Title: The advisability of dietary changes in the prevention and treatment of neurodegenerative disease
Key words: neurodegenerative, pathogenesis, Parkinson’s, disease, Alzheimer’s, motor neurone, Huntingdon’s, multiple sclerosis, free radical, nervous system, ageing, oxidizable stress, aetiology, Alzheimer’s plaques, vitamin C, vitamin E, vitamin B12, curcumin, turmeric, ferulic acid, whey proteins, vitamin B1, resveratrol, ginkgo biloba, lipoic acid, glutathione, plant polyphenols, green tea, cognitive, neurological, atherosclerosis, dietary interventions,
Date: Sept 2006
Category: Specific conditions, Special diets
Author: Morgan, G
The advisability of dietary changes in the prevention and treatment of neurodegenerative disease
Oxidative damage coupled with the non-regenerative nature of neuronal tissue are thought to be major factors in the pathogenesis of the neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, motor neurone disease, Huntingdon’s disease and multiple sclerosis (Smith 1996, Halliwell 1999). The high oxygen turnover of the nervous system, the presence of substantial polyunsaturated fatty acids, the availability of redox-active transition metal ions and the limited anti-oxidant status of nervous system help to promote such free radical damage (Butterfield 2002).
Aging itself is associated with diminishing antioxidant status, a process mirrored for example in Alzheimer’s disease where low plasma levels of vitamins B, C and E, folate and glutathione reflect the severity of the illness (Youdim 2001, Nourhashemi 2000). This has led to the ‘oxidizable stress’ hypothesis (Markesbery 1997, Butterfield 2001) for the aetiology of this disease. Oxidizable stress has also been shown to operate in Parkinson’s disease (Pileblad 1988, Spencer 1995), motor neurone disease (Tu 1997), and multiple sclerosis (Bagasra 1995).
The corollary to this hypothesis is that, as with cardiovascular disease, increased antioxidant status should help to prevent further free radical damage and reduce the incidence of these diseases. Research has shown that specific pathological lesions serve as foci and catalysts for further free radical damage. Alzheimer’s plaques, for example, are known to be intensely neurotoxic (Selkoe 1994). No research to date has demonstrated the ability of any therapy to promote regression of these lesions. The efficacy of antioxidant strategies has therefore focused on the prevention of further disease progression. Most research has concentrated on Parkinson’s and Alzheimer’s disease. T
The interlocking nature of antioxidant defence systems indicates that individual antioxidants are often dependent on other antioxidants for their regeneration. The relation between vitamin C, vitamin E, lipoic acid and glutathione is of this order (Buettner 1993). Only a few studies (Chandra 2001,Kontush 2001) have looked at the efficacy of giving two or more vitamins and minerals to improve cognitive or neurological performance – with positive results. The frequent inability to demonstrate beneficial effects with single antioxidants needs to be interpreted in this light.
With respect to Alzheimer’s disease, laboratory research has confirmed antioxidant protective effects for the plant polyphenols (Ishige 2001), curcumin (Kuner 1998), ferulic acid (Kanski 2002) and the whey proteins (Tong 2000). Intervention trials have been conducted with vitamins B1, B12, C, E, lipoic acid, resveratrol (in red grapes) and gingko biloba with evidence of cognitive improvement (Meador 1993, Nilsson 2000, Kontush 2001, Hager 2001, Orgogozo 1997, Le Bars 1997). Some researchers (Ganguli 2000) attribute the low incidence of Alzheimer’s in the Indian subcontinent to the high intake of curcumin (turmeric) in that region.
With Parkinson’s disease, dietary interventions have shown less beneficial results though the polyphenols present in green tea (epigallocatechin gallate) appears to offer some protective effect (Hellenbrand 1996). Dietary intervention studies are difficult to interpret. The results of a vitamin E trial (Sano 1997), for example, which showed an up to 6 month delay in the admission of Alzheimer’s patients to institutional care when given 2000 i.u of vitamin E per day, have been interpreted as showing a design flaw rather than a therapeutic effect (Pincus 1997).
Combinations of antioxidants may, as mentioned, be more highly powered statistically to demonstrate an effect. In general, the results of in vivo trials confirm the theoretical basis for the use of antioxidants in neurodegenerative disease, particularly in Alzheimer’s disease, even if the effects are modest. As with atherosclerosis, a lifetime’s exposure to plant polyphenols, present in fresh fruit and vegetables, red wine and green tea, appear to offer the greatest prophylactic help. In the earlier stages of Alzheimer’s, supplements such as vitamins C and E, curcumin and gingko biloba appear to improve cognitive function and delay the onset of incapacitating Alzheimer’s.
Dietary interventions appear to offer some benefit in this disease area but further large trials need to be done looking at the efficacy of earlier interventions especially with combinations of antioxidants.
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