Reviews of pancreatitis (whether acute bouts or chronic disease) often refer to high fat diets as a predisposing factor, and suggest that the treatment regimen should include feeding a low-fat diet. Discussion in clinical practice had suggested that high fat diets lead to persistent hyperlipidaemia (whether high cholesterol, lipids or triglycerides), that predispose to pancreatitis. Many texts refer to hyperlipidaemia as a predisposition to the clinical signs associated with pancreatitis, but examination of many of these texts indicates they have been misquoted, with hyperlipidaemia not being a proven predisposing factor. In two commonly cited research papers, Haig (1970) and Yago et al (1997), for example, high fat diets were fed and there was an association with an increase in pancreatic secretion and the enzymes within the secretions, but no correlation with clinical signs.
Is feeding a high fat diet a predisposing factor to pancreatitis in dogs?
In first opinion veterinary practice veterinary professionals are often told not to feed high fat diets to dogs with, or predisposed to, pancreatitis. This includes those with hyperlipidaemia, even without clinical signs of pancreatitis, as feeding high fats diets can induce bouts of acute pancreatitis.
This review of the literature aimed to find and then evaluate any links between high fat diets and pancreatitis; and to investigate any published case reports or research surrounding this subject.
Predisposing factors to pancreatitis
Pancreatitis is a very common disease in both dogs and cats, with the potential for very serious consequences (Watson, 2015). The clinical picture of dogs and cats with pancreatitis varies greatly (from very mild to severe or even fatal) (Xenoulis, 2015), which highlights the importance of removing avoidable risk factors.
Many of the predisposing factors are potentially cause and effect and there have been proven links between many of them: obesity and breed; obesity and neutering; hyperlipidaemia (including hypertriglyceridaemia) and obesity (German, 2011). Breed, neuter status and age are all risk factors that cannot be altered, but body condition score (overweight or obese) and diet can be controlled.
Breed disposition
Predisposing factors to chronic pancreatitis include a breed disposition for Cocker Spaniels, Cavalier King Charles Spaniels, Border Collies and Boxers in a UK-based study (Figure 1) (Watson et al, 2007). The same study suggested that Cocker Spaniels had an increased relative risk for both acute and chronic pancreatitis combined. Research into English Cocker Spaniels suggests it is part of a polysystemic immune-mediated disease in this breed (Watson, 2012). The histological and clinical appearance is different in different breeds, suggesting that aetiologies may also be different. Overweight and obesity increase incidence rates (Lem et al, 2008), as does neutering (Hess et al, 1999), and hyperlipidaemia (Xenoulis and Steiner, 2010).
Medications
Certain medications such as phenobarbitone in combination with potassium bromide (Gaskill and Cribb, 2000), azathioprine (though a very small scale study with concurrent use of prednisolone) (Moriello et al, 1987), and many more beyond the scope of this literature review, have all shown to increase risk for pancreatitis.
Calcium levels
There is emerging work investigating serum calcium levels in acute pancreatitis cases. Such cases have been shown to have decreased 25-(OH) D levels compared with healthy individuals, which the authors postulated might be associated with calcium imbalances and mortality rate in canine acute pancreatitis (Kim et al, 2017). There were limitations to this study (number in the study, no histological evaluation of the pancreas), but as a pilot study it showed that there are some very interesting areas for future study; for example it suggested there were associated alterations in C-reactive protein (CRP), a marker of inflammation, with the vitamin D and calcium imbalances, and highlighted the possibility of monitoring these as potential risk factors (Kim et al, 2017). With vitamin D being a fat-soluble vitamin there is also a postulated link between fat content and vitamin levels (Kim et al, 2017).
Chylomicrons
The exact mechanism of inducing acute pancreatitis is unclear, but is thought to be due to increased levels of chylomicrons in the blood stream. Chylomicrons are lipoprotein particles that consist of triglycerides (85–92%), phospholipids (6–12%), cholesterol (1–3%), and proteins (1–2%). They transport lipids from the intestine to other sites for use as an energy source. Chylomicrons are usually formed 1–3 hours post-prandially and cleared within 8 hours. However, when triglyceride levels exceed 1000 mg/dl, chylomicrons are almost always present. These low-density particles are very large and may obstruct capillaries leading to local ischaemia and acidaemia. The degradation of triglycerides, by pancreatic lipase, to free fatty acids can lead to cytotoxic injury resulting in further local injury that causes a positive feedback to increase inflammatory mediators and free radicals, thus instigating pancreatitis (Frenkel, 2007).
Lipid metabolism
Canines exhibit unique characteristics in lipid metabolism allowing hyperlipidaemia to be subdivided into two categories based on whether irregularities are occurring in exogenous (lipid rich diets) and/or endogenous lipid metabolism pathways (Mori et al, 2009). Incidence rates of hyperlipidaemia in canines are not often quoted, just stated as being common (Xenoulis, 2015; DeMarco et al, 2017; Xenoulis and Steiner, 2015). Incidence rates in asymptomatic Schnauzers and Shetland Sheepdogs suggested that the frequency of primary hyperlipidaemia was between 32.8% and 56.4%, (DeMarco et al, 2017). The pathogenesis of hypertriglyceridaemia-induced pancreatitis is poorly understood (Watson, 2015). It is postulated that pancreatic lipase might break down triglycerides to fatty acids within the pancreas resulting in acinar damage (Tsuang et al, 2009). The pancreatic acinar cell is the functional unit of the exocrine pancreas. It synthesises, stores, and secretes digestive enzymes. Inappropriate early activation of trypsin within the acinar cells activates other zymogens and causes autodigestion and severe inflammation (Watson, 2015). An alternative theory in the same paper, suggested that hyperviscosity (due to increased lipid content) of the blood can compromise pancreatic oxygen supply (Tsuang et al, 2009).
Nutrition
Watson et al (2010) investigated various clinical parameters of 61 dogs presented to a veterinary teaching hospital between 2002 and 2006. The published report of the work noted that the dogs had a perceived reduction of abdominal pain when fed a low-fat diet; though there was no quantitative measurement of pain scores in these animals, and no control diet. The study does not state the nutrient composition of the food and the type of fat that the diet contained. In this study all of the cases were naturally occurring rather than induced pancreatitis, with multiple different breeds and crossbreeds. No statistical analysis was conducted as there was no control group; specificity and positive and negative predictive values also could not be calculated. There was discussion in the paper that obese dogs (body condition score 5/5) had a higher predisposition for pancreatitis; there was no discussion, however, regarding what these dogs were being fed or whether the dogs with the higher body condition scores (BCS) had a higher rate of hyperlipidaemia.
Lem et al (2008) specifically looked at dietary factors and links with pancreatitis. Various continuous data (age, weight, hospitalisation time, number of days receiving fluids intravenously, and serum cPLI were statistically analysed. It should be noted that the control dogs were those diagnosed with renal failure, as the number of animals that were presented to the hospital with renal disease was similar to that of being diagnosed with pancreatitis. Statistical analysis for the dietary factors were summarised as frequencies and compared between the case and control groups by use of χ2 or Fisher's exact test. Based on information extracted from the clinical history, ingesting an unusual food item (OR, 4.3) increased the odds of pancreatitis compared with the control group, so those that ate an unusual food item were 4.3 times more likely to develop pancreatitis than those that did not.
Based on information gathered through a telephone questionnaire, ingesting unusual food items (OR, 6.1), ingesting table scraps the week before diagnosis (OR, 2.2) or throughout life (OR, 2.2), and getting into the dustbin/rubbish (OR, 13.2) increased the odds of pancreatitis, compared with the control group. Multivariable modelling indicated that reporting exposure to ≥1 dietary factor during the telephone questionnaire (OR, 2.6), being overweight (OR, 1.3) or neutered (OR, 3.6), previous surgery other than neutering (OR, 21.1), and the interaction between neuter status and previous surgery other than neutering (OR, 0.1) were associated with the odds of pancreatitis.
The breeds of the dogs within the study were not described, but there were comments in the discussion that there was no association between sporting breeds and miniature Poodles (Lem et al, 2008).
The paper did discuss limitations of the study using a control group with renal disease. The diet consumed by the control group was not revealed. It should be noted that renal diets have a higher fat content copared with lifestage diets. Animals suffering from renal compromise are often dysorexic, in some cases this can lead to anorexia, so owners often feed high fat treats and table scraps. This could therefore falsely decrease the measure of association between certain dietary factors and pancreatitis, hence making it more difficult to identify a significant relationship in the statistical analysis.
James et al (2009) studied various enzymes associated with pancreatic response to the fat content of different diets. Ten healthy staff-owned dogs were used for the study, and inclusion onto the study required no history of any pancreatic or gastrointestinal disturbances. The results were analysed using a repeated-measure general ANOVA, with a significance set at a value of p≤0.05. Results of this study showed no significant effect of the content of fat or the presence or absence of supplemental pancreatic enzymes and medium chained triglycerides (MCTs) on the degree of pancreatic stimulation (assessed by measurement of serum canine trypsin-like immunoreactivity (cTLI), canine pancreatic lipase immunoreactivity (cPLI), and gastrin concentrations) in healthy dogs. There were some differences in the diets, but not a significant difference (p=0.33). In all the diets the MCT content, not type, was investigated; differences in fat type would be of interest in their pancreatic response. Pancreatic response in unhealthy animals could have the potential to be different, and would prove to be of interest for further investigation. These results were similar to Czako et al (2007), and found that the fat content of the diet only played a role in severe (necrotising) pancreatitis cases. The study demonstrated that the high-cholesterol diet did not damage the exocrine pancreas, and did not alter the course of acute oedematous pancreatitis, but it did aggravate acute necrotising pancreatitis. In healthy rats in the Czako et al (2007) study there was no change in outcome when fed different diets.
There are large ethical implications to take into consideration when investigating any treatment intervention for a disease process that is potentially life threatening and notoriously painful. The retrospective study of Watson et al (2010) and Lem et al (2008) looked at the clinical and dietary history of dogs with pancreatitis, so there is no issue with a control pancreatitis group that did not receive treatment. James et al's (2009) study looked at healthy individuals, so there were no ethical issues with a control group not receiving pain medication or other treatments. Czako et al (2007) studied rats, rather then dogs, no details were given on the ethical element of any analgesics given to the rats suffering from pancreatitis, oedematous pancreatitis and the necrotising pancreatitis.
Conclusions
A causal relationship between the use of high fat diets and pancreatitis in canines has not been confirmed by these clinical papers. Canines that develop hypertriglyceridaemia (whether primary or secondary) are at a potential risk of developing pancreatitis (acute or chronic), and therefore a diet with an appropriate fat level and appropriate type of fat that does not induce hypertriglyceridaemia would be beneficial from anecdotal evidence (Watson et al, 2010). Higher fat diets have been shown to increase the exocrine pancreatic secretions (Haig, 1970; Yago et al, 1997), and to increase severity of necrotising pancreatitis in rats (Czako et al, 2007).
The type of dietary fat may play a more important role than the overall fat content, but whether this is of benefit in treatment of pancreatitis is not known. Although there is no evidence that restriction of dietary fat alters pancreatic stimulation, restriction of dietary fat in dogs that have a confirmed history of pancreatitis is an important recommendation. Further studies would be required to adequately investigate the feeding of low-fat diets (fat levels and fat types) to all dogs with pancreatitis.
Relevance to veterinary practice
There are no direct control group evidence-based studies to support the use of low fat diets for dogs with (or with predisposing factors for) pancreatitis. More clinical research is required to look at causation links, and whether correlations are in fact causation. Anecdotal evidence by leading specilaists in interal medicine and pancreatitis do support the use of low fat diets, including one of the papers examined. As pancreatitis can lead to extreme abdominal discomfort and in severe forms is fatal, the lack of supporting evidence-based studies should not remove the weighting of anecdotal evidence. Unsupported recommendations often quote diets with less than 10% fat on a dry matter basis (DMB) (less than 17% of calories from fat) to be low fat, while diets with 10 to 15% fat (17 to 23% of calories) are considered to contain a moderate amount of fat. Foods with more than 20% fat are considered high fat. When giving nutritional advice to clients with dogs with pancreatitis, low fat diets (<10% fat on a DMB) should be recommended. Some veterinary diets, designed for dogs with pancreatitis can have levels as low as 4% DMB. Some clients will need guidance on which foods to use or avoid for their pet.