1 How Dietary Deficiency Studies Have Illuminated the Many Roles …
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brewer’s yeast for 61–109 days, and older rats, 150–260 days of age, the deficient
diet for 150–186 days. Control rats were fed the same diet, but supplemented with
butter fat in place of lard. The results showed that consumption of a vitamin Adeficient diet had differential effects on both young and old rats. Many young rats
showed histological changes that increased with days on the diet, but some showed
no observable changes even after 109 days on the diet, and feeding older rats the
deficient diet seemed to produce less striking histological changes. Rats displaying advanced vitamin A deficiency exhibited humped posture, dorsoventral bowing
of the lower cervical and upper thoracic spine, rough coat, emaciation, encrusted
eyelids, and a loss of fat reserves. The organs from these symptomatic rats showed
different degrees of atrophy. The thymus was almost completely missing in the deficient animals, and the testes, parotid, extraorbital gland, and anterior lobe of the
pituitary were approximately 50% smaller than similar organs in vitamin A sufficient controls. Replacement of various epithelia by stratified squamous keratinizing
epithelium was observed in the nares, respiratory mucosa, trachea, bronchi and ducts
of the submaxillary gland, bladder, ureter, uterus, oviducts, cornea, and glands of the
eye. Infection was present in some, but not all deficient rats, but the authors did not
consider infection to be the cause of epithelial changes. Signs of pathology were not
observed in the brain, cerebellum, or sympathetic ganglia. There was no evidence for
effects of vitamin A deficiency on mitochondria, but the authors reported morphological changes in nuclei. Interestingly, they reported that late in deficiency, rats lost
their ability to smell which necessitated force-feeding (Wolbach and Howe 1925).
Several years later, Green and Mellanby found that rats made nutritionally deficient in vitamin A exhibited general visceral atrophy and had less adipose tissue.
Additionally, in contrast with Wolbach and Howe, these investigators reported infective or pyogenic lesions in all but two of the 93 deficient rats studied, that included
abscesses at the base of the tongue and infections of the alimentary tract, urinary
tract, prostate glands and seminal vesicles, nasal sinuses and middle ear. Control rats
fed a vitamin A sufficient diet had no infections. The authors concluded that “the
experimental results are sufficiently impressive to warrant the assumption that vitamin A plays an important part in conferring resistance to many types of infection”
(Green and Mellanby 1928).
Effects of Vitamin A on the Postnatal Nervous System
Early reports showed that vitamin A deficiency led to nerve degeneration and neurological defects (Hughes et al. 1929; Aberle 1934). Studies of rats, rabbits, and
dogs carried out by other laboratories over the next 20 years led to two different
explanations for the genesis of the neural defects. One interpretation was that lack of
coordination and ataxia resulted from lesions in the brain, spinal cord and peripheral
nerves. The contrasting interpretation was that neurological deficiencies were the
consequence of mechanical distortion produced by differential growth rates of the
skeleton and nervous system (Fletcher and Rigdon 1949 and references therein). To
7
brewer’s yeast for 61–109 days, and older rats, 150–260 days of age, the deficient
diet for 150–186 days. Control rats were fed the same diet, but supplemented with
butter fat in place of lard. The results showed that consumption of a vitamin Adeficient diet had differential effects on both young and old rats. Many young rats
showed histological changes that increased with days on the diet, but some showed
no observable changes even after 109 days on the diet, and feeding older rats the
deficient diet seemed to produce less striking histological changes. Rats displaying advanced vitamin A deficiency exhibited humped posture, dorsoventral bowing
of the lower cervical and upper thoracic spine, rough coat, emaciation, encrusted
eyelids, and a loss of fat reserves. The organs from these symptomatic rats showed
different degrees of atrophy. The thymus was almost completely missing in the deficient animals, and the testes, parotid, extraorbital gland, and anterior lobe of the
pituitary were approximately 50% smaller than similar organs in vitamin A sufficient controls. Replacement of various epithelia by stratified squamous keratinizing
epithelium was observed in the nares, respiratory mucosa, trachea, bronchi and ducts
of the submaxillary gland, bladder, ureter, uterus, oviducts, cornea, and glands of the
eye. Infection was present in some, but not all deficient rats, but the authors did not
consider infection to be the cause of epithelial changes. Signs of pathology were not
observed in the brain, cerebellum, or sympathetic ganglia. There was no evidence for
effects of vitamin A deficiency on mitochondria, but the authors reported morphological changes in nuclei. Interestingly, they reported that late in deficiency, rats lost
their ability to smell which necessitated force-feeding (Wolbach and Howe 1925).
Several years later, Green and Mellanby found that rats made nutritionally deficient in vitamin A exhibited general visceral atrophy and had less adipose tissue.
Additionally, in contrast with Wolbach and Howe, these investigators reported infective or pyogenic lesions in all but two of the 93 deficient rats studied, that included
abscesses at the base of the tongue and infections of the alimentary tract, urinary
tract, prostate glands and seminal vesicles, nasal sinuses and middle ear. Control rats
fed a vitamin A sufficient diet had no infections. The authors concluded that “the
experimental results are sufficiently impressive to warrant the assumption that vitamin A plays an important part in conferring resistance to many types of infection”
(Green and Mellanby 1928).
Effects of Vitamin A on the Postnatal Nervous System
Early reports showed that vitamin A deficiency led to nerve degeneration and neurological defects (Hughes et al. 1929; Aberle 1934). Studies of rats, rabbits, and
dogs carried out by other laboratories over the next 20 years led to two different
explanations for the genesis of the neural defects. One interpretation was that lack of
coordination and ataxia resulted from lesions in the brain, spinal cord and peripheral
nerves. The contrasting interpretation was that neurological deficiencies were the
consequence of mechanical distortion produced by differential growth rates of the
skeleton and nervous system (Fletcher and Rigdon 1949 and references therein). To