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Beynen AC, 2023. Diet and canine cataract

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Dier-en-Arts 2023; Nr 1/2: 14-15.

Anton C. Beynen

Diet and canine cataract*

*Based on article in Dutch (1)

Main points

Cataract is whitening or turbidity of the eye lens, leading to diminished sight. Within the dog
population, the prevalence of the combined stages of perceptible cataract increases with aging up to
± 50% at 9 years of age, and to 100% as from 14 years (2). Risk factors in addition to aging are
heredity, diabetes, intra-ocular inflammation, primary hypoparathyroidism and eye trauma (3). Diet-
related cataract in dogs has been described for both experimental and practical conditions (cf. Note
1- 4).

Diabetic cataract is caused by sorbitol, which is formed from glucose via aldose reductase. Likewise,
enzymatic conversion of galactose, a stereo-isomer of glucose, can give rise to cataract. Progression
of cataract in dogs fed a high-galactose diet was prevented by oral provision of inhibitors of aldose
reductase. An unsuitable milk replacer caused cataract in puppies, likely due to insufficient protein
synthesis. Excessive intakes of galactose and deficient intakes of protein induce different types of
cataract.

A double-blinded, placebo-controlled study in dogs with diabetes offers a tentative suggestion that
oral intake of synthetic alpha-lipoic acid retards the development of cataract. That clinical effect
corroborates the finding that alpha-lipoic acid inhibits aldose reductase. There are some veterinary
dog foods with an undeclared amount of added alpha-lipoic acid (4).

Hyperglycemia and cataract

Diabetic cataract is caused by accumulation of sorbitol in the eye lens. By water attraction of sorbitol
the lens swells and loses transparency. Aldose reductase in the lens converts glucose in sorbitol,
which then turns into fructose via a dehydrogenase. The reductase has a low affinity for glucose and
produces sorbitol only at high blood glucose levels (5, Note 5). With galactose as its more preferable
substrate, the reductase forms the hygroscopic galactitol.

In 1977 Engerman et al. (6) showed that cataract develops in dogs with alloxan-induced diabetes and
inadequate control of blood glucose. Good control prevented cataract. In healthy metabolism, high
intake of glucose does not cause long-lasting high blood levels of glucose. In contrast, high intake of
galactose raises blood galactose for an extended period of time. As would be expected, the above-
mentioned investigators demonstrated that a high-galactose diet induces cataract in dogs (7).

Experimental galactosemia

In a 5-year study (7), dogs (± 2 years old, 11 kg) received a dry food without or with 30% admixed
D(+)-galactose. Cataract remained absent in the 10 controls. The six test dogs developed cataract,
but continued to be visibly healthy. On a scale of 0 (absent) to 4 (fundus visibility limited to the
major retinal vessels) the cataract scores were 1 (n=1), 2 (n=4) or 4 (n=1). Galactose was not
detectable in plasma of the control dogs. In the test dogs, the day peak was 10.7 mmol galactose/l.

Two dog experiments confirmed the cataract-inducing effect of dietary galactose and also support
the crucial role of aldose reductase (8, 9). A high-galactose diet caused cataract, but the severity was
dose-dependently reduced by administration of tablets or capsules with two different inhibitors of
aldose reductase. As component of eye drops, an aldose reductase inhibitor blocked further genesis
of galactose-induced cataract in dogs (10, Note 6).

Cataract in puppies

Galactitol accumulation and cataract formation result from high galactose intake. But lenticular
protein synthesis is affected also. The protein content of the lens is about two times higher than that
of most other tissues. Possibly, the rates of protein build-up in the growing lens and protein turnover
in the adult lens are relatively high. In the clouded lens of galactose-fed rats, protein synthesis was
markedly reduced, which was associated with accumulation of aberrant protein (11, 12).

In 1982, the back-then prevailing idea that milk replacers cause cataract in puppies has been put to
the test (13). Pups of four bitches either stayed with their mother (controls, n=10) or were removed
as from 48 hours post parturition and raised with a milk replacer (test pups, n=12). The authors
excluded inherited cataract. Between control and test puppies there were more differences than
type of milk nutrition only. Moreover, the compositions of dog and artificial milk were multivariable.

Within 8 weeks, 6 of the 12 test pups had cataract, whereas the 10 controls were unaffected. Four
test puppies had visible subcapsular cataract. Chemical analysis showed that the dissolved artificial
milk, compared with dog milk (14), contained about 50% less total protein, including the 10 essential
amino acids. Per unit of dietary energy, the difference was even larger: the milk replacer had a much
higher fat content. It seems that protein deficiency in pups can cause the formation of cataract (cf.
Note 2, 7).

Case reports

Case reports from 1983 and 2002 concern cataract and milk replacers (15, 16). Eight Samoyed pups
of a bitch that died post Caesarian section, received colostrum from a foster dog (15). One day later,
6 pups were changed to artificial milk. After 5 weeks, the pups were weaned and two weeks later
clinically examined. All puppies that drank artificial milk showed nuclear-cortical or cortical cataract.
The two pups on dog milk, which can be seen as controls, did not have lens abnormalities.

Due to agalactia of the bitches, two litters of Newfoundland pups were fed with artificial milk as
from two days after birth (16). In connection with deviant behavior as observed at the age of 8
weeks, cataract was diagnosed in pups of the first parturition. The other pups, which were 3 weeks
old, were also found to have cataract. The condition mainly concerned subcapsular cataract. Analysis
of the milk replacer pointed to a 50% lower arginine content, when compared with dog milk (cf.
Note 8, 9).

Alpha-lipoic acid

Alpha-lipoic acid is part of various enzymes, and thus indispensable for normal metabolism. It is not
an essential nutrient for the dog, which meets its needs by own synthesis (4). Alpha-lipoic acid not
only is a co-factor of enzymes and known antioxidant, but also an inhibitor of aldose reductase (17).
In two double-blinded, placebo-controlled studies (18, 19, cf. Note 10), the effect of orally
administered preparations containing alpha-lipoic acid on cataract progression in dogs with diabetes
has been investigated.

Dogs with diabetes, but as yet without the development of blinding cataract, received via oral
administration either a placebo (n=15) or a commercial preparation (n=15) that, amongst other
compounds, contained alpha-lipoic acid (18). Placebo and test preparation were administered daily
in capsule form. The administered amount of alpha-lipoic acid is not communicated. The average
duration to development of lens opacification was 77 and 278 days for the control and test group.

In a second, comparable study, alpha-lipoic acid was given as the sole test medication (19). Dogs
with diabetes (n=15/group) were daily administered a placebo (5 mg ascorbic acid + 2 mg vitamin
E/kg body weight) or alpha-lipoic acid (2 mg/kg body weight) in capsule form. The dose corresponds
with ± 120 mg alpha-lipoic acid/kg dry food (cf. Note 11). The average duration to development of
lens opacification was 162 and 290 days for the control and test group.

Note 1

This communication focuses on the following aspects of canine cataract: experimental induction by
by galactose feeding, unintentional induction by using unsuitable milk replacers and oral alpha-lipoic
acid as inhibitor of cataract progression. Nine publications have reported that experimental diets
deficient in vitamin B2 (riboflavin) caused cataract in adult dogs and puppies (20-28). For house dogs
fed commercial or home-made diets, deficiency of vitamin B2 has not been reported.

Note 2

Under the title “Types of Cataract in the Dog” and the heading “Deficiency Cataract”, Barnett wrote
in 1972 the following (29):

“Cataract due to a deficiency in the diet is rare in dogs except when produced deliberately in
experimental animals. It can be caused by a deficiency of certain essential amino acids or vitamins,
particularly of the B complex.

The cases described here occurred in foxhounds on a diet containing large quantities of potato crisps
(potato chips) and very little protein. Adult animals remained in apparent good health and with no
eye abnormality but puppies were born with cataract. At postmortem examination the livers were
pale (Fig. 15) and there was also an anemia.

The cataract was bilateral, but often the two eyes were not similar, non-progressive, and several
puppies were affected in a litter. The cataract was mainly nuclear, there were also iris anomalies and
ocular nystagmus.”

Note 3

In 1971, Heywood (30) described the cataracts found in 1064 laboratory Beagle dogs up to the age of
1 year. The dogs were used in toxicological trials. The author focused on differentiating between
spontaneously occurring cataracts and drug-induced cataracts (cf. Note 12).

Note 4
With regard to diet and cataract in humans, Weikel et al. (31) wrote: “Epidemiologic literature
suggests that the risk of cataract can be diminished by diets that are optimized for vitamin C,
lutein/zeaxanthin, B vitamins, omega-3 fatty acids, multivitamins, and carbohydrates: recommended
levels of micronutrients are salutary.”

Note 5

Purified rat lens aldose reductase was incubated for 14 h at 37 °C in sealed vials containing 10 mM
aldose, 10 mM NADPH, 1 mM NADP+, 1 mM DL-isocitrate, 2 mM MgCl2, isocitrate dehydrogenase
(13.8 units) and 0.1 M phosphate buffer, pH 7.8 (5). For xylose, galactose and glucose, the Km
(substrate concentration at which enzyme velocity is half maximal) concentrations were 14, 83 and
204 mM.

Rats aged 3 weeks were given diets consisting of 18% casein, 3% salt mixture, 2% cod liver oil, 6%
butter fat, 10% dried yeast, 26% cornstarch, and 35% monosaccharide (32, 33). The simple sugar was
either glucose, xylose or galactose. All rats fed xylose or galactose developed cataract, whereas their
glucose-fed counterparts did not. The earliest changes, observable with the ophthalmoscope, were
found as from 5 days after beginning of the feeding trial.

High fructose intake by rats induced cataract, which was associated with hyperglycemia and
hypertension (34). The rats received drinking water containing 10% fructose. Cataract caused by
fructose was counteracted by oral administration of alpha lipoic acid at levels of 20 and 40 mg/kg
body weight per day, corresponding with about 200 and 400 mg alpha lipoic acid/kg dietary dry
matter. Alpha lipoic acid also reduced the fructose-induced hyperglycemia and hypertension.

Note 6

The aldose reductase inhibitors used were sorbinil (S-6-fluoro-spirochroman-4-5'-imidazolidine-2',4'-

dione) and M79175 (2-methyl-6-fluoro-spirochroman-4-5'-imidazolidine-2',4'-dione) (8, 9). The
inhibitors were in tablet and capsule form. The inhibitor that was applied topically was defined as a
proprietary topical formulation (10). The source was described as: Kinostat, Therapeutic Vision Inc,
Omaha, Neb, and the University of Nebraska Medical Center, Omaha, Neb.

Note 7

It was common practice that wolf pups, to be sold as pets, are removed from the dam at 2 weeks of
age or earlier, so that the wild instinct would not be imprinted. In a study (14), which covered 5
consecutive springs, the pups were taken from the dam between 7 and 12 days. After weaning, pups
were raised on a commercially-prepared milk replacement diet. Wolves breed only in late winter,
and the pups are born 63 days later; there are usually 4 to 6 pups in a litter.

The total number of pups per treatment were as follows: three pups were suckled by their mother
and one by a foster dog; 10 and 15 pups were fed a milk replacer without and with addition. During
springs 2, 3 and 4, the additions were: vitamin C (n=1), lard (n=1), lactalbumin (n=3), casein + corn oil
(n=1), casein + arginine (1), casein + methionine (1) and lactose (n=1). During the last spring, the
additions were: casein (1), arginine (n=2), tryptophan (n=2) and lactose (n=1).

The pups that drank wolf’s or dog’s milk did not develop lens abnormalities. Lens opacity was
observed in all 10 pups raised on the milk replacer without addition and in the pups fed a milk
replacer with added vitamin C or lard. Supplemental lactalbumin was associated with mild lenticular
opacity, but it should be noted that the protein had settled to the bottom of the nursing bottle. Clear
lenses were seen in the pups that received supplemental lactose and casein plus arginine. Pups fed
the milk replacer with added casein plus corn oil or methionine developed lens opacity.

The outcome of the experiment during the last spring were summarized by the authors as follows:
“All pups except the 2 given supplemental arginine and the 1 pup given supplemental lactose
developed the typical posterior subcapsular opacities adjacent to the Y sutures when examined 7
days after starting the special diets.”

The study consists of four small-scale experiments. It is clear that the feeding of unsupplemented
milk replacers induced cataract formation in the wolf pups. It is a striking observation that the two
pups given supplemental lactose in two different experiments did not develop lens opacity. The
added amount of lactose doubled the amount in the milk replacer, which normally contained 2.6%
lactose as fed. Lactose is a disaccharide consisting of glucose and galactose.

Note 8

In rats, combined dietary restriction of tryptophan and vitamin E disturbed fetal lens development,
leading to unilateral or biliateral lenticular opacities (35). When the maternal diet during gestation
and lactation contained 15% L-tryptophan and 0.25% DL-α-tocopheryl actetate of their amounts in
the control diet, the incidence of lenticular opacities was 33%. When tryptophan or vitamin E was
the sole restricted nutrient, or when both nutrients were sufficient, the incidences were 0, 6 and 0%.

For the four respective dietary treatments, the numbers of litters/progeny evaluated were 19/126,
20/179, 13/111 and 5/31. The diet of the latter group, or the controls, contained 5 g tryptophan and
400 mg vitamin E per kg. In a later study (36) with similar design, the investigators confirmed that
shortage of tryptophan was cataractogenic, but also showed that deficits of phenylalanine/tyrosine
or methionine/cystine were not.

Note 9

In 1948, Knowlton Hall et al. (37) summarized the studies carried out by their research group. The
data showed that young rats fed a diet deficient in protein and one of the 10 essential amino acids
developed general haziness of the lens and different degrees of opacity in the cornea.

Note 10

A retrospective study in dogs (38) suggested that oral antioxidants (the dogs received one of two
commercial preparations) had no significant delaying effect on incipient cataract progression (n= 40,
63 affected eyes), but delayed the progression of senile immature cataract (n= 26, 36 eyes). The two
treatment groups were compared with control groups consisting of 72/93 and 34/41 dogs/eyes that
were not given any supplement. The follow-up period was established until a maximum of 800 days
was reached in all groups.

Note 11

A daily dose of 2 mg alpha-lipoic acid/kg body weight in adult dogs corresponds with ± 120 mg alpha-
lipoic acid/kg dry food (1000/15 x 2). It is assumed that the dogs consumed 15 g dry matter/kg body
weight per day.

Note 12
Experimental cholesterol-lowering agents in the form of HMG-Co A reductase inhibitors produced
subcapsular, lenticular opacities in dogs (39). These side effects were considered attributable to
tissue accumulation of desmosterol, the substrate for the inhibited reductase enzyme.

Note 13

Adult female dogs (n=10; mean body weight, 13.1 kg) received a diet (dry food:canned meat:white
bread = 1:2.3:1 as fed). When assuming that the dogs consumed 15 g dry matter/kg body weight per
day, the diet contained about 0.56% calcium and 0.53% phosphorus on a dry weight basis. After 6
weeks, 10 and 12 phosphate tablets were daily added to the diet for successive periods of 4 and 6
months. The supplements raised dietary total phosphorus contents to 1.42 and 1.58%.

The authors (40) wrote: “No complications developed except for sporadic diarrhea during the first
few days of phosphate supplementation.” At the end of the third feeding period, an ophthalmologic
examination was performed. Scattered calcium deposits were found in the lenses of 8 dogs. In 5 of
those 8 dogs, the calcium deposits were associated with changes compatible with cataracts. The
cataract-like condition self-evidently differs from cataract due high galactose or low protein intake.

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