Learning Discoveries Psychological Services
Rosemary Boon Registered Psychologist
M.A.(Psych), Grad. Dip. Ed. Studies (Sch.Counsel), Grad. Dip. Ed., B.Sc., MAPS, AACNEM.
Nutritional Depletion as a Side Effect of Anticonvulsant Medications
The information below is for educational purposes only. Recent research has shown that few generic brands of vitamins and supplements fulfil the need for a high quality product. It is therefore vital that you discuss your unique needs with your health care professional.
This should serve to highlight the need for interdisciplinary co-operation and interventions according to best pratice in the service of the epileptic population.
Anticonvulsant medications such as barbiturates, phenytoin, carbamazapine, primidone, and valporic acid are known to deplete vital nutrients. Each of these is outlined below along with the vitamins and minerals they are known to deplete.
Barbiturates such as Phenobarbitol or Phenobarbitone can cause depletion of calcium, folic acid, vitamin D, vitamin K, and biotin.
Phenytoin such as Dilantin can deplete a wide range of nutrients including biotin, calcium, folic acid, vitamin B1, vitamin B12, vitamin D and vitamin K.
Carbamazepines such as Tegratol, Teril, Carbium can deplete biotin, folic acid and vitamin D.
Primidone in Mysoline can deplete folic acid and biotin.
Valporic acid in Epilim and Valpro can cause depletion of folic acid, carnitine, copper, selenium and zinc.
Health Implications as a Result of Nutrient Depletion/Deficieny due to Anticonvulsants
Vitamin B1 (Thiamine)
Thiamine enhances circulation and assists in blood formation, carbohydrate metabolism, and the production of hydrochloric acid (needed for proper digestion). Thiamine also optimises cognitive activity and brain function and is needed for proper muscle tone of the intestines, stomach and heart. Thiamine also acts an antioxidant protecting the body from the degenerative effects of aging, alcohol consumption and smoking. A vitamin B1 deficiency results in beriberi, constipation, edema, enlarged liver, fatigue, forgetfulness, gastrointestinal disturbances, heart changes, irritability, laboured breathing, loss of appetite, muscle atrophy, nervousness, numbness of the hands and feet, pain and sensitivity, poor coordination, tingling sensations, weak and sore muscles, general weakness, and severe weight loss.
Blood levels are low in epileptics possibly due to ingestion of anticonvulsants (Krause). Moreover, thiamine deficiency may provoke seizures in predisposed patients(Keyser). It is interesting to note in a double blind crossover study patients who had been on phenytoin alone or in combination with phenobarbital for several years received 50 mg of thiamine daily. After 6 months thiamine, improved the neuropsychological functions in both verbal and non verbal IQ testing were noted (Botez).
Vitamin B12 (Cyanocobalamin)
High dose pyroxidine may benefit patients with recurrent seizures due to acute infectious diseases. In one study of 40 infants and children total response rates in the pyroxidine and control groups were 92.5% and 64% respectively. A highly significant difference. Seizures resolved after around a day in the pyroxidine group and after three days in the control group. No adverse effects of pyroxidine were apparent in the observation period (Jiao, Baumeister & Eggar J).
It is important to note that B vitamins should never be given in isolation and a potent B complex should always be given when single B vitamins are indicated.
Folic Acid (Pteroylglutamic acid- PGA)
Folate metabolism is intimately involved in the epileptogenic process. Experimentally induced seizures deplete brain folate as do anticonvulsants (Smith). It should be noted that results of studies investigating the effects of folate supplementation on seizures have been mixed.
Although considered an amino acid, carnitine is more related to the B vitamins. Unlike true amino acids, carnitine is not used for protein synthesis or a neurotransmitter. Its main function in the body is to facilitate the transport of long-chain fatty acids to the mitochondria where they are burned to provide energy. This is a major source of energy for the muscles. Studies have shown decreased carnitine levels in people suffering from chronic fatigue syndrome. Carnitine works with the antioxidants vitamins C and E to help slow the aging process by promoting the production of acetyl-transferase, an enzyme in the mitochondria of brain cells that is vital for the production of cellular energy there. Unless there is an inherited defect in carnitine synthesis, the body normally makes adequate levels of carnitine provided there are sufficient amounts of iron, vitamin B1, vitamin B6, vitamin C and the amino acids lysine and methionine available. Administration of valporic acid (Epilim) can create a carnitine deficiency, which can cause fatigue, confusion, muscle weakness, cramps, heart pain and obesity. Numerous studies have found that patients taking anticonvulsant medications particularly Epilim have lower plasma levels than controls (Coulter). Furthermore, carnitine deficiency seems to be related to the duration of treatment (Chung).
Magnesium is needed in over 300 chemical reactions in the body and depletion is known to cause marked irritability in the central nervous system which eventually results in seizures. Low levels correlate with increased frequency, poor control and longer duration of seizures. Status epilepticus and EEG abnormalities are also related to low cerebral spinal fluid magnesium levels. Additionally, there is a negative correlation between the serum magnesium level and severity of the epilepsy, with the lowest levels seen in status epilepticus. Moreover, 29 out of 30 epileptic children with grand mal or petit mal seizures who received magnesium and stopped their anticonvulsants showed marked improvement (Barnet). Magnesium is a natural calcium channel blocker and it is known that serum calcium and CSF levels may be elevated and remain so for at least 24 hours. Supplementation with magnesium to correct the deficiency is therefore clearly indicated.
Vitamin C is a one of the antioxidants needed by all cells in the body. Anticonvulsant therapy seems to have a negative influence on plasma levels of vitamin C (Singh). Lower vitamin C levels are associated with poore resuklts in tests of central and peripheral nervous system function including cerebellar disturbances. Both males and females with lower Vit C levels showed a tendency toward macrocytic anemia. (Krause).
Vitamin E (d alpha tocopherol) is a powerful antioxidant that prevents the perioxidation of lipids in the cell membranes. Epileptics on anticonvulsant medications may have reduced plasma alpha tocopherol (Vitamin E) levels and this may be due in part to the use of anticonvulsants. Under double blind conditions vitamin E supplementation has been shown to reduce seizures. In one double blind study of 24 epileptic children with refractory epilepsy, after 3 months 83% of the 12 treated children had a greater than 60% reduction in seizures (and half of these children had 90 to 100% reduction) compared to none of the controls. When the controls were switched to 70 to 100% in all of them (Ogunmekan, Krause).
Studies suggest that brain selenium depletion may trigger seizures and subsequent neural damage due to selenium's important role in the defense of neuronal cells against oxygen radical formation and peroxidative processes (Calomme, Ramakers, Webber).
Zinc deficiency is known to cause seizures (Prasad). Anticonvulsants can cause zinc deficiency either by reducing zinc absorption in the gut through chelation or by causing diarrhoea (Lewis-Jones). Studies on zinc supplementation suggest zinc ions limit the excitatory response in the dentate granule cells of patients with medial temporal epilepsy (Williamson). Furthermore, zinc supplementation has been shown to protect against the development of seizures, suggesting that zinc may be an essential component of a natural, anticonvulsant tissue response to abnormal excitation (Sterman). Australian soils are notably deficient in zinc.
A plethora of vitamin supplements is available over-the counter in health food shops in Australia. However, they come in various forms, combinations and amounts and many do not deliver what they promise. They are available in tablet, capsule, gel-capsule, powder, sublingual, lozenge and liquid forms. Some can also be administered by injection. How quickly they are absorbed and assimilated into the body (bio-availability) depends on the form they are in, whether they are synthetic (laboratory manufactured) or natural (natureís unprocessed food sources) and the ingredients used as fillers. It is highly unlikely that you will find one supplement or brand to cater for all of your needs. For this reason, caution is suggested when buying over-the counter supplements and the need for qualified nutritional advice is paramount.
Aldreman CP, Hill CL (1994): "Abnormal bone mineral metabolism after long term anticonvulasnt treatment. Ann Pharmocother 28 (1): 47-8
Balch, P.A. & Balch, J.F., (2000): Prescriptions for Nutritional Healing (3rd edition), Avery Books, New York
Barnett, LB (1959) Journal of Clinical Physiology 1: 25.
Baumeister, FAM, Eggar J (1996): "Diagnosis and therapy of Vitamin B6 dependent epilepsy". Monatsschr Kinderheilkd 144: 534-5.
Botez MI et al (1993): "Thiamine and folate treatment of chronic epileptic patients: a controlled study with the Wechsler IQ Scale. Epilepsy Res 16 (2): 157-63.
Bregola, G et al (1996): "Biotin deficiency felicitates kindling hyperexcitability" Neuro Report 7 (11): 1745-8.
Calomme MR et al (1996): "Selenium deficiency triggering intractable seizures" Therapeutic Uses of Trace Elements
Vol 62: 359-64
Coulter DL (1995): "Carnitine deficiency in Epilepsy: Risk factors and treatment". J Child Neurology 10 Suppl 2:S32-S39.
Chung S et al (1997): "Alerations in the carnitine metabolism in epileptic children treated with valporic acid". J Korean Med Sci. 12 (6): 553-8.
Flodin NW (1988): Pharmocology of Micronutrients. Alan R List, New York Inc.
Jiao FY et al (1997): "Randomised controlled trial of high dose intravenous pyridoxine in the tresatment of recurrent seizures in children". Pediatr Neurol 17 (1):54-7.
Kogan, VE et al (1983): "Role of lipid peroxidation in damage to serotonin receptors and development of epileptiform seizures during hypoxia". Biull Eksp Biol Med 96 (12) 16-18.
Kovalenko, VM et al (1984): "Alpha tocopherol in the complex treatment of several forms of epilepsy". Zh Neuropathol Psikhitv (in Russian) 6: 892-7.
Krause KH et al (1982): "Reduction of biotin level as a possible factor in the mode of action of anticonvulsants". Arch Psychiatr Nervenkr . 23 (2):141-8 (in German).
Krause KH et al (1986): "B vitamins in Epileptics". Bibl Nutr Dieta. 38:154-67
Krause KH et al (1988): "Effect of long term treatment with antiepileptic drugs on the vitamin status". Drug Nutr Interact. 5 (4) 317-43.
Keyser A (1991): "Epileptic manifestations and vitamin B1 deficiency". Eur Neurol. 31:121-5.
Lewis-Jones MS et al (1985): "Cutaneous manifestations of zinc deficiency during treatment with anticonvulsants". BMJ 29-Z: 603-4.
Mock DM A, Dyken ME (1997): "Biotin catabolism is accelerated in adults receiveng long term therapy with anticonvulsants" Neurology 49 (5):1444-7.
Motta E (1998): "Concentration of copper and ceruloplasmin in serum of patients treated for epilepsy" Wiad Lek 51 (3-4): 156-161 (in Polish).
Ogunmekan AO (1985): "Plasma vitamin E levels in normal children and in epileptic childrenwith and without anticonvulsant therapy: Trop Geog Med 37:175-7.
Ogunmekan AO, Hwang PA (1989): "A randomised double blind, placebo controlled, clinical trial of d-alpha tocopherol (vitamin E) as add-on therapy for epilepsy in children". Epilepsia 30 (1): 84-9.
Ramaekers VT (1994): "Selenium deficiency triggering intractable seizures". Neuro Pediatrics 25 (4):217-23.
Rosciszewzka D et al (1993): "Serum levels of vitamin B12 in epileptic patients treated with carbamazepine (Tegratol)". Neurol Neurochir Pol 27 (5) 671-5 (In Polish).
Singh RB et al (1995): "Dietary intake and plasma levels of antioxidant vitamins in health and disease: A hospital based case controlled study". J Nutr Environ Med 5: 235-42.
Sorrenson JRJ (1979): "Therapeutic uses of copper" Jo Nriagu Ed Copper in the Environment Part 2: Health Effects. John Wiley & Sons, New York.
Salbert BA et al (1993): "Characterisation od seizures associated with biotinidase deficiency". Neurology 43 (7):1351-5.
Smith DB, Obbens EAMT (1997 ): "Antifolate-antiepileptic" in Botez MI & Reynolds BH (Eds.) Folic acid in Neurology, Psychiatry amd Internal Medicine. Raven Press New York.
Sterman MB et al (1988): "Zinc and seizure mechanisms" in Nutritional Modualtion of Neural Function. J Morley & Sterman Eds 307-19. New York Academic Press
Sood SK et al (1993): Serum, CSF, RBC and urinary levels of magnesium and calcium in idiopathic generalised tonic clonic seizures". Indian J Med Res 98: 152-4.
Pelton, R & LaValle (2000): The Nutritional Cost of Prescription Drugs- How to maintain good nutrition while using prescription drugs. P 24-40. Morton Publishing Company.
Prasad AS et al (1965): "Determination of Zinc in biological fluids by atomic absorption, spectrophotometry in normal and cirrhotic subjects". J Lab Clin Med 66:508-16.
Valakami MJ et al (1994): "Bone mineral density measured by dual energy Xray, absorptiometry and novel markers of bone formation and reabsorption in patients on antiepileptic drugs" J Bone Minr Res 9 (5): 631-7.
Webber GF et al (1991): "Glutathione peroxidase deficiency and childhood seizures". Lancet 337: 1443-4.
Werbach M R, MD (1999): Textbook of Nutritional Medicine. Third Line Press Inc. CA
Williamson A, Spencer D (1995): "Zinc reduces dentate granule cell hyperexcitablity in epileptic humans". Neuro Report 6 (11): 1562-4.
The above information is for educational purposes only. Recent research has shown that few generic brands of vitamins and supplements fulfil the need for a high quality product. It is therefore vital that you discuss your unique needs with your health care professional.
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