Research interests

  • Interests
    Ketogenic Diet, Epilepsy, Fructose, MCTS, Vitamin D, Nutrition, Vitamin D Deficiency, Mitochondria, metabolic acidosis, Magnesium

Publications

  • 2.48
    Impact points
    Can magnesium supplementation reduce seizures in people with epilepsy? A hypothesis.

    Alan W C Yuen, Josemir W Sander

    Epilepsy research. 03/2012;

    Magnesium is required for over 300 enzyme systems and is critical for many cellular functions including oxidative phosphorylation, glycolysis, DNA transcription and protein synthesis. Studies suggest that the modern Western diet and lifestyle may lead to magnesium deficiency, and this appears to be ... [more] Magnesium is required for over 300 enzyme systems and is critical for many cellular functions including oxidative phosphorylation, glycolysis, DNA transcription and protein synthesis. Studies suggest that the modern Western diet and lifestyle may lead to magnesium deficiency, and this appears to be associated with a wide range of medical conditions. Magnesium deficiency decreases seizure thresholds in animal models of epilepsy and indeed low magnesium concentration in the perfusate is a common method of generating spontaneous epileptiform discharges from rat hippocampal slices. Magnesium is a potential modulator of seizure activity because of its ability to antagonize excitation through the N-methyl-d-aspartate receptor. Some studies have shown that people with epilepsy have lower magnesium levels than people without epilepsy. There are case reports of seizures being controlled with magnesium supplementation in people with specific conditions, and recently in an open randomized trial, children with infantile spasms responded better to adrenocorticotropic hormone (ACTH) plus magnesium than to ACTH alone. We hypothesise that magnesium supplementation can reduce seizures in people with epilepsy. This hypothesis can be tested in a controlled randomised supplementation trial. If proven, magnesium supplementation needs to be considered in the overall management of people with refractory epilepsy.
  • 2.61
    Impact points
    Non-randomized open trial of eicosapentaenoic acid (EPA), an omega-3 fatty acid, in ten people with chronic epilepsy.

    Alan W C Yuen, Dominique Flugel, Annkathrin Poepel, Gail S Bell, Janet L Peacock, Josemir W Sander

    Epilepsy & behavior : E&B. 02/2012; 23(3):370-2.

    This is a non-randomized open assessment of eicosapentaenoic acid (EPA) supplementation in ten people (five males) with refractory focal seizures. Each received 1000mg of EPA daily for 3months. Six people had fewer seizures during the supplementation period compared with baseline (range 12 to 59% re... [more] This is a non-randomized open assessment of eicosapentaenoic acid (EPA) supplementation in ten people (five males) with refractory focal seizures. Each received 1000mg of EPA daily for 3months. Six people had fewer seizures during the supplementation period compared with baseline (range 12 to 59% reduction) and one other person had markedly reduced seizure severity. The mean reduction in seizure frequency was 16% (95% CI - 10% to 35%, p=0.26). With the small number of participants and open nature of the study, interpretation of the results is difficult, but a possible weak effect of EPA on seizures cannot be discounted. Further examination of EPA supplementation should be undertaken with larger numbers of people in controlled trials. Higher doses and longer duration of treatment should be considered.
  • 1.39
    Impact points
    Impaired mitochondrial energy production: the basis of pharmacoresistance in epilepsy.

    Alan W C Yuen, Josemir W Sander

    Medical hypotheses. 07/2011; 77(4):536-40.

    Twenty to thirty percent of people who develop epilepsy continue to have seizures despite antiepileptic drug (AED) treatment. The introduction of many new AEDs in the last two decades does not appear to have reduced substantially the proportion of people who are pharmacoresistant and continue to hav... [more] Twenty to thirty percent of people who develop epilepsy continue to have seizures despite antiepileptic drug (AED) treatment. The introduction of many new AEDs in the last two decades does not appear to have reduced substantially the proportion of people who are pharmacoresistant and continue to have seizures. Currently there are two main mechanisms suggested for pharmacoresistance in people with epilepsy: the transporter and target hypothesis. There are inadequacies in both these hypotheses and alternatives should be considered. There is accumulating evidence from animal studies, human physiological measurements and imaging studies that there is impaired mitochondrial energy production in the epileptogenic zone. Impaired mitochondrial function and lower bioenergetic state is associated with higher extracellular glutamate and increased neuronal hyperexcitability. Conversely, the ketogenic diet effective in reducing seizures, has been shown in animal studies to be associated with up-regulation of mitochondrial genes and increased mitochondrial biogenesis. A human imaging study has also shown improved cerebral energy metabolism in people on a ketogenic diet. Hence, the hypothesis is that the likelihood of seizures occurring results mainly from the interplay of three factors: the seizuregenic potential of the epileptic focus, the efficacy of AEDs and the efficiency of mitochondrial function. This hypothesis can be tested by comparing mitochondrial function in people with epilepsy who are pharmacoresistant with those who have become seizure free. The implication of the hypothesis is that the management of epilepsy should take account of the many drugs, toxins, nutrition and lifestyle factors that are known to affect mitochondrial function.
  • 2.48
    Impact points
    The long-term retention of zonisamide in a large cohort of people with epilepsy at a tertiary referral centre.

    Claudia B Catarino, Emanuele Bartolini, Gail S Bell, Alan W C Yuen, John S Duncan, Josemir W Sander

    Epilepsy research. 05/2011; 96(1-2):39-44.

    Zonisamide (ZNS) is an antiepileptic drug (AED) with multiple putative mechanisms of action. It is chemically unrelated to other AEDs. It has been available in Japan since 1989 but was only licensed in Europe in 2005. Its efficacy and tolerability have been shown in several randomised controlled tri... [more] Zonisamide (ZNS) is an antiepileptic drug (AED) with multiple putative mechanisms of action. It is chemically unrelated to other AEDs. It has been available in Japan since 1989 but was only licensed in Europe in 2005. Its efficacy and tolerability have been shown in several randomised controlled trials, but large studies on long-term performance in Western clinical practice are scarce. We assessed a large cohort of consecutive people who started ZNS at a tertiary epilepsy referral centre, from June 2005 to July 2009. Forty-six percent of the 417 people included were still taking ZNS at last follow-up, with an estimated retention rate at three years of 30%. Almost one third of the population reported a period of improvement in terms of seizure reduction of at least six months duration whilst on ZNS. Sixteen people became seizure free for at least six months and seven of these were seizure free for one year or more. Adverse events occurred in 58%, frequently CNS-related. People on three or more AEDs and people starting zonisamide at 25mg daily rather than 50mg or more, were more likely to discontinue ZNS. Retention rates for ZNS were similar to those previously reported, and comparable to lamotrigine, topiramate, pregabalin, higher than gabapentin, and lower than levetiracetam.
  • 2.48
    Impact points
    Effects of AEDs on biomarkers in people with epilepsy: CRP, HbA1c and eGFR.

    Alan W C Yuen, Gail S Bell, Janet L Peacock, Matthias M Koepp, Philip N Patsalos, Josemir W Sander

    Epilepsy research. 10/2010; 91(2-3):187-92.

    The standardised mortality ratio in people with epilepsy is raised to between 2 and 3 compared with the general population. Some biomarker levels, including higher C-reactive protein (CRP), higher glycosylated haemoglobin (HbA1c) and lower estimated glomerular filtration rate (eGFR), are associated ... [more] The standardised mortality ratio in people with epilepsy is raised to between 2 and 3 compared with the general population. Some biomarker levels, including higher C-reactive protein (CRP), higher glycosylated haemoglobin (HbA1c) and lower estimated glomerular filtration rate (eGFR), are associated with an increase risk of premature mortality. These biomarkers were measured in 125 people with refractory epilepsy to estimate the potential effect of antiepileptic drug (AED) use on these markers. Multiple regression analysis showed that valproate (N=50) use was associated with 55% lower mean CRP concentrations and higher mean eGFR values; and phenytoin (N=32) use with 4% lower mean HbA1c values. These potentially represent health markers improved by AEDs. On the other hand, lamotrigine use (N=48) was associated with 13% lower mean eGFR and this may represent a negative effect on a health marker. These preliminary observations clearly require further controlled studies ideally in people on AED monotherapy.
  • 2.61
    Impact points
    Can slow breathing exercises improve seizure control in people with refractory epilepsy? A hypothesis.

    Alan W C Yuen, Josemir W Sander

    Epilepsy & behavior : E&B. 08/2010; 18(4):331-4.

    Studies on various medical conditions have shown that poor health is associated with lower parasympathetic tone. People with epilepsy appear to have decreased parasympathetic tone, with a greater decrease in those with intractable seizures than in those with well-controlled epilepsy. Slow breathing ... [more] Studies on various medical conditions have shown that poor health is associated with lower parasympathetic tone. People with epilepsy appear to have decreased parasympathetic tone, with a greater decrease in those with intractable seizures than in those with well-controlled epilepsy. Slow breathing exercises have been shown to increase parasympathetic tone in healthy volunteers. Slow breathing exercises have been shown to improve a number of medical conditions including asthma, hypertension, anxiety states, and posttraumatic stress disorder. We hypothesize that slow breathing exercises in people with epilepsy can lead to an increase in parasympathetic tone and an accompanying reduction in seizure frequency. The slow breathing exercises, probably through baroreceptors, chemoreceptors, and pulmonary stretch receptors, affect cortical activity and hence seizure thresholds. It is also possible that slow breathing exercises might reduce seizure frequency by reducing anxiety. The hypothesis can be tested by employing devices and protocols that have been used to reduce breathing rates and have been shown to improve health outcomes in other medical conditions.
  • 2.48
    Impact points
    The long-term retention of pregabalin in a large cohort of patients with epilepsy at a tertiary referral centre.

    Alan W C Yuen, Rinki Singh, Gail S Bell, Anupam Bhattacharjee, Aidan Neligan, Dominic C Heaney, John S Duncan, Josemir W Sander

    Epilepsy research. 10/2009;

    Pregabalin (PGB) is a new antiepileptic drug (AED) which is a structural, non-functional analogue of gamma-aminobutyric acid. It acts at presynaptic calcium channels to modulate neurotransmitter release in the CNS. While the efficacy and tolerability of PGB have been demonstrated in several randomis... [more] Pregabalin (PGB) is a new antiepileptic drug (AED) which is a structural, non-functional analogue of gamma-aminobutyric acid. It acts at presynaptic calcium channels to modulate neurotransmitter release in the CNS. While the efficacy and tolerability of PGB have been demonstrated in several randomised controlled trials, few studies have addressed long-term outcome in large groups of patients. A cohort of patients attending a tertiary referral centre for epilepsy was identified as having started taking PGB. Patients' data were obtained through medical records. Of 402 patients included, 42% of patients were still taking PGB at last follow-up. The estimated 2.5-year retention rate was 32%. Males appeared more likely to continue on PGB therapy than females. The common adverse experiences (AEs) leading to withdrawal were CNS-related, psychiatric AEs and weight gain. Published retention rates for levetiracetam appear to be higher, and those for gabapentin lower, than the rates estimated for PGB.
  • 1.39
    Impact points
    Vitamin D: In the evolution of human skin colour.

    A W C Yuen, N G Jablonski

    Medical hypotheses. 09/2009;

    The natural selection hypothesis suggests that lighter skin colour evolved to optimise vitamin D production. Some authors question if vitamin D deficiency leads to sufficient health problems to act as a selection pressure. This paper reviews the numerous effects of vitamin D deficiency on human heal... [more] The natural selection hypothesis suggests that lighter skin colour evolved to optimise vitamin D production. Some authors question if vitamin D deficiency leads to sufficient health problems to act as a selection pressure. This paper reviews the numerous effects of vitamin D deficiency on human health and argues that vitamin D deficiency is sufficient to pose as a potent selection pressure for lighter skin colour. Vitamin D deficiency manifesting as rickets and osteomalacia are sufficient to impair reproductive success, but additionally, animal studies and some clinical observations suggest that vitamin D may have more direct impact on human fertility. Vitamin D deficiency may lead to a whole host of clinical conditions which impair health and increase mortality rates: increase susceptibility to bacterial and viral infections; rickets, osteomalacia and osteoporosis, with increased risk of falls and fractures; increased risk of cancers; hypertension and cardiovascular disease; maturity onset diabetes; autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and Type 1 diabetes; and gum disease. We submit that at higher latitudes, lighter skin colour evolved to facilitate vitamin D production under conditions of low ultra-violet B radiation in order to avoid a plethora of ill health, reproductive difficulties and early mortality.
  • 2.61
    Impact points
    Erythrocyte and plasma fatty acid profiles in patients with epilepsy: does carbamazepine affect omega-3 fatty acid concentrations?

    Alan W C Yuen, Josemir W Sander, Dominique Flugel, Philip N Patsalos, Lucy Browning, Gail S Bell, Matthias M Koepp

    Epilepsy & behavior : E&B. 03/2008; 12(2):317-23.

    Fatty acids (FAs) determine membrane properties and may affect cardiac and neuronal function. In this study, FA profiles were determined in 56 patients with epilepsy who participated in a 12-week double-blind randomized trial of omega-3 FA supplementation (1 g eicosapentaenoic acid and 0.7 g docosah... [more] Fatty acids (FAs) determine membrane properties and may affect cardiac and neuronal function. In this study, FA profiles were determined in 56 patients with epilepsy who participated in a 12-week double-blind randomized trial of omega-3 FA supplementation (1 g eicosapentaenoic acid and 0.7 g docosahexaenoic acid daily). At baseline, subjects on carbamazepine (CBZ) had lower docosahexaenoic acid levels, lower levels of long-chain omega-3 FAs, and a lower Omega-3 Index (a risk factor for coronary heart disease mortality), whereas those on oxcarbazepine had higher total polyunsaturated FAs and a higher Omega-3 Index. Following omega-3 FA supplementation, the Omega-3 Index, eicosapentaenoic acid, and docosahexaenoic acid concentrations significantly increased. Patients on CBZ exhibited a less favorable FA profile, associated with a greater risk of coronary heart disease mortality. As arrhythmias are thought to be an important mechanism in coronary heart disease mortality and sudden unexplained death in epilepsy (SUDEP), the effect of CBZ effect in reducing omega-3 FAs might potentially explain some cases of SUDEP among patients prescribed CBZ.
  • 2.53
    Impact points
    A 31-phosphorus neurospectroscopy study of omega-3 long-chain polyunsaturated fatty acid intervention with eicosapentaenoic acid and docosahexaenoic acid in patients with chronic refractory epilepsy.

    B K Puri, M J Koepp, J Holmes, G Hamilton, A W C Yuen

    Prostaglandins, leukotrienes, and essential fatty acids. 09/2007; 77(2):105-7.

    The aim of this study was to determine whether supplementation with the n-3 long-chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid in patients with chronic refractory epilepsy is associated with beneficial changes in cerebral biochemistry. In a 3-month pilot randomized... [more] The aim of this study was to determine whether supplementation with the n-3 long-chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid in patients with chronic refractory epilepsy is associated with beneficial changes in cerebral biochemistry. In a 3-month pilot randomized double-blind placebo-controlled study, three patients received eicosapentaenoic acid and docosahexaenoic acid daily and four received a placebo. 31-Phosphorus neurospectroscopy showed a decrease in phosphodiesters, an increase in gammaNTP and an increase in the broadband component in the active group over this period, while the opposite changes occurred in the placebo group. Therefore, in chronic refractory epilepsy, omega-3 supplementation may be associated with reduced membrane phospholipid breakdown in the brain, an improvement in brain energy metabolism, and an increased level of phospholipids in membranes and/or vesicle bilayers in cells in the brain. The unfavourable biochemical changes observed in the placebo group may be a feature of chronic intractable epilepsy.
  • 2.61
    Impact points
    Mortality and morbidity rates are increased in people with epilepsy: is stress part of the equation?

    Alan W C Yuen, Pamela J Thompson, Dominique Flugel, Gail S Bell, Josemir W Sander

    Epilepsy & behavior : E&B. 03/2007; 10(1):1-7.

    People with epilepsy (PWE), particularly those with more severe seizures, are at risk of premature death. The contribution of deaths unrelated to epilepsy to this risk is likely to be significant. Recent studies indicate that comorbid conditions are similarly increased in PWE. The reason for these i... [more] People with epilepsy (PWE), particularly those with more severe seizures, are at risk of premature death. The contribution of deaths unrelated to epilepsy to this risk is likely to be significant. Recent studies indicate that comorbid conditions are similarly increased in PWE. The reason for these increases in unrelated deaths and comorbid conditions is unclear. In this article, we argue that having seizures is psychologically stressful, and that this stress can lead to a whole range of pathophysiological changes that may trigger various physical illnesses. Hence, psychological stress may be a significant factor contributing to the increase in mortality and comorbidity rates in PWE. This speculation is unlikely to be proven at this stage because of the complexity of the trials required. In PWE who continue to have seizures, more needs to be done to help them cope with the stress. Additionally, attention needs to be paid to improve nutritional status and physical fitness. These steps are likely to enhance the overall health of PWE and may reduce premature mortality and comorbidity rates.
  • 2.61
    Impact points
    Low-grade chronic metabolic acidosis is a contributory mechanism in the development of chronic epilepsy.

    Alan W C Yuen

    Epilepsy & behavior : E&B. 04/2006; 8(2):347-9.

    In most people with epilepsy, the condition is readily controlled, but 20-30% develop chronic epilepsy. An estimated 80,000 patients with epilepsy require ongoing specialist care in the United Kingdom. Nutrition may be a factor in the development of chronic epilepsy. Modern Western diets are thought... [more] In most people with epilepsy, the condition is readily controlled, but 20-30% develop chronic epilepsy. An estimated 80,000 patients with epilepsy require ongoing specialist care in the United Kingdom. Nutrition may be a factor in the development of chronic epilepsy. Modern Western diets are thought to produce a low-grade chronic metabolic acidosis. The hydrogen ion, H+, is a potent modulator of NMDA-activated currents, and in cultured neurons, increased external [H+] strongly suppresses these currents. The effect of chronic metabolic acidosis in vivo has not been fully studied. It is possible that low-grade chronic metabolic acidosis chronically inhibits the NMDA-activated currents, and this may lead to upregulation of the NMDA receptor. This would result in a greater hyperexcitable state and may contribute to the development of chronic epilepsy.
  • 4.87
    Impact points
    The long term retention of levetiracetam in a large cohort of patients with epilepsy.

    C Depondt, A W C Yuen, G S Bell, T Mitchell, M J Koepp, J S Duncan, J W Sander

    Journal of neurology, neurosurgery, and psychiatry. 02/2006; 77(1):101-3.

    Levetiracetam (Lev) is a new antiepileptic drug with a distinct mechanism of action, shown in regulatory trials to be effective. These controlled trials do not always predict how useful a drug will be in day to day clinical practice. Retention rates can provide a better indication of efficacy and to... [more] Levetiracetam (Lev) is a new antiepileptic drug with a distinct mechanism of action, shown in regulatory trials to be effective. These controlled trials do not always predict how useful a drug will be in day to day clinical practice. Retention rates can provide a better indication of efficacy and tolerability in everyday use. Patients attending a tertiary referral centre for epilepsy and who received Lev in the first 2 years of its marketing were assessed (n = 811) to determine continuation rates of treatment with this drug. At the last follow up, 65% of patients were still taking Lev, and the estimated 3 year retention rate was 58%. In total, 11% attained seizure freedom of at least 6 months. Patients taking greater numbers of concurrent antiepileptic drugs (AEDs) were more likely to discontinue Lev, and those reaching higher maximum daily dosages were less likely to discontinue Lev. The retention rate for Lev compares favourably with that of other new AEDs.
  • 2.61
    Impact points
    Omega-3 fatty acid supplementation in patients with chronic epilepsy: a randomized trial.

    Alan W C Yuen, Josemir W Sander, Dominique Fluegel, Philip N Patsalos, Gail S Bell, Tony Johnson, Matthias J Koepp

    Epilepsy & behavior : E&B. 10/2005; 7(2):253-8.

    Animal studies and a preliminary clinical observation suggest that nutritional supplementation with long chain omega-3 fatty acids (omega-3 FAs) may be useful in the nonpharmacological treatment of patients with epilepsy. Omega-3 FAs increase seizure thresholds, and lower inflammatory mediators, whi... [more] Animal studies and a preliminary clinical observation suggest that nutritional supplementation with long chain omega-3 fatty acids (omega-3 FAs) may be useful in the nonpharmacological treatment of patients with epilepsy. Omega-3 FAs increase seizure thresholds, and lower inflammatory mediators, which are increased in patients with epilepsy. In this first randomized, placebo-controlled parallel group trial of omega-3 FA supplementation with 1 g eicosapentaenoic acid (EPA) and 0.7 g docosahexaenoic acid (DHA) daily, 57 patients completed a 12-week double-blind phase. Seizure frequency was reduced over the first 6 weeks of treatment in the supplement group, but this effect was not sustained. The supplementation produced a significant increase in EPA and DHA concentrations and a reciprocal fall in arachidonic and linoleic acid concentrations. No change in serum AED concentrations was detected. Further studies are required to examine different omega-3 FA preparations, different doses, longer treatment duration, and larger sample sizes.
  • 2.23
    Impact points
    Is omega-3 fatty acid deficiency a factor contributing to refractory seizures and SUDEP? A hypothesis.

    Alan W C Yuen, Josemir W Sander

    Seizure : the journal of the British Epilepsy Association. 04/2004; 13(2):104-7.

    Epilepsy, the commonest serious neurological condition, is associated with an increased risk in premature deaths, including an estimated 500 sudden unexpected deaths (SUDEP) per year in the UK. In some patients seizures are associated with cardiac arrhythmias, which are thought to be a major factor ... [more] Epilepsy, the commonest serious neurological condition, is associated with an increased risk in premature deaths, including an estimated 500 sudden unexpected deaths (SUDEP) per year in the UK. In some patients seizures are associated with cardiac arrhythmias, which are thought to be a major factor in SUDEP. Omega-3 fatty acids have been shown to reduce cardiac arrhythmias in animal studies and to reduce sudden cardiac deaths, thought to be due to cardiac arrhythmias, in both healthy subjects and in those who have had one myocardial infarction. Additionally, omega-3 fatty acids in animal studies and in a small clinical observation study have shown anti-seizure effects. Omega-3 fatty acid supplementation in patients with refractory seizures may reduce seizures and seizure associated cardiac arrhythmias and hence SUDEP.
  • Can slow breathing exercises improve seizure control in people with refractory epilepsy? A hypothesis

    Alan W.C. Yuen, Josemir W. Sander

    Epilepsy & Behavior.

    Studies on various medical conditions have shown that poor health is associated with lower parasympathetic tone. People with epilepsy appear to have decreased parasympathetic tone, with a greater decrease in those with intractable seizures than in those with well-controlled epilepsy. Slow breathing ... [more] Studies on various medical conditions have shown that poor health is associated with lower parasympathetic tone. People with epilepsy appear to have decreased parasympathetic tone, with a greater decrease in those with intractable seizures than in those with well-controlled epilepsy. Slow breathing exercises have been shown to increase parasympathetic tone in healthy volunteers. Slow breathing exercises have been shown to improve a number of medical conditions including asthma, hypertension, anxiety states, and posttraumatic stress disorder. We hypothesize that slow breathing exercises in people with epilepsy can lead to an increase in parasympathetic tone and an accompanying reduction in seizure frequency. The slow breathing exercises, probably through baroreceptors, chemoreceptors, and pulmonary stretch receptors, affect cortical activity and hence seizure thresholds. It is also possible that slow breathing exercises might reduce seizure frequency by reducing anxiety. The hypothesis can be tested by employing devices and protocols that have been used to reduce breathing rates and have been shown to improve health outcomes in other medical conditions.
  • Omega-3 fatty acid supplementation in patients with chronic epilepsy: A randomized trial

    Alan W.C. Yuen, Josemir W. Sander, Dominique Fluegel, Philip N. Patsalos, Gail S. Bell, Tony Johnson, Matthias J. Koepp

    Epilepsy & Behavior.

    Animal studies and a preliminary clinical observation suggest that nutritional supplementation with long chain omega-3 fatty acids (omega-3 FAs) may be useful in the nonpharmacological treatment of patients with epilepsy. Omega-3 FAs increase seizure thresholds, and lower inflammatory mediators, whi... [more] Animal studies and a preliminary clinical observation suggest that nutritional supplementation with long chain omega-3 fatty acids (omega-3 FAs) may be useful in the nonpharmacological treatment of patients with epilepsy. Omega-3 FAs increase seizure thresholds, and lower inflammatory mediators, which are increased in patients with epilepsy. In this first randomized, placebo-controlled parallel group trial of omega-3 FA supplementation with 1 g eicosapentaenoic acid (EPA) and 0.7 g docosahexaenoic acid (DHA) daily, 57 patients completed a 12-week double-blind phase. Seizure frequency was reduced over the first 6 weeks of treatment in the supplement group, but this effect was not sustained. The supplementation produced a significant increase in EPA and DHA concentrations and a reciprocal fall in arachidonic and linoleic acid concentrations. No change in serum AED concentrations was detected. Further studies are required to examine different omega-3 FA preparations, different doses, longer treatment duration, and larger sample sizes.
  • Mortality and morbidity rates are increased in people with epilepsy: Is stress part of the equation?

    Alan W.C. Yuen, Pamela J. Thompson, Dominique Flugel, Gail S. Bell, Josemir W. Sander

    Epilepsy & Behavior.

    People with epilepsy (PWE), particularly those with more severe seizures, are at risk of premature death. The contribution of deaths unrelated to epilepsy to this risk is likely to be significant. Recent studies indicate that comorbid conditions are similarly increased in PWE. The reason for these i... [more] People with epilepsy (PWE), particularly those with more severe seizures, are at risk of premature death. The contribution of deaths unrelated to epilepsy to this risk is likely to be significant. Recent studies indicate that comorbid conditions are similarly increased in PWE. The reason for these increases in unrelated deaths and comorbid conditions is unclear. In this article, we argue that having seizures is psychologically stressful, and that this stress can lead to a whole range of pathophysiological changes that may trigger various physical illnesses. Hence, psychological stress may be a significant factor contributing to the increase in mortality and comorbidity rates in PWE. This speculation is unlikely to be proven at this stage because of the complexity of the trials required. In PWE who continue to have seizures, more needs to be done to help them cope with the stress. Additionally, attention needs to be paid to improve nutritional status and physical fitness. These steps are likely to enhance the overall health of PWE and may reduce premature mortality and comorbidity rates.
  • Erythrocyte and plasma fatty acid profiles in patients with epilepsy: Does carbamazepine affect omega-3 fatty acid concentrations?

    Alan W.C. Yuen, Josemir W. Sander, Dominique Flugel, Philip N. Patsalos, Lucy Browning, Gail S. Bell, Matthias M. Koepp

    Epilepsy & Behavior.

    Fatty acids (FAs) determine membrane properties and may affect cardiac and neuronal function. In this study, FA profiles were determined in 56 patients with epilepsy who participated in a 12-week double-blind randomized trial of omega-3 FA supplementation (1 g eicosapentaenoic acid and 0.7 g docosah... [more] Fatty acids (FAs) determine membrane properties and may affect cardiac and neuronal function. In this study, FA profiles were determined in 56 patients with epilepsy who participated in a 12-week double-blind randomized trial of omega-3 FA supplementation (1 g eicosapentaenoic acid and 0.7 g docosahexaenoic acid daily). At baseline, subjects on carbamazepine (CBZ) had lower docosahexaenoic acid levels, lower levels of long-chain omega-3 FAs, and a lower Omega-3 Index (a risk factor for coronary heart disease mortality), whereas those on oxcarbazepine had higher total polyunsaturated FAs and a higher Omega-3 Index. Following omega-3 FA supplementation, the Omega-3 Index, eicosapentaenoic acid, and docosahexaenoic acid concentrations significantly increased. Patients on CBZ exhibited a less favorable FA profile, associated with a greater risk of coronary heart disease mortality. As arrhythmias are thought to be an important mechanism in coronary heart disease mortality and sudden unexplained death in epilepsy (SUDEP), the effect of CBZ effect in reducing omega-3 FAs might potentially explain some cases of SUDEP among patients prescribed CBZ.
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Publications