All Nutrition Articles Testable Points Flashcards

1
Q

In a study evaluating plasama vitamin D metabolites and CRP in Stage-Stop racing endurance sled dogs JVIM 2015

A

Dogs used as a model for examining effects of exercise on vitamin D status because of their lack of vitamin D synthesis by UV exposure. Inflammatory response of exercise may be associated with hypovitaminosis D

Racing dogs compared to controls

Racing dogs showed significant increase in calcidiol (25 (OH) D3) on day 2 and day 8 of race, while no increases were seen in controls.

Plasma concentrations of 24,25 (OH)D3 (dihydroxycholecalciferol) significantly increased by day 8

No significant changes in calcitriol concnetrations across all time points and groups

Racing dogs ahad signifcantly increased CRP concentrations by day 2 but not day 8

Overall - increases in vitamin D metabolites as well as increases in CRP observed in racing sled dogs - increases in dihydroxycholecalciferol may suggest metabolic variations in dogs that lead to enhanced disposal of vitamin D

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2
Q

What are tight regulators of the active form of vitamin D (calcitriol - or 1,25 (OH)D3?

A

Parathyroid hormone activation of renal 1 alpha hydroxylase

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3
Q

Which diseases have demonstrated low vitamin D concentrations?

A

PLE, renal disease, neoplasia, cardiovascular disease

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4
Q

In a Cohort Study evaluating the success of controlled weight loss programs for obese dogs (JVIM 2015)…

A

Successful weight loss was positively assocaited with a faster rate of weight loss, a longer duration, and feeding a dried weight management diet, but negatively associated with starting body fat and use of dirlotapide (gut selective microsomal triglyceride transfer protein inhibitor)

> 50% of obese dogs on a controlled weight loss program reach their target weight

61% completed program, 31% stopped prematurely, 8% euthanized

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5
Q

In a Study evaluating the association of obesity with serum leptin, adiponectin, and serotonin and gut microflora in beagle dogs (JVIM 2015)…

A

Peripheral leptin, adiponectin, serotonin and CSF serotonin levels measured in beagle dogs free fed vs good restricted
Fecal samples obtained in both groups for 16S rRNA sequencing

Leptin concentrations higher in obese group compared to lean group
Adiponectin and serotonin or CSF (5HT-CSF) concentrations, and TT4 were higher in lean group than in obese group
Leptin, cholesterol, and cortisol levels higher in obese group
Microbiome analysis revealed diversity of microbial community was lower in obese group
phylum firmicutes (85%) were predominant in group in lean dogs
Phylum proteobacteria (76%) were prdominant group in obese dogs

Decreased 5HT levels may increase risk of obesity b.c of increased appetite.

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6
Q

Name three bioactive peptides/ adipokines secreted from adipose tissue

A

Leptin, adiponectin, pro-inflammatory cytokines

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7
Q

Describe the actions of serotonin (5HT) in the body. What is Serotonin’s full chemical name?

A

5 hydroxytriptamine

Biochemical marker of mood and is association with several behavioral and psychological factors

Involved in hypothalamic regulation of energy consumption and serotoin levels in the CNS and is influenced by energy conditions

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8
Q

What is the theory behind the gut brain axis?

A

Gut microbiota can regulate gut/ brain axis. Hypothalamus and brain stem are central sites of appetite regulation, and gut microbiome can stimulate vagal sensory neurons, which is a major neural pathway that conveys information from gastrointestinal luminal contents to the brain and modulates GI motility and feeding behavior.

Gut microbiome can influence neuronal signaling to the brain through vagal afferent neurons

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9
Q

An enrichment of gram negative bacteria predominating in the gut can do what?

A

Influence the level of intestinal LPS (essential cell wall compartoment of gram negative bacteria that triggers systemic inflammation) - and this may be associated with chronic inflammation in obese subjects

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10
Q

In a study evaluating the effect of feeding a weight loss food beyond caloric restrition priord on body composition and resistance to weight gain in dogs. (JAVMA 2015)

A

Attempted determine if feeding a food with coconut oil and supplemental L-carnitine, lipoic acid, lysine, leucine, and fiber on weight loss and maintenance - prospective clinical study

Trial 1 - 30 dogs allocated to three groups to be fed dry maintenance dog food to maintain boy weight, or dry test food at same amount on mass or energy basis

Trial 2 - each of 20 dogs was fed test food and clorici ntake was adjusted to maintain weight loss rate of 1-2%/week

Trial 3- weight maintenance phase

Trial 1 - dogs in groups 2 and 3 lost significantly more weight than those in group 1

Trial 2 - dogs lost a significant amount of body weight and fat mass but retained lean body mass during weight loss phase

Trial 3- continued to lose body fat but gain lean body mass during weight maintenance phase

Metabolomic data evaluation suggested that fat metabolism and lean body mass retention were improved from baseline for dogs fed test food

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11
Q

What are metabolic consequences of obesity?

A

Insulin resistance, hyperlipidemia, low grade inflammation

Heart disease, etc

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12
Q

What body fat percentage is considered ideal in dogs?

A

15-25%

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13
Q

Waht is the primary means for reducing excessive bodyweight in overweight dogs?

A

Calorie restriction

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14
Q

Which dietary fats can increase energy expenditure at the expense of fat deposition

A

Medium chain fatty acids - more readily abosrbed and rapidly oxidized than are long chain fatty acids

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15
Q

Which micronutrients may increase conversion of dietary fat to energy?

A

Carnitine - essential cofactor in transfer of LCFA from cytosol into mitochondria of cells where they undergo beta oxidation - increasing L carnitine intake may increase oxidation of LCFAs

Lipoic acid - directly involved in energy metabolism and has antioxidant effects in reduced forms

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16
Q

Supplementation with which amino acids may reduce protein degradation and reduce loss of lean body mass during periods of restricted energy intake?

A

Lysine and leucine

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17
Q

How do weight loss diets compare to traditional weight loss diets?

A

Weight loss diets contain less energy and fat and ghigher concentrations of essential amino acids, vitamins, minerals, and fiber so that adeqaute nutrition is provided during periods of caloric restriction

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18
Q

Why are dogs and cats unique from humans/ other species in regards to vitamin D synthesis?

A

They lack ability to synthesize vitamin D3 in the skin, likely b/c of high acitvity of 7 dehydrocholesterol delta7 reductase

This means that dogs and cats require dietary supplementation with vitamin d to meet nutritional requirements

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19
Q

What are two dietary forms of vitamin D?

A

Cholecalciferol (vitamin D3) - typically comes from animal food sources

Ergocalciferol (vitamin D2) - plant sources

Cats don’t utilize plant source as easily, dogs can utlize both

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20
Q

What is the path that vitamin D takes once ingested?

A

Transported to liver via the portal system and intestinal lymphatics

Process requires digestive enzymes, chilomicrons, bile acids and VDBP or transcalciferon

After cholecalciferol is tranported to the liver, it is hydroxylated by 25 - hydroxylated by 25 hydroxylase to form 25 (OH)D aka calcidiol/ calcifediol

Calcidiol the binds to VDBP in circulation

Calcidiol - most reliable indicator of systemic vitamin D status in humans

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21
Q

How is vitamin D converted to its most active form (1,25 (OH)2D - Calcitriol)?

A

It is hydroxylated via 1 alpha hydroxylase in the kidney (predominantly) and other tissues that express the enzyme

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22
Q

How is the expression of 1 alpha hydroxylase regulated?

A

Serum concentrations of calcium, PTH, 1,25,OH2D (calcitriol), FGF23, and the klotho gene

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23
Q

How are calcidiol and calcitriol inactivated?

A

By 24 hydroxylase to form 24,25 (OH)2D and 1,24,25-trihydroxyvitamin D and other metabolites that are excreted in urine and bile

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24
Q

Name some roles of vitamin D

A

Influence on Ca-Phos homeostasis via the bone - parathyroid kidney axis, differentiation of immune cells, reductions in inflammation and proteinuria, increases in insulin secretion, improvement of hematopoiesis

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25
Q

Name the mechanisms by which vitamin D can be disrupted in patients with kidney disease.

A

Decreased dietary intake of vitamin D
Decreased enzymatic converstion from cholecalciferol to calcidiol in the liver
Decreased activation via 1 alpha hydroxylase from calcidiol to calcitriol
Increased inactivation of calcidiol and calcitriol
Urinary loss of vitamin D bound to vitamin d binding proteins
Decreased endocytosis of calcidiol into renal cells b/c of decreased megalin expression in proximal renal tubules

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26
Q

Vitamin D metabolites and more significantly decreased in which IRIS stage of CKD?

A

III

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27
Q

What occurs in a patient with CKD mineral bone disorder?

A

Plasma FGF23 concentrations are increased to promote phosphoruresis
Eventually PTH increases to compensate for hyperphosphatemia and secondary hyperparathyroidism occurs

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28
Q

Calcitriol supplementation has been shown to have antineoplastic properties agains which cancers?

A
Osteosarcoma
SCC
Prostatic carcinoma
AGASACA
Mammary gland cancer
MCT
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29
Q

Which vitamin D metabolites have been noted to be decreased in patients with malabsorptive GI disease?

A

Calcidiol and calcitriol

Hypoalbuminemia may contribute to vitamin D loss d/t loss of vitamin D binding proteins

Hypovitaminosis d may also contribute to protein loss through vitamin d effect on immune response

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30
Q

How do calcidiol and calcitriol modulate inflammation?

A

Inhibit production of IL6 and TNFa

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31
Q

What are options for vitamin D supplementation?

A

Ergocalciferol (vit D2), vitamin D3 (cholecalciferol), calcidiol, calcitriol, or vitamin D receptor activators

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32
Q

Run through vitamin D metabolism

A

Cholecalciferol and ergocalciferol from diet —> goes through intestines and enters blood w/ vit D binding protein to be stored in fat cells OR to be activated to calcidiol in the liver by 25-hydroxylase —> calcidiol enters bloodstream again and goes to prox tubule via megalin mediated endoctytosis —> activated to calcitriol by 1 alpha hydoxylase —> calcitriol binds to vitamin D receptor to increase Ca and Phos absorption in gut and Ca resorption from bone

FGF23 and Klotho at kidney act to increase phos excretion and have neg feedback on 1 alpha hydroxylasis, as does increased Ca and Phos

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33
Q

In a study assessing the protein and amino acid concentrations and labeling adequacy of commercial vegetarian diets formulated for dogs and cats (JAVMA 2015)…

A

Cross sectional study evaluating 13 dry and 11 canned vegetarian diets for dogs and cats - crude protein and AA concentration was determined for each diet and compared with AFFCO dog and cat nutrient profiles

Minimum crude protein concentrations for specified species and life stages ere met by 23/24 diets, and remaining diet passed AAFCO feeding trials

6/24 diets did not meet all amino acid minimums, compared with the AAFCO nutrient profiles
1 was below AAFCO minimum requirements in 4AA (leucine, methionin, methionin-cystine, taurine)
2 were below in 3 AAs (methionine, methionine-cystine, and taurine)
2 were below in 2 AAs (lysine, tryptophan
1 was below in tryptophan

Only 3 and 8 diets (wtih and without statement of calorie content as a requirement) were compliant with all pet food label regulations established by AAFCO

**MOST diets assessed in study were not compliant with AAFCO labeling regulations, and concerns raised regarding adequacy of AA content

24% of OTC diets and 100% of veterinary therapeutic diets met all requirements for labeling and nutritional adequacy
96% met clains for minimum crude protein
75% met AAFCO amino acid minimum requirement

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34
Q

Why have vegetarian pet foods been linked to concerns related to nutritional adequacy?

A

Vegetarian protein sources - poor sources for specific essential vitamins (Vit D, Vit A, niacin, cobalamin), fatty acids (arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid), and minerals (calcium, potassium)

Plants are highly variable in protein concentration and provide incomplete AA profiles for pets

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35
Q

Why is taurine an essential aa in cats and only considered conditionally essential in dogs?

A

Cats - Retinal function, cardiac function, reproduction, growth - cannot snythesize it

Dogs - have metabolic capacity to synthesize it when adequate concentrations of sulfer containing AA precursors (methionine, cysteine) are available

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36
Q

What are the 3 means of substantiating claims that pet foods are complete and balanced?

A
  1. To formulate a diet to meet AAFCO dog and cat food nutrient profiles
  2. Conduct a feeding trial by use of AAFCO recognized protocols for specified life stage - if successful, then food is exempt from needing to meet AAFCO nutrient profiles
  3. If in nutritionally similar product family to lead product that has completed AAFCO feeding trial, then lable may state that AAFCO feeding trials substantiate the claim of complete and balanced and nutritional adequacystatements are indistinguishable

If it does not meet these requirements, then must labels as “intended for intermittent or supplemental feeding only”

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37
Q

How do dogs and cats differ from other species in regards to bile acid conjugation?

A

Obligatory bile acid conjugation with taurine

Dogs can synthesize taurine from cysteine and methionine

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38
Q

In a study evaluating integration of a physical training program in a weight loss plan for overweight pet dogs… (JAVMA 2015-2016)

A

Prospective nonrandomized clinical study using 19 client owned overweight or obese ogs

All dogs fed the same calorie restricted diet to achieve weight loss weight of 1-2%/week for 12 weeks

Split into diet only and fitness groups

Fitness and diet group lost a mean of 13.9% body weight, and diet only group lost a mean of 12.9% body weight - not significantly different

Lean body mass was preserved in the fitness and diet group and lost in the diet only group during intervention

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39
Q

In a study evaluating marketing claims, ingredients, and nutrient profiles of OTC diets marketed for skin and coat health of dogs (JAVMA 2015)….

A

Looked at 24 OTC diets (dry and canned)

Most diets incorporated useless marketing terms: digestive health, sensitive or premium
Types and numbers of major ingredients differed
Total number of unique major ingredients in each diet ranged from 3-8
Total number of uniquire ingredients in each diet ranged from 28-68
Concentrations of nutrients assocaited with skin and coat health also differed

Large variation in OTC diet ingredients markened for skin and coat health

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40
Q

What are essential nutrients that can impact skin and coat condition in dogs?

A

Essential fatty acids (play a role in membrane fluidity, metabolic regulation, maintenance of transepidermal water barrier, and eicosanoid syntehsis)

Vitamin A

Minerals

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41
Q

What is the simplest form of carbohydrate?

A

Monosaccharides

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42
Q

What are complex carbohydrates?

A

Oligosaccharides, polysaccharides, starches, dietary fibers

Consist of 3-10 or >10 sugar units

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43
Q

How does carbohydrate digestion occur?

A

Mechanical breakdown of food in mouth (limited production of alpha amylase in mouth of dogs, enzymatic digestion does not start in mouth) —> alpha amylase released by pancreas in dogs allowing for digestion

Once starch is digested, glucose and galactose are actively transported across the mucosal brush border of the SI by sodium dependent glucose transporter 1 (SGLT1) - may be able to upregulate amount of transporter depending on amount of carbohydrates consumed

Once glucose is absorbed it can be used for ATP production by glycolysis, stored in the liver and skeletal muscle as glycogen, or converted to fat and stored as adipose tissue

Glucokinase or hexokinase (or both) are necessary for the first rate limiting step of glycolysis

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44
Q

Run through the steps of glycolysis

A
  1. Glucose phosphorylated to G6P (by hexo/glucokinase - negative feedback of G6P on hexokinase) - 1 ATP used (ATP —> ADP)
  2. G6P converted to fructose 6 phosphate by phosphohexose isomerase — 1 ATP used (ATP —> ADP)
  3. F6P converted to Fructose 1,6 diphosphate (ATP —> ADP)
  4. F1,6,P converteed to dihydroxyacetone phosphate —> converted into two Glyceraldehyde 3 phos (G3P)
  5. Each G3P converted to one pyruvate (total to 2) (2 ATP and 2 NADH GAINED from this)
  6. Pyruvate enters Krebs/ TCA cycle
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45
Q

TCA/ Krebs cycle steps

A
  1. 2 pyruvate —> converted with Co2 to Acetyl CoA (gain 2 NADH)
  2. Citrate —> Isocitrate
  3. Isocitrate + isocitrate dehydrogenase releases CO2 and H+ (converts NAD to NADH) —> alphaketoglutarate
  4. Alpha keto glutarte + alphaketoglutarte dehydrogenase converted to Succinyl-COA (gain one NADH + CO2)
  5. Succinyl COa + succynl CoA snythetase (converts GDP —> GTP) —> succinate
  6. Succinate + succinate dehydrogenase (converts FAD —-> FADH2 with 2 H+ molecules) —> fumarate
  7. Fumarate + fumarase —> malate (1 H2O used)
  8. Malate + malate dehydrogenase —> oxaloacetate
  9. Oxaloacetate + Acetyl CoA + H2O —> citrate (starts over)
46
Q

Which molecule can undergo anaerobic metabolism?

A

Pyruvate + NADH can be converted to lactate via anaerobic glycolysis

47
Q

Which molecule is used for glycogen synthesis?

A

G6P

48
Q

What are the benefits of dietary fiber?

A

Healthy GI, promotes bowel movements, regulates colonic pH, and contributes to growth of beneficial bacteria within the gut
Can be used to reduce energy density of diet, increase satiety, and help promote weight management

49
Q

Why is carbohydrate intake not considered a risk factor in the pathogenesis of diabetes mellitus in dogs?

A

dogs most commonly develope autoimmune destruction of beta cells (I.e. similar totype 1 DM in people) rather than an insulin resistant DM

50
Q

What dietary carbohydrate percentage is acceptable to maintain adequate glycemic control in diabetic dogs?

A

= 55%

51
Q

Why is fiber important in diabetic management?

A

Impairs and slow absorption of dietary glucose on blood, resulting in reduced glycemic responses

Results in smaller fluctuations in blood glucose concentrations when fed diets with a higher percentage of fiber, which may help maintain BG homeostasis

52
Q

In what breed of dog has gluten intolerance been described?

A

Irish Setters

53
Q

Discuss neurologic/ endocrine regulation of food intake

A

Hypothalamus- major region of brain involved in regulation of food intake
Other players - adipose tissue, GI tract, nutrients

In a weight stable/ healthy individual, there is a balance between anorexigenic and orexigenic hormones/signals

After a meal is consumed, anorexigenic signals increase and contribute to satiety

After the time between meals increases, then anorexigenic signals decrease and orexigenic signals increase, which results in a felling of hunger and drive for food intake

During illness, may be shift towards anorexigenic signals taking over

54
Q

Name anorexigenic hormones/ signals and where they come from

A

Leptin/ adipokines (adipose tissue)
Proopiomelanocortin and alpha MSH/ melanocyte stimulating hormone produced in hypothalamus/ pituitary — downregulation of apptite
Serotonin - brain - down regulation/ satiety
Cholecystokinin, GLP-1, peptite YY - GI tract
Insulin, glucagon - pancreas
Inflammatory cytokines, pain, food aversions, bad taste/smell, nutrients, barriers to eating, time of day, compettiion, meds

55
Q

Name orexigenic signals and where they come from

A

Aroma, flavor, texture, time of day, competition, meds
Brain - neuropeptide Y, Agouti related protein, endocannabinoids
GI tract - ghrelin

56
Q

How does food intake become dysregulated in illness?

A

There is altered neural control of appetite as a result of inflammation. Inflammatory cytokines like IL1 and TNFa have anorexigenic effects via various pathways:

  1. Modulation of leptin, corticotripin releasing hormoen and neuropeptide Y
57
Q

In a study evaluating quantification of vitamin D3 in commercial dog foods and comparison with AAFCO recommendations and manufacturer reported concentrations (JAVMA 2018)…

A

81/82 (99%) dry and canned dog food samples evaluated contianed adequate concentrations of Vitamin D3 as outlined in AAFCO recommendations for adequacy, regardless of whether food was formulated to meet AAFCO standards or had undergone AAFCO feeding trial

Vit D3 did not differ significantly between wet dog food formulations and dry food
Analyzed vitamin D3 concentrations did not differ significantly from the manufacturer reported vitamin D3 concentration

58
Q

In a study evaluating the effect of question design on dietary information solicited during vet client interacrtions in companion animal practice in ontario canada (JAVMA 2015)…

A

Most common question type was “what prefaced” e.g. “what kind of food?…) - 76% of questions
Dietary information in client responses was typically restricted to the brand name, subtype, or brand name and subtype of a single food ite,
Question design can influence the accuracyand completeness of nutritional history

59
Q

What are the two dietary forms of vitamin D?

A

Ergocalciferol (VitD2) - pants

Cholecalciferol (vitD3) - animal derived

60
Q

What are consequences of reduced vitamin D?

A

Rickets, osteomalacia, osteoporosis

61
Q

In a study evaluating the nutritional adequacy of recipes for home prepared maintenance diets for cats… (JAVMA 2019) …

A
44% of diets were from veterinarians
Most recipes (99%) contained vague instructions, which necessitated at least 1 assumption regarding ingredients, prep method, or supplementation details to enable analysis
40% did not provide any feeding instructions; the other 60% gave poorly detailed/ unclear feeding instructions
7% home prepped maintenance diet receipes included potentially toxic ingredients like garlic, onions, leeks
None of the recipes provided all essential nutrients in adequate concentrations to meed the NRC recommendations for maintenance of adults cats
Most common nutrients inthe recipes that were below recommended allowance were choline (90%), iron (77%), thiamine (63%), zinc (62%), manganese (57%), vitamin E (57%), copper (46%)
Many recipes (53%) were taurine deficient
Vet authored recipes were less deficient in nutrients than nonvet authored recipes
62
Q

What is an NRC RA - National research council recommended allowance?

A

The concentration or amount of a nutrient in a diet formulated to support a given physiological state and where applicable includes a safety factor for nutrients with uncertain bioavailability

63
Q

What are age related changes to the brain that can occur?

A

Regional atrophy of gray and white matter
Increases in ventricular volume
Loss of neurons and synapses
Reduced neurogenesis
Reduced clearance and accumulation of abnormal proteins (e.g. beta amyloid)
Inflammation
Oxidative stress
Vascular changes
Diminished cholinergic function and alterations in gene expression

64
Q

How much of total body resting energy metabolism does the brain use? What is the brain’s primary source of energy

A

20-25%

Brain uses glucose, but ketones can provide an alternate source during period of starvation

65
Q

What energy sources for the brain can be used to supplement the energy provided by glucose?

A

Ketones and medium chain fatty acids derived from medium chain triglycerides

Ketones (beta hydroxyB and acetoacetate) - derived from FA oxidation, and are able to cross the BBB and mitochondrial membrane and can generate ATP via the TCA cycle and oxidative phosphorylation

Ketone metabolism in the brain does not change with age, but glucose metabolism does

66
Q

What are sources of dietary MCTs?

A

Milk fat, coconut oil, palm kernel oil

Can result in endogenous generation of ketones without requiring a high fat diet

67
Q

Which MCFA can be used for energy by the brain?

A

Octaneoic acid - 8 carbon MCFA - preferentially metabolized for energy, can provide up 20% of brain’s energy needs

68
Q

What are benefits of ketones and MCFA for the brain?

A

Cognitive and neuroprotective effects - provides energy
Oxidative stress
Enhances mitochondrial function and imtrochondrial biogenesis
Increasing concentrations of omega 3 PUFA in the brain
Reducing concentrations of apoptotic inflammators markers
Reducing concentations and toxic effects of amyloid beta
Increasing concentartions of protective neurotrophic factors
Reducing neuronal hyperacitivity and seizure acitivty
Reducing glutaminergic transmission

69
Q

What are the most important b vitamins in neurodevelopment and cognitive function?

A

Thiamine (b1)
Pyridoxine (b6)
Folate (b9)
Cobalamin (b12)

70
Q

What can B vitamin deficiency lead to, and what are the implications of this?

A

High blood concentrations of homocysteine, which is a risk factor for brain atrophy, cognitive dysfunction, and demention

No known benefit/ limited studies in veterinary patients

71
Q

Which omega 3 PUFA play a critical neuroprotective and antiinflammatory role?

A

DHA

72
Q

What are some roles of arginine?

A

Antioxidant function
Metabolized in neurons and other cells to form citrulline, resulting in formation of NO, which serves asa regulator of various physiologic functions, including vascular tone and blood flow, immune responses, neural communication, and expression of antioxidant enzymes

Citrulline derived from arginine is a precursor to compounds that support neurogenesis and is also a precursor to the neurotransmittern GABA

73
Q

Branched chain amino acids are important for brain function how?

A

They play a role in de novo synthesis of glutamate

Play an intrinsic role in maintaining glutamate and GABA stores in the brain
Diets rich in valine, leucine, and isoleucine before and during exercise improves cognitive performance in human athletes

74
Q

What are important functions of L-carnitine?

A

Facilitate transfer of LCFA into mitochondria for beta oxidation
Can enhance mitochondiral function in cardiac and other tissues

Also functions as an antioxidant

75
Q

What is S-adenosylmethionine and why is it beneficial?

A

SAM-E - universal methyl group donor that is believed to play important roles in membrane fluidity, receptor function, and neutrotransmitter turnover and promotion of endogenous antioxidant activity

Supplementation in dogs with cognitive dysfunction may improve activity and awareness

76
Q

What is Apoaequorin?

A

Calcium binding protein that isbelieved to improve age associated intracellular calcium dysregulation that can lead to neurodegeneration and neuronal cell death

Improves performance in attention tasts, not memory

77
Q

What are examples of neutraceuticals used for cognitive dysfunction and how might each benefit?

A

Cysteine and methionine (endogenous antioxidant production)
Inositol - neurotransmitter cofactor
Phosphatidhylserine (membrane quality)
Choline - acetylcholine precursor’
Avocado oil- antioxidant, prserves mitochondrial function
Nicontinamide riboside (NAD precursor)
N-acetylcysteine
Gingko biloba - MAO inhibitor that can increase serotonin and dopamine concentrations

78
Q

What is alpha casozepine?

A

It is derived from bovine milk casein, and is similar in structure to inhibitor neurotransmitter GABA
Exerts benzo like anxiolysis without sedative effects
Can improve some fearful behavior in cats

79
Q

In a Study comparing foods with differing nutritional profiles for long term management of acute nonobstructive idiopathic cystitis in cats(JAVMA 2015) …

A

31 cats with FIC used
Cats fed one of two diets, both indicated for cystitis prevention or control that differed in mineral, antioxidant, and fatty acid profiles
Owners documents LUT signs daily for up to 1 year

6 cats total excluded d/t lack of compliance or GI upset/ food aversion

4/11 cats fed prevention ddiet had >/= 1 recurrent episode of multiple sign days
9/14 cats fed control food had >/= 1 recurrent episode of multiple sign days

Cats fed PREVENTION food had significantly lower mean incidence rates for recurrent episodes of multiple sign days and episodes of hematuria, dysuria, and stranguria as single LUT signs compared with cats fed control food

Cats on prevention food with stranguria 18% - control cats with stranguria 64%, same percentages for dysuria/ hematuria
Fewer cats fed prevention food required analgesia (4/11) - 36% in comparison to cats fed CONTROL food (12/14) (86%)

80
Q

What was the composition of the FIC prevention diet fed to cats in a 2015 JAVMA study?

A

Low magnesium, urinary acidifying, omega 3 FA and antioxidant enriched prevention food

81
Q

In a study evaluating total dietary fiber concentration and composition of commercial diets used for management of DM, obesity, and dietary fat responsive disease in dogs (JAVMA 2015)…

A

Cross sectional study
Evaluated 11 dry and 8 canned canine therapeutic diets
Insoluble and soluble dietary fiber, high molecular weight doluble dietary fiber, and low molecular weivght soluble dietary fiber concentrations were determined. Variables were compared among diets categorized by product guide information, formulation, and regulatory criteria for light and low fat diets.

Soluble dietary fiber (high and low MW) comprised a median of 30% (range 9-54%) of total dietary fiber
LMW soluble dietary fiber - contribute median of 12% (3-34%) of total fiber
Diets for DM management had higher concentartions of insoluble fiber and total fiber with lower proportions of soluble fiber and LMW soluble fiber contributing to total fiber content when compared ith diets for treatment of fat responsive disease
Fiber concentrations varioed within diet categories and between canned and dry versions of the same diet for all pairs evaluated
Diets classified as “light” contained higher total fiber and insoluble fiber than non-light diet
All canned diets were classified as low fat despite providing up to 38% of calories as fat
Many diets may not provide adequate fat restriction for treatment of dietary fat responsive disease

82
Q

Why is the addition of fiber to diets beneficial?

A

Affects ingesta viscosity, GI motility, satiety, nutrient digestibility, and metabolic responses to feeding, as well as colonic bacterial populations and their products

83
Q

How is soluble dietary fiber beneficial in particular?

A

Results in production of short chain fatty acids, some of which are involved in regulation of intetinal production of glucagon like peptide, potentially modulaing appetite, GI motility, and insulin response to a meal

84
Q

In a study evaluating the use of a health belief model to identify factors associated with owner adherence to elimination diet trial recommendations in dogs suspected to have cutaneous adverse food reactions…(JAVMA 2019)…

A

192 dogs prescribed an elimination diet trial
Online survey - anonymous

Of 192 responders:
40% reported 100% adherence to elimination trial recommendations
60% reported <100% adherence to trial
Odds of owners reporting 100% adherence to EDT recommendations were significantly decreased by owner perception of barriers, and were significantly increased by owner knowledge regarding diets and cutaneous adverse food reactions in dogs and by self efficacy or confidence in performing diet trial as directed

Improved owner education/ self suffiency ? may help improve owner compliance

85
Q

In a 2017 JVECC Study evaluating the route and timing of nutrition in dogs with septic peritonitis (2007-2016) - 68 cases …

A

Retrospective study with the goal to determine the impact of the route of nutrition and length of hospitalization and survival to discharge in dogs with sepsis.

Looked at 68 dogs with a septic abdomen that survived >/= 48 hours

Nutritional strategy was categorized into 4 different groups: 1) voluntary, 2) feeding tube, 3) parenteral nutrition 4) combined feeding tube and parenteral nutrition

Overall survival - 54/68 dogs (79%)
Survival prediction index 2 scores were not significantly different between groups
Dogs receiving parenteral nutrition only were less likely to survive than those receiving enteral nutrition (OR 9.7)
Dogs receiving any parenteral nutrition (Even partial) were less likely to survive than other groups and were in hospital significantly longer
Enteral nutrition was associated with survival (OR 9.7)
Metabolic complications associated with PN were frequent but not associated with increased length of hospitalization or survival to discharge

Dogs that received PN may have been sicker than those receiving other forms of nutritional support.

86
Q

When is the use of parenteral nutrition considered in people?

A

When exceeding >/= 7 days in hospital and unable to tolerate >60% of RER by enteral route alone

87
Q

In a JVECC 2016 study evaluating the nutritional analysis and microbiological evaluation of commercially available enteral diets for cats…

A

Objective - to determine prevalence of nutrients less than or greater than accepted standards in commercially available enteral diets for cats, and to identify contamination incidence in enteral diets for cats
Prospective cross sectional study looking a 7 enteral diets for cats

All 7 diets were analyzed for ket nutrients and results were compared to AAFCO nutrient profiles for cats for maintenance and NRC recommended allowance.

4 diets were classified as complete and balanced and 3 diets were classified as not complete and balanced

All diets had at least 1 nutrient less than the AAFCO minimums and the NRC RA

Total number of nutrients less than AAFCO minimums ranged from 3-9 - iron, potassium, and manganese being most common
Some nutrient concentrations were undetectable
No samples developed evidence of contamination

Important aspect. - no diets met all of the min nutrient requirements

88
Q

When should assisted feeding be instituted in an ill/injured animal?

A

If animal has not met RER for 3-5 days, even prior to presentation to hospital

89
Q

In a 2016 JVIM study evaluating the use of capromorelin in hyporexic dogs…

A

Prospective randomized masked placebo controlled clinical study
244 client owned dogs with at least a 2 day history of hyporexia
Dogs were treated daily with capromorelin or a placebo. Owners completed an evaluation of appetite at days 0 and 3-4. Success was defined as appetite improvement at day 3.

Capromorelin improved appetite compared to placebo (69% improvement in capromorelin group, 45% improvement in placebo group)
Mean body weight in capromorelin treated dogs increased compared to placebo (1.8% vs 0.1 % increase)
Adverse reactions occurred in both groups, in >5% of patients, with most common being diarrhea and vomiting

First ghrelin receptor agonist shown to be effective in dogs for appetite stimulation

90
Q

What is ghrelin?

A

Similar in structure to growth hormon, secreted from endocrine cells in stomach and stimulates appetite and food intake

91
Q

What is the MOA of capromorelin?

A

Ghrelin receptor agonist

92
Q

In a 2016 JVIM Study evaluating the Prevalence and Clincal Relevance of Exon 2 deletion of COMMD1 in Bedlington terriers in Korea…

A

105 purebred belington terriers (50 male, 55 female) rom keenels and pet dog clubs in koreafrom 2008-2013
Multiplex PCR was used to detect exon 2 deletion of COMMD1
Clinical analysis was performed on each genetic group, and clinical status of dogs was follow up to estimate survival probability

52/105 (49%) were wild type homozygote - NORMAL COMMD1 gene
47/105 (45%) were heterozygote - NORMAL and mutated gene copy
6/105 (6%) were mutant type homozygote - POSITIVE for genetic mutation
Plasma ALt activity was increased in the mutant type homozygous group >2 YO
Survival probability of the mutant type homozygotes surviving 2.5 years was 0.67 and 4 years was 0.5

Bedlingtons positive for the mutation was low in Korea in comparison to other places, given similar presence of heterozygotes, may establish better breeding program

93
Q

What does the copper metabolism domain containing 1 (COMMD1) gene do?

A

Encodes a protein that functions as a regulator of copper metabolism and homeostasis.

94
Q

What occurs secondary to deletion of exon 2 of COMMD1?

A

Autosomal recessive disorder characterized by high concentrations of copper in the liver (b/c it leads to complete absence of the protein that regulates copper metabolism)

Copper tends to accumulate predominantly in hepatocellular lysosomes of affected terriers due to a genetic disorder in the biliary copper excretion pathway

95
Q

In a 2016 JVIM Study evaluating serum beta hydroxybutyrate concentrations in cats with CKD, hyperthyroidism or hepatic lipidosis….

A

Looked at 28 cats with CKD, 34 cats with hyperthyroidism, and 15 cats with hepatic lipidosis, and 43 healthy controls
Prospective observational study
Serum BHB concentrations were measured at admission in cats iwth CKD, HT, and HL for comparison with RR established using healthy cats. Urine dipstick ketones were compared with serum BHB when possible

BHB was above the RR in 6/28 (21%) of CKD cats, 7/34 (20%) of HT cats, and 11/15 (73%) of cats with hepatic lipidosis
Elevations were mild in the CKD and hyperthyroid groups, but more marked in the hepatic lipidosis group
None of the 11 cats with urine dipsticks performed were ketonuric

96
Q

In a 2016 JVIM study evaluating the effect of moderate dietary protein and phosphate restriction on calcium-phosphate homeostasis in healthy older cats…

A

Looked at 54 healthy client owner cats >/= 9 YO
Prospective double blinded randomized placebo controlled trial
Cats were assigned to test diet (protein and phos restricted) or control and monitored for 18 months
26 cats ate test diet, 28 control

There was a significant effect of diet on urinary fractional excretion of phsophate, plasma PTH (prevented increase), and iCa concentrations (increased concentration), but NOT plasma phosphate, FGF23, or creatinine concentrations

Plasma PTH concentrations did not significantly change in cats fed the test diet, but increased over time in cats fed the control diet.

There was no significant treatment effect of the test diet on teh development of azotemic CKD

There MAY be an impact on renal function and could be useful in early CKD

97
Q

What percentage of nonazotemic cats >/= 9 YO develop azotemic CKD within a 12 month time frame?

A

31%

98
Q

What are the biochemical changes that occur early in CKD mineral bone disorder to maintain a normal serum phosphate concentration in the face of a declining GFR?

A

Stimulation of FGF23 and PTH release to promote phosphaturia

99
Q

In a study evaluating the prevalence of hyperhomocysteinemia in Greyhounds and its association with hypofolatemia and other clinicopathologic variables (JVIM 2017)…

A

Data/ serum samples from 559 greyhounds
Nested case control study
Relationship between hyperhomocysteinemia and hypocobalaminemia and hypofolatemia was evaluated, and its frequency compared between healthy greyhounds and greyhounds with thrombosis and chronic diarrhea

Hypofolatemia identified in 41% (172/423) and was more common in hypocobalaminemic than normocobalamic dogs (49 vs 35%)

Hyperhomocysteinemia was noted in 53/78 (68%) of greyhounds, being more common in hypofolatemic than normofolatemic dogs (88% vs 59% of dogs)

All healthy greyhounds, 70% of those with chronic diarrhea, and 75 % (6/8) of those with thrombosis were hyperhomocysteinemic

Hyperhomocysteinemia association with hypofolatemia may suggest decreased intracellular availability of B vitamins, but the functional implications are unknown

100
Q

What is homocysteine and why is it important?

A

Sulfurated intermediate amino acid that is synthesized from dietary methionin and then either remethylated to methionine or metabolized to cysteine

B vitamines (folate/ b9, cobalamin/ b12, pyridoxine/b6) are essential cofactors for enzymes required for homocysteine metabolism and for redox methylation balance (methoxistasis)

Hyperhomocysteinemia may reflect lack of intracellular availability of cobalamin, folate, or both for synthesis of methionine and represents a sensitive marker for detection of b vitamin deficeincy

101
Q

What is hyperhomocysteinemia associated with in people?

A

Strokes, thromboembolic disease, cardiovascular disease, neurodegenerative disorders, chronic GI disease, metabolic/endocrine disorders, etc

102
Q

In a 2018 JVIM study evaluating water requirements of canine athletes during multi day exercise…

A

Objective was to quantify the water turnover of working dogs during multi day exercise and establish the suitability of SC administration of tracer to determine water turnover
Looked at 15 labs trained for explosive detection duty and 16 huskies trained for racing

Total bodywater (% Body weight) varied from 60+/- 8.6% in minimally conditioned labs to 74 +/- 4.5% in highly conditioned labs
Daily water turnover was as high as 45% of TBW during exercise in cold.  There was no effect of sex or speed on daily water turnover

There was good agreement between results calculated using the indicator dilution approach for total body water calculation or those calculated using semilog linear regression approach when indicator isotop was given IV or SQ

Water requirements are influenced by work done

103
Q

In a 2018 JVIM study evaluating vitamin D receptor expression in dogs …

A

Objective - to define which nonskeletal canine tissues express the vitamin d receptor and to investigate expression in inflamed small intestine

13 nonskeletal tissues collected from 6 dogs

35 dogs with chronic enteropathy and 24 control dogs were prospectively enrolled and duodenal biopsies were evaluated for vitamin d receptor expression

Vitamin d receptor expression was assessed immunohistochemically in all samples using a rate IgGVDR monoclonal antibody. Quantitative RTPCR was also used for duodenal biopsies

Vitamin d receptor expression was assessed by IHC was highest in the kidney, duodenum, skin, ileum and spleen and WEAK in the colon, heart, lymph node, liver, lung, ovary

Gastric and testicular tissue did NOT express receptors

NO statistical difference in duodenal VDR expression between healthy dogs and dogs with chronic enteropathy when quantified by either qPCR

There is a lack of down regulation of vit D receptors in inflamed intestines (contrasting with previous studies in people)

104
Q

Describe the vitamin D receptor and what happens when vit D metabolites bind…

A

Ligand activafted transcription factor, which is specific for vit D metabolites (particularly calcitriol)
Once vit D binds, the cytoplasmic VDR then translocates to the nucleus before heterodimerization with a retinoid X receptor, after which the heterodimer binds to vitamin D response elements

This binding results in recruitment of various other nuclear proteins into a trascriptional complex

This complex initiates and regulates the rate of transcription of target genes by RNA polymerase II

105
Q

What can occur with vitamin d binding to its receptor?

A

Can influence a variety of biological effects including cell differentiation, proliferation, and phenotypic changes

106
Q

In a 2018 JVIM study characterizing paroxysmal gluten sensitive dyskinesia in border terriers using serological markers …

A

Background - paroxysmal gluten dyskinesia (PGSD) in border terriers results from an immunologic response directed against transflutaminase (TG2) and gliadin. This may only be one of many manifestations of gluten sensitivity in this breed.

128 client owned border terriers with various disorders

Prospective study - border terriers with paroxysmal episodes and a normal interictal exam were phenotyped using footage of a representative episode and assigned to three groups : Idiopathic epilepsy, paroxysmal dyskinesia, or other. Serum antibodies against transflutaminase and gliadin were measured in all dogs
Healthy boder terriers formed control group

45 had paroxysmal dyskinesia
28 idiopathic epilepsy
35 other
20 controls

Three overlapping phenotypes found — paroxysmal dyskinesia, signs of GI disease, and dermatopathy

Antigliadin IgG concentrations were increased in the PD group compared with IE, controls, and other conditions
Anti-canine transglutaminase (TG2)-IgA concentrations were increased in the PD group compared with IE group, contgrols, and other

Findings may indicate that paroxysmal gluten sensitive dyskinesia appears to be part of a syndrome of gluten intolerance consisting of episodes of transient dyskinesia, signs suggestive of GI diseae, and dermatologic hypersensitivity

107
Q

What is canine epileptoid cramping syndrome?

A

Form of paroxysmal gluten sensitive dyskinesia (PGSD) of border terriers that is analogous to paroxysmal non-kinesigenic dyskinesia in people

Characterized by episodic combinations of dystonia, ballism, tremor, and athetosis occurring at rest with no loss of consciousness
Episodes begin between 6 weeks and 7 YO, episodes may last a few minutes to hours, with some reporting an association with stress/excitement and others reporting signs during waking from sleep

108
Q

In a study evaluating vitamin D metabolism in dogs with and without hypercalciuric calcium oxalate urolithiasis (JVIM 2019…)

A

Objective - compare serum concentrations of vitamin D metabolites in dogs with and without hypercalciuric CaOx urolithiasis

38 dogs - 19 with, 19 without CAOx urolithiasis and hypercalciuria

Retrospective cross sectional study
Calcidiol, calcitriol, and dihydroxycholecalciferol were measured
Ratios of calcidiol/dihydroxycholecalciferol and calitriol/calcidiol were compared between cases and controls

No significant differences were noted between cases and controls when comparison calcidiol, dihydroxycholecalciferol, calcitriol, and calcitriol/calcidiol ratio

Cases had higher calcidiol/dihydroxycholecalciferol ratios compared to controls. There was an overlap in ranges between cases and controls, but 6 cases (32%) had ratios above the control dog range

There was a modest positive correlation between the ratio of calcidiol/dihydroxycholecalciferol and urinary calcium to creatinine ratios

Data may suggest that decreased conversion of calcidiol to dihydroxycholecalciferol in a subset of dogs with CaOx urolithiasis. Abnormalities in vit D metabolism MAY contribute to stone risk in some dogs

109
Q

In a study evaluating the metabolic profile and c reactive protein concentrations in brachycephalic dogs with upper airway obstruction syndrome (JVIM 2019)

A

Background - obstructive sleep apnea syndrome is assocaited with dyslipidemia, hyperglycemia, and insulin resistance
30 purebred brachycephalic dogs with BAOS

Prospective study - respiratory and digestive signs, airwaay and digestive endoscopic anomalies, presence of absence of tracheal hypoplasia, histologic evaluation of GI tract biopsy specimens, serum concentrations of CRP, fructosamine, insulin, glucose, triglyceride, cholesterol, and plama concentrations of lipoprotein classes

77% of dogs had GI signs - esophgeal deviation, atony of the cardia of the stomach, and distal esophagitis were most common endoscopic anomalies
87% had different degrees of laryngeal collapse
GI histologic evaluation - mostly chronic inflamation
Glucose, fructosamine, triglyceride, cholesterol, CRP, pre-beta, beta lipoproteins, and chylomicrons were increased to a variable extent

Significant associations among clinical signs, anatomic abnormalities, CRP, and metabolic profiles were not found

Overall - clin path variables considered do not offer valuable information in dogs with BAOS

110
Q

In a 2018 JVIM study evaluating daily oral cyanocobalamin supplementation in beagles with hereditary cobalamin malabsorption (Imerslund-Grasbeck syndrome) and how it maintains normal clinical and cellular cobalamin status …

A

3 dogs with hereditary cobalamin malabsorption

Prospective study, daily PO cobalamin supplementation was administered, and health status assessed by owner observations. Methylmalonic acid (MMA) to creatinine concentrations were measured using ultraperformance liquid chromatography tandem mass spectrometry on urine samples collected monthly. Concurrent serum MMA was measured for ONE dog

All dogs remain in good health during PO supplementation
Urine MMA remained low in 2 dogs and highish in one dog
All concurrent serum MMA concentrations before and after month 6 were within the established RR for the one dog

Oral cobalamin appeared to be effective in these three dogs

111
Q

What occurs with vitamin B12 deficiency?

A

Mrtabolic derivatives of cobalamin act as essential cofactors or methylmalonyl CoA mutase, which convert to methylmalonyl CoA to succinyl CoA and methionine synthase, which is required for remethylation of homocysteine.

A decrease in activity of these intracellular enzymes results in increases in methy-malonic acid (MMA) and homocysteine concentrations

112
Q

What is hereditary cobalamin malabsorption (Imerson- Grasbeck syndrome/ IGS)?

A

Cobalamin-intrisic factor complex binds to functional receptor complex composed of amnionless (AMN) and cublin (CUBN) subunits (cubam), a heteromeric, multiligand endocytic receptor, consistenting of 2 proteins (AMN and CUBN). In people, mutations in either ther AMN of CUBN gene lead to cobalamin malabsorption.

This disease is described in Australian shepherds, beagles, border collies, and Giant Schnauzers

It is an autosomal recessive triat caused by 2 distinct AMN mutations in Giant Schnauzers and Australian shephers

Two independent CUBN mutations identified in border collies and beagles

Lethal unless cobalamin supplementation started