Dr. Frans J. Cronjé


  MBChB  (UP), MSc






FJ Cronje 1, SJ van Rensburg 2, MJ Kotze 3

1 Interdisciplinary Medicine, Stellenbosch University, Cape Town, South Africa Chemical Pathology, NHLS and Stellenbosch University, Cape Town, South Africa

2  Division of Chemical Pathology, Department of Pathology, NHLS and Stellenbosch University, Cape Town, South Africa

3  Division of Anatomical Pathology, Department of Pathology, Stellenbosch University, Cape Town, South Africa




Multiple sclerosis (MS) is a chronic neurodegenerative and demyelinating disease of the central nervous system [1]. It affects approximately 5-30 per 100,000 of the population in medium frequency countries, including South Africa, with a prevalence rate of 1 per 700 [2]. Based on 2006 data, at least 63,497 people are suffering from MS in South Africa [2]. 


MS remains surrounded by controversy and scientific contradiction [3-5]. Histopathological evidence remains inconclusive on whether MS is primarily an autoimmune inflammation or a primary loss of oligodendrocytes with a secondary inflammatory response [6,7]. Puzzling aetiology, divergent risk factors, diagnostic uncertainty and a variable clinical progression continue to plague consensus on diagnosis and management [5, 8-11].


Four clinically defined sub-types of MS are recognised: Relapsing-remitting (RRMS), Secondary Progressive (SPMS); Primary Progressive (PPMS) and Progressive Relapsing Multiple Sclerosis (RPMS). The category of Benign MS is assigned retrospectively in the absence of disease progression over 10 to 15 years [12]. In a recent survey of 430 South Africans with MS, 46% had RRMS, 13 % SPMS, and 12% PPMS [2].


Present Treatment Paradigms and their limitations


Since Charcot’s first description of post mortem sclerosing plaques and a clinical triad of nystagmus, intention tremor, and scanning speech (dysarthria) in 1868 [13], MS has been the target of a vast variety of treatments [14]. Scientific evidence largely supports the use of disease modifying drugs (DMD’s) for RRMS although a recent well-conducted RCT has challenged the long-term benefits of Interferon beta [15-21]. The rationale behind the use of DMD’s lies in their ability to alter or desensitise presumed T- and B-cell-directed destruction of myelin or cytotoxicity related to activated microglia [27]. DMD’s are costly, however, and some require regular injections [25]. Patient education may improve DMD compliance, but lack of medical insurance or denial of coverage for DMD’s often present insurmountable barriers to their use. Also, DMD’s do not work for everyone [28, 29]. For instance, between 20 to 55% of patients with RRMS do not respond to Interferon beta [30-32].  Unpleasant side-effects are common and MS symptoms may even be exacerbated [21, 31-35]. Lowered relapse rates do not assure the absence of disease progression nor does it predict the level of ultimate debilitation [36, 37]. The prescription of DMD’s is therefore complicated and actual utilization figures bear this out: In a South African survey, DMD’s were not used by 32% of respondents; 30% were on methotrexate; and only 22% on interferon beta [2].


The choice of whether or not to use DMD’s is not the only challenge that patients face: The diagnosis of MS is often inconclusive following the first clinical episode of acute demyelination [38].  Given the gravity and implications of making the diagnosis, doctors frequently delay pronouncing it [39, 40]. Isolated radiological findings, although suggestive of MS, are not necessarily pathognomonic and are not treated in the absence of clinical manifestations [41]. The net result, not infrequently, is an indefinite period of uncertainty without any specific intervention [39, 42, 43]. During this time patients frequently pursue complementary and alternative medicine (CAM) with or without their health care provider’s involvement or consent [44-47]. Unless this dynamic is understood and accommodated in the overall care of the MS patient, patient-doctor relationships may suffer [48]. Ignorance, discomfort, lack of confidence or prejudice towards CAM may manifest in the form of a generalised criticism of all non-pharmacological therapies or an insistence on DMD’s even when these are not indicated. Unspoken fatalism towards the presumed autoimmune nature of the disease may also discourage the HCP from motivating patients to play an active role in preserving their health [49]. Worse still, HCP’s may even actively dissuade patients from appropriate exercise or nutrition by expressing unsubstantiated concerns that these may aggravate or provoke MS relapses. All this ambiguity and uncertainty often leaves patients stranded in a “no man’s land” where DMD’s are not an option and all other possibilities are not encouraged or even dismissed.


Personalizing Medical Advice in MS:


The indications for DMD’s fall outside the scope of this article and are usually determined by a neurologist [50-52]. However, there is more to managing MS than preventing demyelination by means of immunosuppression [48]. Interventions may be indicated to address fatigue, occupational disability, mental health co-morbidities, pain and altered body image concerns [53-58]. MS patients typically favour remedies that are pragmatic to offset the feelings of helplessness [59, 60].  In this setting, HCP’s may find it quite challenging to come up evidence-based, economically viable and practical health recommendations that are also meaningful to the patient [60].


Whilst by no means exhaustive, there are at least four areas that offer opportunities for pro-active discussions. They are also relevant at any stage of the disease, whether or not patients are on concurrent DMD’s:


  • Remaining physically & mentally active:

Demyelination is not the only pathophysiological feature of MS [61]. Direct axonal and neuronal damage appears to continue even between relapses [62]. This gradual deterioration eludes conventional neuro-imaging surveillance which usually focuses primarily on the inflammatory and sclerotic components of the disease [63, 64]. So the “white spots on the MRI” are not the whole story [65]. In fact it appears to be the “invisible” neurodegenerative components that determine the ultimate physical and mental disability [66]. As such, strategies for preserving cognitive function, preventing social isolation and optimising physical health are important and should be encouraged actively while avoiding fatigue and overexertion [67-69]. 


  • Support myelin maintenance & repair:

Myelin is synthesised and repaired on an ongoing basis [70].  Oligodendrocyte precursors (adult stem cells that are normally present in the brain) are able to replace damaged myelin [71]. However, MS patients have a higher turnover of glia and myelin and this imposes increased nutritional demands on repair mechanisms [72]. Not surprisingly, MS patients often develop deficiencies [46, 73-76]; these include iron, all the components of the folate-vitamin B12-methionine methylation system, vitamin D, essential amino acids and essential (unsaturated) fatty acids [77, 78]. These deficiencies are rarely appreciated or addressed, even though readily reversible. Importantly, consistent availability of all these components is a prerequisite for optional myelin synthesis and repair [46, 73-76]. Therefore, regular dietary intake is essential to meet increased demands and becomes critical during MS relapses. Clinical improvements have been recorded in MS patients following a specific supplementation regimen [76].  Such supplementation may also be associated with improved cognitive function and preservation of brain volume in normal individuals [79, 80]. Whilst patient-selected arbitrary supplementation is quite common, formal assessment may better differentiate patients who need individualised iron, Vit B12 and Vit D supplementation [81, 82]. When nutritional strategies are based on objective assessments (biochemical tests), they are generally adopted with greater confidence and commitment [61].


  • Avoid toxic & oxidative stress – e.g., assisting patients to avoid exposure to cigarette smoke:

Oligodendrocytes and their precursors are vulnerable to reactive oxygen species, excitotoxicity and hypoxia [83]. Lipid peroxidation by free radicals plays a large role in myelin damage [84, 22]. As such, lifestyle choices have the potential to impact MS [85]. Avoiding external toxicities and supporting the body’s various detoxification and antioxidant strategies are appropriate. These include glutathione, copper-zinc and manganese superoxide dismutase (CuZnSOD / MnSOD), catalase (containing iron) and glutathione peroxidase (containing selenium), as well as the antioxidant vitamins (e.g., Vit C, Vit E and beta carotene). In addition, avoiding active or passive smoking, moderate alcohol intake and appropriate exercise are all important considerations. As with nutrition, the greatest challenge lies in motivating patients to want to make the change and to take responsibility for their health [86]. Therefore, the HCP’s attitude towards promoting health preservation is essential for patient commitment. In our experience health messages that promote “preserving the body’s ability for self-renewal” are more motivating than those that propose “doing what you can to delay the inevitable”.


  • Pathology Supported Genetic Testing:

MS patients have a number of potential genetic risk factors [87]. Whilst not correctable at our present state of knowledge or technology [88], several important enzyme-related single nucleotide polymorphisms (SNP’s) can be addressed indirectly through lifestyle and nutritional interventions: Focused genetic testing may identify these SNP’s and offer various enzyme supporting, enhancing or regenerating strategies [89-91]. Again, objective information adds confidence and promotes a greater willingness to participate [92]. Patient motivation is critical for success. Therefore, any proposed recommendations should be realistic and verifiable [93]. Linking small and simple lifestyle changes to a patient’s present routines is often more effective than trying to implement radical changes or complicated regimens [94, 95].


Explaining the value of lifestyle choices and nutritional support for MS


MS is a complex disease. Given the controversy still surrounding the use of DMD’s after decades of rigorous and well-funded research, it is improbable that a clear answer will emerge on the impact of various dietary interventions or nutritional supplements on disease progression [23]. Basic biochemistry testing can assist in determining those factors that are in greatest need of intervention and then to build sound lifestyle recommendations around maintaining them at optimal levels. There are also many resources to assist in communicating the value of better lifestyle choices with patients. Although many would be considered basic common sense, these small, simple, practical and beneficial choices should be encouraged actively [96].




Multiple sclerosis is a prevalent and devastating disease. Pharmacological interventions are indicated during relapses and in certain forms of the disease. However, many patients fall outside of the criteria for specific intervention. For these individuals in particular, the assessment of specific and modifiable lifestyle, biochemical and genetic risk factors may offer an objective, personalised and practical way to lower their risk for deterioration and to support the ongoing synthesis, maintenance and repair of myelin. The authors hope that this article will assist in motivating and equipping primary HCP’s and their patients alike to play a more active role in preserving health.





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