) Characteristic findings from abdominal imaging[1]. The two most common etiologies of AP are gallstones (40%-70%) and alcohol (25%-35%). Other causes include medications, infectious diseases, and metabolic causes such as hypercalcemia and hypertriglyceridemia[2].

The incidence of AP varies between 4.9 and 73.4 cases per 100000 worldwide[3,4]. The overall mortality ranges from 5%-20%, depending on severity of pancreatitis. The severity of this disease is classified as mild, moderately severe, or severe, according to the 2012 revised Atlanta classification[5].

While the mortality rate is very low in mild pancreatitis (1%), there is a dramatic 30% increase in mortality in severe pancreatitis. Additionally, mortality can be up to 50% in extensive pancreatic necrosis and as high as 80% in patients with sepsis[6]. AP is associated with a hospital length of stay of about 30 d and annual health-care cost of 2.6 billion in the United States[7,8].

There are two distinctive phases of AP: (1) Early phase (within 1 wk), characterized by both local pancreatic inflammation, the systemic inflammatory response syndrome, and/or organ failure; and (2) Late phase (> 1 wk), characterized by local complications and/or persistent organ failure[2]. Hence, prevention and management of systemic inflammatory response syndrome, organ failure, and complications are imperative in order to decrease morbidity and mortality in this potentially fatal disorder.

Nowadays, there are no specific medications found to effectively treat AP, and therefore management is focused on supportive interventions such as fluid resuscitation and nutrition intervention. Nutrition management has demonstrated necessity not only in prevention and treatment of malnutrition but also in obviating systemic inflammation, reduction of complications, and therefore modifying the course of the disease[9,10].

This article aims to review the latest evidence and recommend an evidence-based practical approach to nutrition management in AP, which includes patient evaluation, nutrition management in mild, moderately severe, and severe pancreatitis, and pancreatic exocrine insufficiency (PEI) in AP.


Multiple factors are able to deteriorate nutrition status in AP, and one of the most important factors is inflammation. Inflammatory cytokines (tumor necrosis factor alpha, interleukins 1 and 6) and stress hormones (cortisol, catecholamines, and glucagon), released during pancreatitis, result in abnormal metabolism which is similar to sepsis[11].

Resting energy expenditure (REE) in patients with pancreatitis is generally higher than healthy individuals because of inflammation-induced hypermetabolism and/or septic complications. REE measured by indirect calorimetry (IC) increased in 61% of patients with AP and 82% in pancreatitis complicated by infection. m ± SD of measured REE was 111% ± 15% in mild pancreatitis, 126% ± 10% in severe pancreatitis, and 120% ± 11% in pancreatic sepsis, compared to predicted REE by Harris-Benedict equation[12]. Nutrition support may help restore energy balance and prevent malnutrition in this circumstance.

Severe inflammation leads to protein catabolism. Amino acids released from protein breakdown provide substrates for the production of acute-phase protein. This was found in 80% of patients with severe necrotizing pancreatitis[11]. Nitrogen balance can be negative up to 20-40 g/d[13,14] and patients with a negative balance had a ten-fold higher death rate than those with normal balance[15]. Muscle mass and function, measured by grip strength and respiratory muscle strength, rapidly declined within 5 d without nutrition support in healthy men suffering from AP[16].

Regarding carbohydrate metabolism, hyperglycemia is often found in patients with pancreatitis. It is a result of insulin resistance, increased glucose production from liver (gluconeogenesis), and impaired insulin secretion caused by beta-cell damage[17]. Hyperglycemia is related with pancreatic necrosis and infectious complications. As a result, blood glucose should be monitored and controlled in all patients[18].

Hypertriglyceridemia is common, and can be either a cause or a consequence of pancreatitis. Lipid catabolism and impaired lipid clearance, resulting from decreased insulin secretion, contribute to elevated serum triglycerides[18]. In the absence of gallstones and significant alcohol consumption, severe hypertriglyceridemia (serum triglycerides > 11.3 mmol/L) can be considered as a cause of AP[2,19]. Serum triglycerides level should be monitored, especially in those who receive intravenous lipid emulsions (ILEs).

Malnutrition in AP can arise from decreased oral intake as a result of anorexia, abdominal pain, vomiting, ileus, gastroparesis, gastric outlet obstruction, and inappropriate fasting for pancreatic rest[20]. In addition, pancreatic exocrine dysfunction leads to maldigestion of nutrients and may persist up to 6-18 mo after acute attack[21].

Micronutrient abnormalities are common in AP. Chronic alcohol consumption frequently leads to micronutrient deficiencies due to inadequate intake, decreased absorption, and impaired storage and utilization of nutrients. In patients with alcoholism, biochemical data demonstrate several micronutrient deficiencies including vitamin B1, B2, B3, B12, C, A, folic acid, and zinc[22,23].

Moreover, the risk of deficiencies increases in patients with severe complicated pancreatitis, requiring prolonged admission. The etiology is multifactorial including decreased intake, maldigestion, and increased demand from severe inflammation. Hypocalcemia can occur in 40%-60% of patients. The underlying causes of hypocalcemia may be related to saponification of calcium, hypomagnesemia, decreased parathyroid hormone release, and increased calcitonin levels[24,25].


Nutrients delivered to gastrointestinal tract proximal to mid-jejunum (around 40 cm distal to ligament of Trietz) stimulate pancreatic enzyme secretion. Traditional thinking was that this may lead to increased pancreatic autodigestion and worsening of pancreatitis.

As a result, the concept of “pancreatic rest” has formerly been used to guide management of AP since the 1970s. This concept states that enteral nutrition (EN) should only be started when abdominal pain has completely resolved and the pancreatic enzymes have normalized.

Based on this concept, strategies are used to minimize pancreatic stimulation such as parenteral nutrition (PN), elemental formula, and a stepwise introduction of oral diet, beginning with clear fluid. However, this concept is based on only physiologic assumption and is not supported by good scientific evidence and indeed, may result in worsening of nutritional status and poor outcomes[7,26].

Further studies have found that pancreatic enzyme secretion is significantly reduced in AP and the secretion was inversely related to the severity of pancreatitis. A lower secretion of trypsin (16-fold), amylase (22-fold), and lipase (102-fold) was found in severe pancreatitis[27]. In addition, early EN use resulted in clinically significant exacerbation of symptoms in only 4% of cases[28].

These data suggest that the injured acinar cells cannot fully respond to physiologic stimuli, and may explain why enteral feeding is safe and does not worsen autodigestion during an attack of pancreatitis.

Since the 1990s, several randomized controlled trials (RCT) and meta-analyses have demonstrated safety and benefits of enteral nutrients in terms of mortality, multiorgan failure, infection, complications, and surgical intervention[29-32]. This evidence supports the administration of EN to stimulate and maintain gut function, which is opposite to “pancreatic rest” that may give rise to gut dysfunction and worse clinical outcomes.

Enteral nutrients help maintain gut integrity, gut-associated lymphoid tissue, and gut microbiota composition. This strategy reduces bacterial, endotoxin, and pancreatic enzyme translocation, which may attenuate systemic inflammation, multiorgan failure, infection, and disease severity in AP[26,33-35]. Based on this evidence, the gastrointestinal tract should be considered as an important organ in pancreatitis patients.

Mild AP is reported in 75%-85% of all AP episodes. It is transient, self-limiting, and therefore specialized nutrition care (EN and/or PN), is not generally required[7]. Patients can consume oral diet when abdominal pain, nausea, and vomiting are improved. A full caloric, solid diet can be started safely and a stepwise introduction of oral diet, beginning with clear liquids, is unnecessary.

Randomized trials comparing a clear liquid diet and a solid diet in mild pancreatitis illustrated that initiating oral feeding with a solid diet was safe, well-tolerated, and could decrease length of hospital stay by 2 d compared with a liquid diet[40-42]. As for dietary composition, even though a low fat diet (< 30% of total energy) has been used in previous studies[40,42], this diet does not support by good scientific evidence and may lead to inadequate energy intake. Tube feeding is only recommended when oral nutrition is not feasible for more than 5 d[13]. An example of this is patients with poor oral intake resulting from persistent nausea, vomiting, and abdominal pain.

Nutrition support has been well-documented in its benefits in moderately severe and severe pancreatitis. The following aspects should be considered in this group of patients.

Nutrient requirements
Energy requirement should be estimated with IC if possible, or 25 kcal/kg/d may be used as energy goal. Many non-static variables affect energy expenditure in severe pancreatitis, such as body temperature, volume status, and medications. These variables result in the poor accuracy of predictive equations. IC is the goal standard to determine energy expenditure, and thus IC measurement may help prevent over- or underfeeding.

Energy requirement, whether by calorimetry or predictive equation, should be reevaluated more than once per week in order to reach appropriate energy balance. Estimated protein requirements are higher than healthy individuals (1.2-1.5 g/kg/d). This may improve nitrogen balance and is related to a decrease in 28-d mortality in critically ill patients[43]. Mixed source of energy from carbohydrate, fat, and protein should be provided[20,44].

A daily dose of multivitamins and trace elements is recommended especially in patients receiving total PN[44]. Micronutrients should be supplemented in patients with confirmed or suspected deficiencies.

Route of nutrition support
EN: Enteral feeding should be considered as a preferred route of nutrition support[2,13,45]. A 2018 meta-analysis of 5 RCTs (348 patients) demonstrated that EN, when compared to PN, was associated with a significant reduction in death with risk ratio (RR) of 0.36 (95%CI: 0.20-0.65) and multiple organ failure with RR of 0.39 (95%CI: 0.21-0.73)[31]. These benefits were confirmed in a recent meta-analysis of 11 studies including 562 patients. The results showed that EN significantly decreased mortality rate (RR = 0.43; 95%CI: 0.23-0.78), the risk of complications (RR = 0.53; 95%CI: 0.39-0.71), and mean length of hospital stay (mean difference = -2.93, 95%CI: -4.52 to -1.34)[32]. Local complications (necrosis, fistulas, ascites, and pseudocyst) are not contraindications for enteral feeding[13].

EN should be started after adequate resuscitation and stable hemodynamic status. Many studies have shown advantages of early enteral feeding in severe pancreatitis. Meta-analyses illustrated that early EN within 48 h of admission was associated with significant reductions in mortality, infectious complications, multi-organ failure, surgical intervention, and length of hospitalization[46,47].

In contrast, early EN may not be better than on-demand oral diet at 72 h. A multicenter RCT in 205 patients compared early EN within 24 h vs on-demand oral diet 72 h, with tube feeding provided at day 4 if the oral diet was not tolerated. There was no significant difference between two groups in the rate of major infection or death, and tube feeding could be prevented in 69% of patients in on-demand group[48].

Over 80% of the patients in this study were admitted to medical ward and only 18% required intensive care unit (ICU) admission, which indicates that most of them may actually have moderately severe pancreatitis. This result suggests that, in non-ICU patients, on-demand oral diet may be tried for 3 d and tube feeding should be initiated at day 4 if the oral diet is unsuccessful. However, more data are required before a recommendation can be made about this issue.

In patients who need tube feeding, continuous feeding is recommended over bolus feeding by current guidelines[2,13]. Better feeding tolerance and fewer interruptions of EN delivery due to elevated residuals and vomiting were found in continuous infusion compared with bolus group[49,50].

Given that pancreatic enzymes stimulated by enteral nutrients may lead to pancreatic autodigestion, the role of antisecretory agents, including somatostatin and its analogues (octreotide), has been investigated in several studies. However, the result remains inconclusive. A RCT and recent Cochrane review revealed no benefit among treatment group with respect to mortality, complications, and duration of pain[51,52]. This may be due to a dramatic decrease in pancreatic secretion during AP.

Gastric vs small bowel feeding: Traditionally, it is believed that small bowel feeding was associated with less pancreatic stimulation and autodigestion. Nevertheless, a meta-analysis found that nasogastric feeding was not inferior to nasojejunal feeding in terms of exacerbation of pain (RR = 0.94; 95%CI: 0.32-2.70), aspiration (RR = 0.46; 95%CI: 0.14-1.53), meeting energy balance (RR = 1.00; 95%CI: 0.92-1.09), and mortality (RR = 0.69; 95%CI: 0.37-1.29)[53].

This is predicated by lack of impact on pancreatic secretion regardless of feeding route during AP. Initiating EN in the stomach is technically easier, cheaper, and may reduce the time to start EN while small bowel feeding generally requires special technique and takes more time for tube placement. For these reasons, nasogastric tube may be used as a first line therapy in order to achieve benefits of early EN in patients with severe pancreatitis.

Jejunal feeding should be considered in patients who cannot tolerate gastric feeding. It may be necessary in those with severe gastroparesis or partial gastric outlet obstruction either from pancreatic edema or pseudocysts[54]. An intraoperative jejunostomy tube may be placed for postoperative feeding in patients undergoing surgery from other indications[13].

Polymeric vs elemental/semi-elemental formulas: Elemental and semi-elemental formulas are thought to induce less pancreatic stimulation, require less digestion, and are readily absorbed into small intestine. A physiological study in healthy subjects found that pancreatic enzyme secretion reduced by 50% when polymeric formula was changed to elemental formula[55]. Thus, semi-elemental and elemental formulas have been used in many studies on AP.

Even though few studies directly compare between elemental/semi-elemental formulas and polymeric formula, there are one RCT and one retrospective cohort study showing elemental and semi-elemental formulas were not superior over polymeric formula in terms of feeding tolerance, diarrhea, and infectious complications[56,57]. Additionally, a meta-analysis of 10 RCTs using indirect adjusted method illustrated that the use of semi-elemental or elemental formula did not result in a significant difference in feeding intolerance (RR = 0.62; 95%CI: 0.10-3.97), infection (RR = 0.48; 95%CI: 0.06-3.76), and death (RR = 0.63; 95%CI: 0.04-9.86)[58]. Furthermore, the weekly cost for semi-elemental formula is 7-fold higher than polymeric formula[7]. Hence, the use of polymeric formula may be effective and practical in severe pancreatitis.

PN: PN is indicated when patients cannot tolerate EN. Some patients develop intestinal failure type I or II from systemic or local complications such as severe ileus and duodenal obstruction from pancreatic edema or pseudocyst. When PN is required, a mixed fuel solution (carbohydrate, protein, and lipids) is recommended. Glucose should not be more than the maximal level of glucose oxidation (4-7 mg/kg/min or 5-6 g/kg/d), and a target blood glucose range of 7.7-10 mmol/L is recommended[59,60]. ILEs can be safely started and the recommended dose is 0.8-1.5 g/kg/d[20,44].

ILEs dose may need to be reduced or discontinued if serum triglyceride concentrations greater than 4.5 mmol/L[18,61]. PN initiation may need to be delayed until after 5-7 d of admission[20,59]. Because initiating PN at this point may be associated with better outcomes, including decreased mortality, overall complication, and length of hospitalization[62]. Further studies are needed to confirm appropriate time and clinical benefits of PN in AP with intestinal failure. The recommended route of nutrition support is summarized in Figure ​Figure11.

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Figure 1
Route of nutrition treatment in acute pancreatitis. ICU: Intensive care unit; NG: Nasogastric tube; NJ: Nasojejunal tube.

Role of nutritional supplements
Glutamine: Glutamine is considered a conditionally essential amino acid with antioxidative effects that improves immune function and intestinal integrity. Its depletion has been demonstrated in critically ill patients because of the increased demand during metabolic stress[63]. Glutamine supplementation may play a role in critical illnesses, including severe pancreatitis[10].

A meta-analysis of 12 RCTs demonstrated that glutamine was associated with lower infectious complications (RR = 0.58; 95%CI: 0.39-0.87) and mortality (RR = 0.30; 95%CI: 0.15-0.60). In this study, only patients receiving total PN but not EN showed statistically significant benefits[64].

Another meta-analysis confirmed these findings and, again, intravenous glutamine was related with more advantages[65]. A recent RCT of enteral glutamine showed improvement in organ failure score without significant benefits in infected necrosis and mortality[66]. Overall, intravenous glutamine seems to give benefits in patients with total PN while the beneficial effects of enteral glutamine needs to be investigated in the future. The recommended dose of glutamine supplementation is between 0.3-0.5 g/kg/d.

Probiotics: Intestinal barrier dysfunction may induce bacterial translocation and infected necrosis, being the major cause of morbidity and mortality in severe pancreatitis. Probiotics may help improve gut integrity and immune function, and thus prevent bacterial translocation[67,68]. Lactobacillus plantarum decreased intestinal permeability, infectious complications, systemic inflammation, and multiorgan failure, but did not improve mortality rate in small RCTs[69-71].

In contrast, a multispecies probiotic preparation did not reduce infection and was associated with an increased mortality (RR = 2.53; 95%CI: 1.22-5.25)[72]. These data suggest the potential benefits of single strain probiotic (Lactobacillus plantarum) in severe pancreatitis; however, further validated studies are needed before its advantages could be confirmed.

Omega-3 fatty acids: Omega-3 fatty acids have shown beneficial anti-inflammatory effects and may improve systemic inflammation, multiorgan failure, and clinical outcomes in severe pancreatitis. A meta-analysis of 8 small RCTs demonstrated that the administration of omega-3 fatty acids was beneficial for reducing mortality, infectious complications, and length of hospital stay, especially when received parenterally. Nonetheless, large and rigorously designed RCTs are required to elucidate the efficacy of omega-3 fatty acid supplement in severe pancreatitis[73].

Antioxidants: Antioxidants (vitamin A, vitamin C, vitamin E, selenium, and N-acetyl cysteine) may reduce inflammation and improve outcomes in severe pancreatitis. Nevertheless, few small studies with varied dose and duration of antioxidants leaded to mixed outcomes[10]. Larger and well-designed clinical trials are needed to confirm potential benefits of antioxidants in this disorder.

reference link :

More information: Biswajit Khatua et al. Adipose saturation reduces lipotoxic systemic inflammation and explains the obesity paradox, Science Advances (2021). DOI: 10.1126/sciadv.abd6449


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