A new study was released on August 5th 2021 that may provide new insights, and avenues for future research concerning nutritional dilated cardiomyopathy in dogs.
The research centered around biochemical analysis of diets associated with cases of nutritional DCM in dogs, and compared those compounds to those in diets not associated with cases of nutritional DCM. The underlying goal of the study was to identify biochemical compounds that differed between these two diets.
“The study’s primary objective, therefore, was to apply a metabolomics approach to identify biochemical compounds that differ between commercial dog foods that have been associated with canine DCM and in more traditional commercial dog foods.”
Smith et al 2021
Once these compounds are identified veterinary nutritionists and other specialists can look at these compound’s role in metabolism to see if they may be causing nutritional related DCM that we are seeing today.
Overall this study offers a starting point for further research, as feeding trials and further analysis will be needed in order for us to really know which biochemical compound/s are responsible.
So let’s break down this research study, what the research study found, and what implications it has for our dogs!
Selecting the Diets
Two different diet groups were selected for this research study. The first diet-group was nine kibbled diets that have been clinically associated with nutritional-related DCM cases. All diets had at least 3 mentions of pulses, potatoes or sweet potatoes within the top 20 ingredients and were part of the June 2019 FDA report (which mentioned 16 diets associated with cases DCM in Dogs). Called the 3P/FDA Diet Group.
Control diets were also kibbled diets, but had not been associated with nutritional-related DCM cases to the author’s knowledge. These diets followed standards set by the World Small Animal Veterinary Association Global Nutrition Committee’s Guide for Pet Food Selection, and did not contain three mentions of pulses, potatoes or sweet potatoes within the top 20 ingredients.
Two samples of each diet (of the same lot number) and one sample was taken from each bag. Where possible, diets for the 3P/FDA group were obtained directly from owner’s who had dog’s diagnosed with Nutritional DCM. For these diets duplicates were not obtained, instead two samples were taken from the same bag. These owner-supplied diets were stored (opened) for variable time frames prior to testing.
The fact that these diets were stored opened by both the owner and researchers/investigators for potentially longer amounts of time could cause mold growth and other changes to the diet which is not ideal. However, as many of the recipes have changed from companies implicated by nutritional DCM cases - this might be one of the only ways of knowing the route cause.
Step 1: Nutritional Biochemical Analysis
Two samples of each diet were put through analysis using “ultra‐high‐performance liquid chromatography–tandem mass spectroscopy”. Basically individual biochemical compounds were purified, then compared to known purified samples.
Step 2: Comparison of Compounds between diets
- Ingredients were ranked as being absent, low, moderate or high based on the ingredient’s position on the pet food label.
A board certified veterinary nutritionist (Dr. Lisa Freedman) did further analysis on the recipes based on her educational expertise to rank ingredients on their significance within the recipe and identify ingredients that significantly differed between recipes/diet groups.
As recipes are considered proprietary information and are not required to be released to researchers or the public, the researchers had to extrapolate the amounts of certain ingredients within the recipe based on the ingredient’s positioning on the dog food label. We know that ingredients listed first or higher on the ingredients list are a higher proportion of the recipe by weight than those listed lower on the ingredients list. However, manufacturers are known to manipulate the ingredients list in order to market pet foods to consumers allowing for “meat to be the #1 ingredient”. Thus the best way to rank these ingredients accurately is to work with a pet food formulator and specialist in the industry such as a board-certified veterinary nutritionist.
- Ingredients were then given a number 1-9 of how often they were present in a diet. If there was a difference of an ingredient of greater than 5 it was considered a “distinguishing ingredient” of the diet group.
Meaning if we saw 4 mentions of blueberries in the 3P/FDA diets associated with DCM, and 5 mentions of blueberries in the “Control” diets – this was not considered a “distinguishing ingredient” because it was present in both foods in similar amounts. In contrast we might see 7 mentions of rice in the non-DCM associated diets, and 0 mentions in the 3P/FA diets, giving us a difference of 7, which is significant.
Then using statistics and a lot of math – these two ranking systems of the ingredients were applied to the biochemical compounds to allow for further analysis.
Simply put - researchers compared biochemical compounds between diets to see which ones were different. Then they saw which ingredients were significantly different between recipes. Finally they overlaid the biochemical compounds that differed between diets with the ingredients that were significantly different between diets.
A total of 830 biochemical compounds were identified. There was a significant difference between the compounds found in the two different diet groups.
Biochemical Compounds Higher in DCM Implicated Diets:
When comparing the two diet groups the DCM Implicated diets had certain compounds in higher amounts than the non-DCM implicated diets. The largest category were amino acids, plant compounds, and lipids – however a large portion of compounds were still “unknown”, and three of these unknown compounds were only found in the DCM Implicated Diets.
Four Key Areas of Concern with Compounds found Higher in Implicated diets:
- Indirect deficiencies due to nutrient/compound interactions
- Lack of bioavailability of nutrients found in excess due to the compound’s form
- Anti Nutrient factors present in high amounts causing malabsorption of nutrients
- Unnamed compounds within the diet.
One example that the researchers gave was that several of the biochemical compounds found higher in the 3P/FDA (DCM Implicated Diets) have been found in previous research to disrupt carnitine transport. So though carnitine is found in adequate amounts within the DCM implicated diets, if transport/metabolism is disrupted it could cause DCM in Dogs.
- acetyl-D,L carnitine (D isomer of carnitine)
- gamma butyrobetaine (deoxycarnitine)
- 5-aminovaleric acid betaine
“These findings support the possibility that 3P/FDA diets supply biochemical compounds that limit carnitine bioavailability at the level of the mitochondria, interfering with fatty acid oxidation and reducing the heart’s energy supply.”Smith et al 2021
Though the presence of these compounds is concerning it’s possible a combination of factors may contribute to nutritional DCM in Dogs. And as stated – unknown compounds may be another area that needs a lot of further research.
The issue with unknown compounds is simply – we don’t know what they are! We don’t know their role in metabolism, or their effects on the heart. We also do not know if they are potentially toxic to the heart.
“In the current study, a large number of “unnamed” compounds differed between 3P/FDA and non-3P/FDA diets. Additional work is needed to identify them and any potential role they may play in heart function. We are also unable to exclude the possibility that added or naturally occurring chemicals (e.g., pesticides, mycotoxins, and heavy metals) are present as toxic contaminants in the foods, but were not detected through metabolomics.”Smith et al 2021
Further research will be needed in order to evaluate these compounds so we can draw conclusions.
Biochemical Compounds Lower in DCM Implicated Diets:
The DCM Implicated dog foods also had significantly lower amounts of compounds such as certain vitamins (namely B vitamins) and cofactors. Along with four unknown compounds that were only found lower in the DCM Implicated Diets.
“Seven of the 8 vitamins that were significantly lower in 3P/FDA diets were B vitamins: pyridoxine (vitamin B6), thiamine (vitamin B1), folate (vitamin B9), pantothenate (vitamin B5), and riboflavin (vitamin B2) were lower in 3P/FDA diets”Smith et al 2021
The fact the B Vitamins are low within the implicated diets that were tested is concerning – the main reason for this in relation to DCM is that B vitamins are co-factors in metabolism related to cardiac function.
In particular vitamin B6 and B12 are part of carnitine and taurine synthesis – which are important amino acids for heart muscle function. Meaning that with deficiencies in these B vitamins you could end up with heart disease EVEN IF you supplied adequate amounts of these amino acids.
It is important to note that: B-Vitamins are extremely sensitive to storage conditions, and have been known to decrease over time. Several of the DCM implicated diets were stored for possibly extended periods of time OPEN if they were supplied by owners for this study.
By comparing dog food recipes panels of the dog food brands implicated by the FDA to cause diet-associated DCM to those that have not been implicated to cause DCM researchers found four “distinguished ingredients” that were significantly different between diet groups. These were: Peas, Lentils, Chicken/Turkey, and Rice.
(1) peas (present in 9 3P/FDA diets and 4 non-3P/FDA diets)Smith et al 2021
(2) lentils (present in 6 3P/FDA diets and 1 non-3P/FDA diet)
(3) chicken/turkey (present in 1 3P/FDA diet and 8 non-3P/FDA diets)
(4) rice (present in 0 3P/FDA diets and 7 non-3P/FDA diets)
Interesting Potatoes was not actually included on this list. According to researchers, prevalence of this ingredient within the dog foods was just too low to actually see significance (only in 2 of the implicated diets and 1 of the control diets).
Researchers then plotted the prevalence of biochemical compounds against the distinguishing ingredients, and they found that diets high in peas contained a significantly higher level of biochemical compounds found to be high in the DCM implicated diets. They also found that diets high in peas contained significantly lower levels of compounds found low in DCM implicated diets.
“These results suggest that peas represent the ingredient contributing the greatest differences between 3P/FDA and non-3P/FDA diets, and that they are associated with higher concentrations of many compounds (88 named biochemical compounds were significantly higher in the 3P/FDA group and 23 named biochemical compounds that were significantly lower in the 3P/FDA group). Generally, compounds that were higher in the high pea diets are lower in the high chicken/turkey or high rice diets.”Smith et al 2021
This research is really a preliminary study, or a “jumping off point” for further research, and it doesn’t really give us any definitive answers. Several follow-up studies may be needed for us to really fully understand the implications of these biochemical compounds. Even the own researchers stated:
“While we cannot establish with certainty if any of these compounds and ingredients are causal for disease, the findings support peas as a leading possible ingredient associated with diet-associated DCM in dogs.”Smith et al 2021
So what I would really love to see in further research are the following studies:
- A Biochemical analysis of peas and pea-based ingredients used in pet food (things like pea fiber, pea protein, dried peas, fresh peas – all after extrusion). This would confirm the findings of this research as to which compounds actually come from peas, rather than just looking at a correlation. Though it is possible ingredient reactions with peas may create some of these compounds.
- Feeding Trails in Dogs with Peas in graduated amounts from 1% to maybe 30% of the diet while assessing heart-related inflammatory markers and doing echos. This would probably need to be a long-term study of >1-2 yrs. Similar testing to what was done in the research study published earlier this year on DCM in Dogs by Adin et al.
- Further Analysis of Unknown Compounds to identify their roles in metabolism, and see if they are possible cardiotoxic.
- Widespread testing of B-Vitamins on Dog Foods at various points in storage – not just post-manufacturing testing. But at increments of 30 days, 90 days, 6 months and 1 year post manufacturing. Along with testing of diets after opening at 1, 14, 30 and 60 days to look at how they degrade.
What type of further research would you like to see based on this study, and what we know so far about Nutritional DCM in Dogs? What do you think about this research study?
About the Author: Nikki is a Registered Veterinary Technician (Veterinary Nurse) and Dog Mom with over a decade of experience with dogs and cats. Since graduation from college (BS Biology, Dip. Animal Nutrition, AS Animal Science) she has adopted two mixed breed dogs – Ranger and Ash, and has focused her time learning about pet food and nutrition.
Nikki shares information on a range of dog nutrition topics: from how to create a homemade complete and balanced dog food recipes, to how to choose a dog food. Nikki strives to give dog parents the information they need in order to make the best nutrition decisions for their pup!
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