Low-Carbohydrate Diet Optic Neuropathy
The Medical Journal Of Australia I(1977):65
by C. S. Hoyt III, University of California School of Medicine, and F. A. Billson, Royal Children’s Hospital, Melbourne
Visual loss occurring in two patients taking prolonged carbohydrate-restrictive diets is reported. The clinical data in these patients point to a specific diet deficiency of thiamine, causing a bilateral optic neuropathy. A discussion of current concepts of thiamine deficiency in neuroophthalmic disorders A is presented. It is recommended that patients on low-carbohydrate diets for prolonged periods of time should receive thiamine supplements.
PEOPLE in affluent societies are increasingly faced with the problem of obesity and the dietary regimes used to induce weight loss. Low-carbohydrate diets are commonly employed, such as those described by Harvey, 1 Pennington,2 Jameson and Williams, 3 Stillman and Baker,4 and Atkins. 5 An extensive critique of the misconceptions and potential adverse side effects of this diet was recently published by the Council on Foods and Nutrition of the American Medical Association.6 Among the more serious side effects are the potential risk of developing coronary heart disease as a result of the hypercholesterolaemia and hyperlipaemia induced by this diet.67 An elevation of plasma uric acid levels,8 and significant postural hypotension resulting from the dehydration and salt loss which occurs during this diet9 have also been emphasized. In this report, the writers draw attention to two cases of bilateral optic neuropathy which occurred after prolonged adherence to this dietary regime. The authors suggest that these patients suffered from a nutritional neuropathy directly related to the low-carbohydrate diet; the most likely nutrient deficiency in these cases is of thiamine. The authors believe this is the first time that optic neuropathy has been reported to result from the voluntary restriction of carbohydrate in the diet. Furthermore, these cases seen to show evidence that a pure thiamine deficiency can cause optic nerve dysfunction.
A 33-year-old white jet pilot weighed 248 lb. During deployment on a United States naval aircraft carrier, he decided to adhere to a high protein, low-carbohydrate diet in order to lose weight. He strictly avoided foods containing significant quantities of carbohydrates. He primarily ate cheese, meat, eggs and fish, and only occasionally green leafy vegetables. He took no supplement vitamins. After 5! months, he weighed 185 lb. However, he began to notice numbness and tingling in his toes. Two weeks later, he noted difficulty in following the “meatball” (a red light on the carrier deck which guides the pilot’s landing) on a routine night landing. Three nights later, he experienced a similar difficulty. On the next day he reported for medical evaluation.
His best corrected visual acuity was 6⁄12 in both eyes. He could not read the red/green hues of the Ishihara colour plates witli. either eye. His pupils were both 4 mm in diameter; direct and consensual light reflexes were symmetrically brisk. Examination of the visual fields revealed central scotomata which were more marked to red targets than white. Slit-lamp examination gave an unremarkable result. Both corneal reflexes were brisk. The discs and maculae appeared normal on examination. No nerve fibre abnormalities were detected in either eye. Evaluation in the hospital, four days later, included a complete blood count, erythrocyte sedimentation rate (ESR) test, Venereal Disease Research Laboratory Test (VORL), five-hour glucose tolerance test and serum vitamin B’2 level and serum folate level estimations: the results were all norma!. The serum transketolase level was 6611g/100 ml, the blood cholesterol level was 425 mgflOO ml, and the serum uric acid level was 10.6 mg/IOO m!. Skull X-ray films revealed no abnormalities. Lumbar puncture obtained clear, colourless fluid under no increase in pressure. No pleocytosis or protein abnormality was noted. Urinary screening for heavy metals gave a negative result. The patient was given a regular diet and 50 mg of thiamine daily. Four weeks later, his visual acuity was 6⁄6 in both eyes. He could read all colour plates. Only a small scotoma to red was detected in the right eye. This was not detected two months later. The serum transketolase level was 145 I1g/100 m!. Follow-up examinations over the past three years have revealed no recurrence of his optic nerve dysfunction.
A 36-year-old aircraft mechanic weighed 221 lb. During the same cruise as in Case I, he adopted a high protein, low-carbohydrate diet. He admitted to eating an infrequent slice of bread; otherwise, he restricted his diet to cheese, eggs and red meats. He took 500 mg of vitamin C daily, but no supplementary B vitamins were taken. Four and one-half months later, he noted that he had difficulty walking about the ship at night in the red lighting (used to maintain the flight crews’ night adaption). He specifically stated that it appeared as if the lights were too “dim”. He denied smoking or alcohol consumption. Visual acuity in the right eye was 6⁄18 and in the left eye 6⁄12. He could read the red/green hues of the colour plates with great difficulty. Both pupils were 5 mm in diameter with symmetrical light reflexes. Examination of the visual fields revealed central scotomata in both eyes, and a peripheral constriction in the right eye. Slit-lamp examination gave unremarkable results, except for significant arcus senilis in both eyes. Both corneal reflexes were brisk. The maculae appeared normal. The right disc revealed temporal pallor, and significant decrease in the number of nerve fibres in the papillomacular bundle. Evaluation in the hospital, 10 days later, revealed a normal blood count, a negative VORL test result and normal ESR and serum vitamin B12 and serum folate levels. A flat 5-hour glucose tolerance test curve was thought to reflect the long-standing hepatic carbohydrate deprivation. The serum transketolase level was 60 I1g/1 00 m!. Additional serum levels determined included: cholesterol, 510 mg/l 00 ml, triglycerides, 340 mg/IOO ml, uric acid, 12.1 mgfl 00 m!. Treatment with a regular diet, and 50 mg of thiamine daily was instituted. Six weeks later, the visual acuity was 6⁄12 in the right eye, and 6⁄6 in the left eye. No scotoma was present in the left, but a small scotoma was still detected in the right eye. The disc in the right eye still demonstrated mild temporal pallor. The serum transketolase level was 148 ~g/IOO ml. Three months later, the visual acuity was 6⁄6 minus in the right eye, and 6⁄6 in the left. A scotoma to small red targets was noted in the right eye; the right disc remained unchanged. Repeated examinations over the past three years have revealed similar findings.
The data in both of these cases point to a specific diet-induced deficiency of thiamine, which resulted in a bilateral optic neuropathy. Other diagnostic possibilities included tobacco/ alcohol amblyopia, diabetic or syphilitic optic atrophy, and demyelinating disease. However, neither patient smoked. Alcohol consumption does occur (against regulations) on naval vessels, but rarely at the intensity required to produce neurological disorders. Both patients adamantly insisted they had not consumed excessive amounts of ethanol before their illnesses, and this could be substantiated by interviewing men who lived in the same quarters as the patients.
Specific tests for diabetes and syphilis gave negative results. Bilateral optic neuropathy without other neurological signs is unusual in multiple sclerosis, although not necessarily in Devic’s disease. However, spinal fluid examinations revealed no pleocytosis, or increase in the gamma globulin fraction.
The decrease in the level of trans keto lase, an enzyme requiring thiamine as a coenzyme, indicated a thiamine deficiency state in these patients. I 0 Thiamine is found primarily in whole grains, organ meats, pork and some legumes. I I On a red meat, cheese, and egg diet, intake of thiamine would be reduced significantly. Furthermore, thiamine is heat labile, so that a great deal of it is destroyed during cooking. Williams and co-workers demonstrated that the average American diet, before the introduction of enriched bread and cereal foods, provided thiamine at a level near, or below minimum daily requirements. 12 It seems evident that low-carbohydrate diets provide inadequate levels of thiamine for long-term maintenance of normal tissue function.
Thiamine deficiency is well-established as the aetiology of the Wernicke-Korsakoff syndrome.13 However, optic nerve atrophy is not common in this disorder. It has been postulated that thiamine deficiency is the cause of alcohol amblyopia.14 However, Walsh and Hoyt state, “it seems established that thiamine deficiency alone does not cause degeneration of nerve tissue”. 15 Rodger showed that optic nerve degeneration occurred in rats fed a diet deficient in thiamine. 16 The disorder was more severe if the diet was also deficient in riboflavin. Careful studies in the rat have demonstrated that an isolated deficiency of thiamine can cause peripheral nerve degeneration.17
It seems certain that these two patients were deficient in thiamine, as reflected by the low transketolase levels. McLaren has insisted that a coincidental deficiency of riboflavin, not thiamine, is the primary causative factor in nutritional amblyopia. IS However, it is unlikely that these two men suffered from riboflavin as well as thiamine deficiencies. Riboflavin is found in high concentrations in dairy products and both men ate considerable quantities of cheese throughout the duration of the dietary periods. Vitamin B12 levels were normal, as would be expected, since vitamin B12 is found in large quantities in most meats.
The fact that both men recovered visual function within a few weeks of resuming a normal diet and thiamine supplementation suggests that the optic neuropathies were secondary to some dietary deficiency. It is unfortunate that treatment was not limited to thiamine supplements without any change in diet. Nonetheless, thiamine appears to be the only substance in which the diets were deficient which is known to be essential for normal optic nerve function.
If these were thiamine-deficient optic neuropathies produced by prolonged adherence to a low-carbohydrate diet, why has this entity not been recognized previously? Certainly, there are a great number of Americans and Australians who use the low-carbohydrate diet in attempts to lose weight. The most plausible explanation is that few people remain on this diet for more than a few weeks. Since the requirement for thiamine decreases as carbohydrate intake decreases, I 9 clinically significant thiamine deficiency states will take longer to occur than if these patients were consuming normal levels of carbohydrates (deficient in thiamine).
However, Tolstoi,7 and McClellan and Dubois8 reported the findings of two men who remained on all-meat diets for a year. Neither report indicates that visual dysfunction occurred.
It may be that only certain people are prone to develop pathological changes of the optic nerve, even when thiamine intake is abnormally low. Lessels has shown that about 10% of rats have an area of poor capillary circulation in the immediate by retrobulbar portion of the optic nerve.20 He speculates that some metabolic disorders of the optic nerve may not manifest clinical dysfunction unless there is a preexisting anatomical defect. This explanation has been invoked to explain why nutritional amblyopia is uncommon even in large populations of alcoholics. A comparable situation may hold in the case of low-carbohydrate diet-induced thiamine deficiencies. Nevertheless, optic neuropathy resulting from thiamine deficiency appears to be a documented risk of living on a prolonged low-carbohydrate diet, and it is recommended that thiamine be given to patients on the dietary regime.
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- PENNINGTON, A. W., Treatment of obesity with calorically unrestricted diets, J. elin. Nutr., 1953, I: 343.
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- DREYFUS, P., Blood transketolase levels in tobacco-alcohol amblyopia, Arch. Ophthal., 1965, 74: 617.
- WALSH, F., and HoYT, W., Clinical Neuro-Ophthalmology, Volume I, Williams and Wilkins, Baltimore, 1969: \ 120.
- RODGER, F. C., Experimental thiamine deficiency as a cause of degeneration in the visual pathway of the rat, Brit. J. Ophthal., 1953,
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- McLAREN, D., B vitamins, in Malnutrition of the Eye, 1st edition, Academic Press, New York, 1963: 266.
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- LESSELS, S., Toxic and deficiency optic neuropathies, in Neuro-Ophthalmology, Volume 7, edited by Smith, J. 1.., Mosby, St Louis, 1973.