Beynen AC, 2019. Diet and canine hypercholesterolemia

Abstract

Diet and canine hypercholesterolemia* *Based on article in Dutch (1) Main points A sample of dog blood serum with analysed cholesterol concentration > 7.5 mmol/l points to hypercholesterolemia. The high value may result from intra-individual, spontaneous fluctuation of cholesterol, hypothyroidism, obesity or consumption of a hypercholesterolemic diet. Moreover, hyperresponsiveness to a cholesterol-raising diet (2) or primary hypercholesterolemia (3) can occur in dogs. Dogs are relatively resistant to atherosclerosis. On necropsy of 12,348 dogs, only 21 (0.17%) had atheromatous plaques in their arterial vessel walls (4). Out of 8 animals with intimal cholesterol deposits and known serum cholesterol, six had hypercholesterolemia. During the course of a PhD research project, vascularized, lipid keratopathy was seen in 0.6% of the ophthalmic dog patients (5). About half of the dogs with corneal lipidosis had no detectable abnormalities, while their serum cholesterol ranged from 3.2 to 7.6 mmol/l. As part of the treatment of lipid keratopathy, a low-fat diet is generally recommended (5-10). There are 11 published case observations which, quite apart from their uncontrolled nature, do not demonstrate convincingly that diet therapy ameliorates lipid keratopathy (5, 6, 11). Likewise, serum cholesterol was not conceivably lowered. The degrees to which the habitual amount and composition of dietary fat were changed by diet therapy, is not described. Hypercholesterolemia in dogs seems undesirable, but there are no strong attestations that cholesterol normalization mitigates or prevents certain disorders. In case of secondary hypercholesterolemia, treatment of the disease is indicated. It is unknown whether primary hypercholesterolemia responds to a cholesterol-lowering diet. Experiments show that cholesterol drops after replacement of dietary saturated fatty acids by carbohydrates and/or polyunsaturated fatty acids. In practice, substituting a dry food containing ≤ 8% total fat for a customary diet with higher fat content will normally lower serum cholesterol. Cholesterol metabolism Cholesterol only occurs in animal tissues and products. It is indispensable for the animal body. The lipid is an essential part of cell membranes and is precursor of steroid hormones, bile acids and vitamin D. The dog's skin synthesizes insufficient vitamin D (12) so that dietary intake of the essential is necessary. Lipoproteins in the blood furnish transportation of cholesterol between bodily tissues. In dogs, HDLs (high-density lipoproteins) carry about 50% of total serum cholesterol (13). The input of the body's cholesterol balance comprises cholesterol absorption and synthesis. The output, through bile and intestine into feces, is formed by cholesterol and bile acids, including their

Full text

Dier-en-Arts 2019; Nr 3: 50-51.
Anton C. Beynen
Diet and canine hypercholesterolemia*
*Based on article in Dutch (1)
Main points
A sample of dog blood serum with analysed cholesterol concentration > 7.5 mmol/l points to
hypercholesterolemia. The high value may result from intra-individual, spontaneous fluctuation of
cholesterol, hypothyroidism, obesity or consumption of a hypercholesterolemic diet. Moreover,
hyperresponsiveness to a cholesterol-raising diet (2) or primary hypercholesterolemia (3) can occur
in dogs.
Dogs are relatively resistant to atherosclerosis. On necropsy of 12,348 dogs, only 21 (0.17%) had
atheromatous plaques in their arterial vessel walls (4). Out of 8 animals with intimal cholesterol
deposits and known serum cholesterol, six had hypercholesterolemia. During the course of a PhD
research project, vascularized, lipid keratopathy was seen in 0.6% of the ophthalmic dog patients (5).
About half of the dogs with corneal lipidosis had no detectable abnormalities, while their serum
cholesterol ranged from 3.2 to 7.6 mmol/l.
As part of the treatment of lipid keratopathy, a low-fat diet is generally recommended (5-10). There
are 11 published case observations which, quite apart from their uncontrolled nature, do not
demonstrate convincingly that diet therapy ameliorates lipid keratopathy (5, 6, 11). Likewise, serum
cholesterol was not conceivably lowered. The degrees to which the habitual amount and
composition of dietary fat were changed by diet therapy, is not described.
Hypercholesterolemia in dogs seems undesirable, but there are no strong attestations that
cholesterol normalization mitigates or prevents certain disorders. In case of secondary
hypercholesterolemia, treatment of the disease is indicated. It is unknown whether primary
hypercholesterolemia responds to a cholesterol-lowering diet. Experiments show that cholesterol
drops after replacement of dietary saturated fatty acids by carbohydrates and/or polyunsaturated
fatty acids. In practice, substituting a dry food containing ≤ 8% total fat for a customary diet with
higher fat content will normally lower serum cholesterol.
Cholesterol metabolism
Cholesterol only occurs in animal tissues and products. It is indispensable for the animal body. The
lipid is an essential part of cell membranes and is precursor of steroid hormones, bile acids and
vitamin D. The dog’s skin synthesizes insufficient vitamin D (12) so that dietary intake of the essential
is necessary. Lipoproteins in the blood furnish transportation of cholesterol between bodily tissues.
In dogs, HDLs (high-density lipoproteins) carry about 50% of total serum cholesterol (13).
The input of the body’s cholesterol balance comprises cholesterol absorption and synthesis. The
output, through bile and intestine into feces, is formed by cholesterol and bile acids, including their

bacterial modifications. Balance regulation is illustrated by the metabolic reactions to a cholesterol-
rich diet. In 1953, it was established in the dog that dietary cholesterol inhibits hepatic de-novo
cholesterol synthesis (14). Consumption of a high-cholesterol diet also increases the excretion of
cholesterol and derivatives (15, 16). Cholesterol-rich HDL particles and their liver receptors appear to
attend the supply cholesterol for excretion (17, 18).
Dietary cholesterol and fatty acids
In spite of cholesterol-balance control, high cholesterol intake causes an increase in serum
cholesterol. The dose-response relationship has been investigated fragmentarily in dogs (15, 19-21),
but compilation of the data (Note 1) shows that the addition of 0.44% cholesterol to dry food raises
a group-mean cholesterol level of 5.5 mmol/l to 7.5, the lower limit of hypercholesterolemia. By
comparison, a dry food containing 30% poultry meal, 5% whole egg powder and 2% fish oil has an
estimated cholesterol content of 0.12% in the dry matter (Note 2). A canned dog food was found to
contain 2.5 times as much (2).
According to a cross-over design with feeding periods of two weeks, dogs (n =12) ate diets
containing 60 energy% of a base mixture and 40 energy% coconut fat or sucrose (22). Compared
with coconut fat, sucrose lowered serum cholesterol by 33%. In a similar trial (23) replacement of
coconut fat by safflower oil induced a cholesterol lowering of 16% (n=16). Even though the subject
has not been studied extensively, it appears that serum cholesterol concentration in dogs reacts to
diet change in a species-spanning fashion: cholesterol is lowered by replacement of fats rich in
saturated fatty acids by either isoenergetic amounts of carbohydrates or oils rich in polyunsaturated
fatty acids (22-27).
Commercial foods
In privately-kept, healthy dogs of six breeds, which received one of four commercial dry foods,
serum cholesterol was measured once in each animal (28). The extremes for the averages per food
brand were 4.1 and 6.4 mmol/l (n ≥50/food). About 30% of the dogs in the highest group had a
cholesterol value > 7.5 mmol/l. Possibly, those dogs had a fortuitous upward cholesterol fluctuation
or were hyperresponsive to the food concerned.
Racing huskies with minor infusions of other breeds were fed two commercial dog foods: a dry food
containing 9% fat and 0.08% cholesterol, followed by a canned food with 18% fat and 0.30%
cholesterol, the analysed lipid contents being expressed on the basis of dry matter (2). Six weeks
after the diet change, group-mean serum cholesterol (n=36) was increased from 3.8 to 5.7 mmol/l.
In addition, two separate distributions had formed, with means of 5.3 (n=29) and 7.7 (n=7) mmol/l,
while their starting means (3.7 and 4.0 mmol/l) were hardly different.
The authors combined the outcomes of the feeding trial with those of two comparable experiments,
thus identifying 14 hyperresponders out of a total of 56 dogs (2). Twelve of the 14 hyperresponders
descended from two unrelated bitches. The pattern of inheritance was consistent with an autosomal
dominant gene.
Hypercholesterolemia

A commercial or home-made diet rich in saturated fat and cholesterol may cause
hypercholesterolemia, especially in hyperresponders. Hypercholesterolemia also occurs in obesity,
hyperadrenocorticism, diabetes mellitus and hypothyroidism (29). Dogs with hypothyroidism
probably are extra sensitive to a cholesterol-raising diet (30). Offering excess of dry food induced
obesity and high serum cholesterol in Beagles, whereas providing the same food in restricted
amounts was neither fattening nor cholesterol elevating (31).
It has been suggested that subpopulations of Briards in the United Kingdom (32) and Shetland
Sheepdogs in Japan (33) have primary hypercholesterolemia. The investigated animals were healthy
according to clinical and laboratory examination. The triglyceride concentration in fasting blood
plasma was slightly elevated. Fifteen Briards and 64 Shetland Sheepdogs had mean serum
cholesterol concentrations of 8.0 and 8.6 mmol/l. About 50% of the serum samples contained > 7.5
mmol/l. The diet of the dogs is not described.
Lipid keratopathy
Lipid keratopathy refers to lipid deposition in one or both corneas. The lipidosis is accompanied by
preceding or following vascularisation. In a Boxer with lipid keratopathy a superficial keratectomy
was done (6). In the removed corneal tissue, the concentrations of cholesterol and cholesta-3,5-
diene were six times higher than in normal dogs (34). The Boxer dog had cholesterol and triglyceride
values of 7.0 and 0.7 mmol/l (6).
Lipid keratopathy generally does not go with hypercholesterolemia (5, 6, 11). After feeding an
unspecified, low-fat diet, serum cholesterol was decreased in 2 out of 6 patients and corneal
lipidosis was improved in 6 out of 11 patients (5, 6, 11, Note 3). Serum cholesterol in the above-
mentioned Boxer remained unchanged, but there was substantial clearing of the corneal fat deposits
(6). Three CEA-positive, rough Collie dogs, with lipid keratopathy and serum cholesterol levels of 6.7,
7.8 and 8.3 mmol/l, did not react convincingly to a low-fat dry food with added short-chain fructo-
oligosaccharides (11).
Note 1
Impact of dietary cholesterol (as sole variable) on serum total cholesterol in individual dogs
Ref
Dog ID
Diet cholesterol,
%^
Duration,
weeks
Serum cholesterol,
mmol/l
Base
Test
Base
Test
Base
Test
∆
15
C
0.0033
0.10
58
30
4.8
5.5
0.8
,,
,,
,,
0.60
np
30
,,
8.5
3.7
,,
D
0.0033
0.10
48
43
4.1
5.0
0.9
,,
,,
,,
0.60
np
37
,,
6.0
1.9
19
2947
Cakes
5.0+
8
64
4.6
11.6
7.0
,,
2951
,,
,,
8
64
3.4
10.6
7.2
20
3
-
3
Chow
1.0
np
16
3.9*
9.4
5.5
,,
3
-
4
,,
2.0
np
16
,,
5.6
1.7
,,
2
-
7
,,
5.0
np
28
,,
12.0
8.1
,,
3
-
1
,,
5.0
np
28
,,
15.8
11.9
21
24
C/M#
2.4
>4
>3
3.8
7.8
4.0
,,
25
,,
2.4
>4
>3
5.4
11.6
6.2

,,
36
,,
2.4
>4
>3
4.7
8.0
3.3
^ Added to dry food; np = no pre-experimental period during which the base diet was fed; + dogs
were fed 10 g cholesterol daily together with an estimated amount of 190 g of commercial dog
cakes; *mean value for 22 dogs fed a commercial dog chow. It is assumed that the basic, cholesterol-
free, experimental diet would have induced a similar cholesterol value. That diet contained 66%
sucrose, 10% corn oil, 20% casein and 4% salt mixture; # commercial dog cakes moistened with fresh
milk
Linear regression calculation using the data for added dietary cholesterol (x, % of dry food) versus ∆
serum cholesterol (y, mmol/l) gave the equation: y = 1.38 + 1.40.x (n = 13; r = 0.84)
Note 2
To assess the cholesterol concentration in a dry food containing 30% poultry meal, 5% whole egg
powder and 2% fish oil, the ingredients’ cholesterol contents were assumed to be 150, 1300 and 600
mg/100 g. The food would then hold 122 mg cholesterol/100 g.
Note 3
Impact of a low-fat diet on serum total cholesterol and lipid keratopathy in dogs*
Ref
Dog
BTC
Description of the changes in serum total cholesterol and severity
of lipid keratopathy after switching to a low-fat diet
∆
TC
∆
LK
W/U/B
5
4
6.20
KE + 12 months LF; TC: ?; LK: “mild recrudescence”; “eyes had
changed little one year later”
?
U
,,
14
6.39
KE + 9 months LF; TC: ?; LK: “opacities ... less dense” and “opacity
... incomplete removal ... almost completely disappeared”
?
B
,,
155
6.00
12 months LF; TC = 5.2 mmol/l; LK: “corneal opacities were less
dense”
B
B
,,
65
6.28
KE + 3 months LF; TC: ?; LK: “no recurrence of eye trouble”
?
U
,,
42
6.46
KE + 18 months LF;
TC =
5.80 mmol/; LK: eyes “remained free of
opcacity” and “almost cleared spontaneously”
B
B
,,
133
6.16
? months LF; TC: ?; LK: “cornea continued to clear”
?
B
,,
13
7.60
KE + 9 months LF; TC: ?; LK: eyes “remained clear” and “partial
clearance of the deeper opacification”
?
B
6
6.97
KE + 16 months LF;
TC: “remained relatively unchanged”; LK:
“significant clearing of lipid deposits”
U
B
1
1
3
6.72
CEA; 24 months LF
±
FOS; TC = 8.02 mmol/l; no “worsening of
corneal lipidosis”
W
U
,,
4
7.76
CEA; 24 months LF
±
FOS; TC = 7.37 mmol
/l; no “worsening of
corneal lipidosis”
U
U
,,
5
8.28
CEA; 24 months LF
±
FOS; TC = 8.47 mmol/l; “lipid depositions in
the cornea had become more dense”
U
W
Number of dogs with improvement (B)/total
2/6
6/11
Ref = reference; Dog = identification in publication; BTC = baseline serum total cholesterol
concentration, mmol/l; KE = superficial keratectomy; LF = low-fat diet; CEA = Collie eye anomaly; FOS
= short-chain fructooligosaccharides, 1-3% of dietary dry matter; ∆TC = change in total cholesterol
after diet intervention; ∆LK = change in severity of lipid keratopathy; W = worse (increase), U =
unchanged; B = better (decrease)

*Mean baseline, fasting serum triglyceride concentration of the patients (5, 6, 11; n =11) was 0.51
mmol//l) with range of 0.18 to 0.84 mmol/l. Mean baseline serum total cholesterol was 6.80 mmol/l.
Note 4
In 1964, it was reported that pet dogs had higher serum cholesterol than laboratory dogs (35). In
laboratory dogs (n = 156), mean and range were 3.44 and 1.45 - 6.73 mmol/l. For the pet dogs (n
=160), the values were 5.83 and 2.33 - 25.20 mmol/l. All dogs were apparently healthy. The pet dogs
were typically fed on a commercial dog food supplemented with various human foods. The
laboratory dogs primarily received commercial dry laboratory biscuits and white bread.
Mean serum cholesterol concentrations in healthy pet (n = 12) and working (n = 35) Border Collies
were found to be 5.15 and 3.32 mmol/l (36). Most of the pet dogs were on meat and biscuits,
whereas their working counterparts had a rather uniform diet, consisting mainly of complete, cereal-
based dog food. In a follow-up study, working and pet Border Collies were fed the same diet (37).
Serum total cholesterol of the pet dogs remained broadly unchanged, whereas that of the working
dogs rose, but to a level 15% lower than in the pet dogs. It appears that, apart from diet, serum
cholesterol in the pet and working dogs was also influenced by differences in lifestyle and/or
genetics.
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