According to Sohlberg and Turkstra (2011) a plethora of acquired neurologic conditions that can produce both temporary and chronic cognitive impairment. Among these illnesses they identify conditions like anoxia, stroke or head trauma, where some recovery is expected, as well as progressive conditions in which a continuous deterioration can be anticipated as in Dementia and Multiple Sclerosis. These, and other chronic conditions affect individuals in various aspects of their lives such as social, emotional, vocational, as well as their families.
Chronic illness is defined as an adaptation process to significant in physical, psychological, social and environmental changes throughout life (Bishop, 2005). Gurung (2010) indicates that chronic illness can be progressive or remittent. In the case of Multiple Sclerosis, the condition is chronic and progressive and affects patients and their families. Even though there are pharmacological treatments, their effectiveness may vary and even cause other symptoms that hinder the individual’s abilities and quality of life. As an option, Curcuma longa (CL), Hypericum perforatum (HP), Ginkgo biloba (GB), Oethera biennis (OB) and Cannabis sativa (CS) are presented as adjuvant phytochemicals in the treatment of the condition.
Multiple Sclerosis is a recurrent, autoimmune, inflammatory, demyelinating, and neurodegenerative chronic disease that begins in young adulthood and is more common in females (Gumus, Akpinar, & Yilmaz, 2014). It is a complex and heterogeneous condition from the immunologic, neuropathological and clinical point of view, as well as the way it responds to different therapies (Varo-Sánchez, Cuenca-López, Fernández-Fernández, & Jordan, 2011). MS is characterized by diverse physical, neurocognitive and psychological symptoms. According to the Consortium of Multiple Sclerosis Centers (CMSC, 2010) MS has extensive and long-lasting effects affecting patients, families, and the community at large. Even though MS is one of the world’s most common neurologic disorders, and in many countries it is the leading cause of non-traumatic neurologic disability in young adults, in spite of global information on the epidemiology, the availability of resources and services for people with MS is scarce in many regions of the world (Browne, Chandraratna, Angood, Tremlett, Baker, Taylor, & Thompson, 2014). Medication is costly, the effect modest and health authorities are increasingly considering economics in the introduction of such treatments (Svendsen, Myhr, Nyland, & Aarseth, 2012).
Etiology and Epidemiology
Although the etiology of MS is still unknown (Oyama & Louro, 2005; Thorton & DeFreitas, 2009), there are different hypotheses about the origin of the condition that point to a close interrelation between predisposing genetic factors and environmental factors capable of triggering the autoimmune response at the central nervous system (Lagumersindez Denis, Oviedo Gálvez, & Martínez Sánchez, 2009). According to the Atlas of MS 2013: Mapping Multiple Sclerosis around the World published by the Multiple Sclerosis International Federation (MSIF, 2013): a) the estimated number of persons with MS increased from 2.1 million in 2008 to 2.3 million in 2013, b) MS is found in every region of the world with a ratio of 2:1 ratio of women to men, without significant changes since 2008, c) MS prevalence varies greatly, being highest in North America and Europe (140 and 108 per 100,000 respectively) and lowest in Sub-Saharan Africa and East Asia, at 2.1 and 2.2 per 100,000 respectively, and d) MS is usually diagnosed during early adulthood, with an average age of 30 years.
Classification of Disease Patterns and Symptoms
Given the unique nature of MS, its symptoms are varied and do not follow a specific pattern. According to the Consortium of Multiple Sclerosis Centers (CMSC, 2010) clinical characteristics include an unpredictable disease course of relapses, remissions, and progression of neurological disability.
MS is categorized into four different courses or subtypes:
- Relapsing-Remitting (RRMS)
- Secondary-Progressive (SPMS)
- Progressive-Relapsing (PRMS)
- Primary-Progressive (PPMS)
However, in order to work with this population accurate clinical course descriptions (phenotypes) of MS are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making (Lublin, Reingold, Cohen, Cutter, Sørensen, Thompson, et al., 2014). Therefore, revised guidelines by Lublin, et al. (2014) were published to better define MS types, including modifiers within those types. These include:
- Clinically isolate syndrome (CIS) – Active or not active
- Relapsing-remitting MS (RRMS) – Active or not active
- Primary-progressive MS (PPMS) – Active and with progression, Active but without progression, Not active but with progression, Not active and without progression (stable disease)
- Secondary-progressive MS (RRMS) – Active and with progression, active but without progression, not active but with progression, not active and without progression (stable disease)
With regard to the symptoms, Crespo-Bujosa (2014) indicates that among the most physical, neurocognitive and psychological symptoms of MS are:
- Fatigue and Weakness
- Mobility Problems
- Visual Problems
- Sexual problems
- Executive Functions
- Processing Speed
- Visuospatial Problems
- Adjustment Problems
Pharmacologic Treatment of MS
The complexity of MS involves many aspects of health including management of related or underlying issues, therefore requiring, considerable insight and judgment regarding appropriate services and treatment modalities that can adapt to the ever-changing needs of the patient (CMSC, 2010). On the economic aspect of MS treatment, Owens (2016) indicates that recent data suggest that out-of-pocket costs for 3 sample MS agents range from $5979 to $6448 annually. He adds that for the 3 MS drugs studied, an average of 34.7% of out-of-pocket costs were incurred by Medicare Part D enrolees after their spending reached the catastrophic coverage phase of the Part D benefit.
At present there is a variety of drugs used to modify MS including interferon beta (IFN-β), natalizumab, glatiramer acetate, alemtuzumab, fingolimod, teriflunomide, and dimethyl fumarate (Mahmoudian Sani, Asadi-Samani, Rouhi-Boroujeni, & Banitalebi-Dehkordi, 2016). According to Costello, Halper, Kalb, Skutnik and Rapp (2017), at present there are 15 medications are FDA-approved to treat MS, with ten (10) different mechanisms of action intended to address distinct components of the immune-mediated disease process. They add that:
- Treatments differ in:
- their route and frequency of administration
- their side effect and risk profiles
- Treatments are not curative
- The efficacy of any given medication varies considerably from one individual to another and for any given individual at different points in time.
- People with MS differ in their tolerance for:
- different routes of administration
- side effects
- Both clinicians and patients vary in their tolerance for risk, with risk tolerance likely undergoing shifts as the disease progresses.
For those reasons, access to the full range of options is essential in order to optimize the ability of people with MS and their clinicians to make optimal treatment decisions (Costello, Halper, Kalb, Skutnik, & Rapp, 2017). In addition treatment for many neuropsychiatric and neurodegenerative disorders with prolonged administration of synthetic drugs will lead to severe side effects (Phani, Anilakumar and Naveen (2015). Therefore, this serves as basis to open the spectrum of options to include phytochemicals which are at the very foundation of Complementary and Alternative Medicine.
Complementary and Alternative Medicine in the Treatment of MS
According to the World Health Organization (WHO) or Organización Mundial de la Salud (OMS, 2008) in Spanish, the alternative or complementary methods for the treatment of Multiple Sclerosis in more than 50% of the countries that participated on their study are:
- Diet and nutrition 88.3%
- Acupuncture 86.7%
- Herbal Medicine 81.7%
- Massage 78.3%
- Homeopathy 73.3%
Other methods reported were:
- Chiropractic and osteopathy 41.7%
- Aromatherapies 40%
- Hyperbaric Oxygenation 40%
- Cannabis 38.3%
- Ayurveda 36.7%
- Pilates 36.7%
- Dentistry 36.7%
- Biofeedback 35%
- Macrobioitic 31.7%
- Naturopathy 28.3%
- Hipnotherapy 21.7%
- Iridiology 18.3%
As shown above, there are many alternative and complementary modalities of treatment used worldwide by individuals with MS. In this matter diet and nutrition, and herbal medicine were the first and the third most used respectively demonstrating that they are seriously been implemented in treating the condition and regain health and wellbeing. This should serve as an invitation to look at Mother Nature for nourishment and health.
Complementary and alternative medicine involves the use of herbs and medicinal plants as an alternative to conventional western medical treatment (Sethi & Singh, 2015). In addition, nutritional neuroscience grows fast, and phytochemicals compounds such as curcumin, resveratrol, propolis, ginsenoside, and polyunsaturated fatty acids (PUFAs) have been extensively applied to potential therapeutic purposes for many neurodegenerative diseases due to their anti-oxidative and anti-inflammatory effects (Wang, Song, Gao, Bai, & Chen, 2016). Since MS is a heterogeneous autoimmune, inflammatory neurologic condition, the implementation of various phytochemicals should be seriously considered, especially those that scientific literature has shown to be effective in reducing inflammation and mood and promoting neuroprotection.
The following phytochemicals have been associated with these aspects.
- Curcuma longa. Curcumin has traditionally been used for wound healing and to treat inflammatory disorders (Mahmoudian Sani, Asadi-Samani, Rouhi-Boroujeni, & Banitalebi-Dehkordi, 2016). Curcuminoids, as the main polyphenol constituents of CL, comprise three chemical components: curcumin (75%–80%), demethoxycurcumin (15%–20%), and bisdemethoxycurcumin (3%–5%) (Wang, et al., 2016). According to Nabiuni, Nazari, Angaji, and Nejad (2011), a number of experimental studies indicate that Curcumin, as an antioxidant protects the brain against various oxidative stressors, acting as a powerful hunter of superoxide anions, and it has neuroprotective and anti-aging effects. They add that it can cross the blood-brain barrier and reach the brain. Finally they point out that the accumulating cell culture and animal model data show that dietary Curcumin is a strong candidate for use in the prevention or treatment of Neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis, Ischemic cerebral stroke, epilepsy and depression.
- Hypericum perforatum or St. John’s wort. It is a plant from the Hypericaceae family, and is used in traditional medicine for treatment of mild to moderate depression, and has also been used as an antioxidant, anti-inflammatory and wound healing agent (Mahmoudian Sani, et al., 2016). The data pertaining HP’s efficacy in depression goes back to the writings of Hippocrates (Gromova, 2013). The phytochemical profile of HP consists of several groups including phenolic acids (chlorogenic acid), flavonoids (rutin, hyperoside, isoquercitrin, quercitrin, quercetin), napthodianthrones (hypericin, pseudohypericin), and the phloroglucinols (hyperforin, adhyperforin) (Asadian, Rahnavard, Pourshamsian, Ghorbanpour, & Taghavi, 2011). The therapeutic potentials of an Hypericum Perforatum extract (HPE) and a single component, hyperforin were evaluated for effectiveness against MOG35–55-induced experimental autoimmune encephalomyelitis (EAE), an animal model for human MS on a research conducted by Nosratabadi, Rastin, Sankian, Haghmorad, Tabasi, Zamani, Aghaee, et al., (2016). The effect of hyperforin on regulatory T-cells (Treg cells) was assessed using flow cytometry, and the results showed hyperforin and HPE reduced the incidence and severity of EAE, an outcome that closely correlated with an inhibition of pathological features (leukocyte infiltration and demyelination) and antigen-specific T-cell proliferation. Their study also revealed that hyperforin caused increased Treg cell levels in the spleen indicating that hyperforin and HPE could attenuate EAE autoimmune responses by inhibiting immune cell infiltration and expansion of Treg cell and could eventually be considered as a potential candidate for use in the treatment of MS.Oenothera biennis or Evening Primrose. The plant parts that are used are seeds, seed oil, leaves, and roots (David, Niţă, & Borcean, 2009). Rezapour-Firouzi, Arefhosseini, Farhoudi, Ebrahimi-Mamaghani, Rashidi, Torbati, and Baradaran (2013) carried out a study to examine the correlations between Expanded Disability Status Scale (EDSS) and cytokines after intervention with co-supplemented hemp (Cannabis sativa) seed and evening primrose (Oenothera biennis) oils and hot-natured diet in 23 patients with relapsing-remitting (RR) MS. Clinically EDSS and immunological factors (plasma cytokines of IL-4, IFN-γ and IL-17) were assessed at baseline and after 6 months. After 6 months, significant improvements.
- Ginkgo Biloba has demonstrated antioxidant and vasoactive properties as well as clinical benefits in several conditions such as epilepsy, ischemia, and peripheral nerve damage (Brondino, De Silvestri, Re, Lanati, Thiemann, Verna, Emanuele, et al., 2013). EGb 761 is a well-defined mixture of active compounds from GB that contains two (2) main active substances: flavonoid glycosides (24–26%) and terpene lactones (6–8%) that have shown antiapoptotic effects through the protection of mitochondrial membrane integrity, inhibition of mitochondrial cytochrome c release, enhancement of antiapoptotic protein transcription, and reduction of caspase transcription and DNA fragmentation (Serrano-García, Pedraza-Chaverri, Mares-Sámano, Orozco-Ibarra, Cruz-Salgado, Jiménez-Anguiano, Sotelo, et al., 2013). Johnson, Diamond, Rausch, Kaufman, Shiflett, and Graves (2006) carried out a study that used a double-blind, placebo-controlled, parallel group design to identify changes between baseline (ie, preintervention) and follow-up evaluation following a regimen of four (4) tablets per day at 60 mg of GB extract (EGb 761), per tablet for four weeks. The results showed that the GB group had significantly more individuals showing improvement on four (4) or more measures with improvements associated with significantly larger effect sizes on measures of fatigue, symptom severity, and functionality, and also showed less fatigue at follow-up compared with the placebo group.
- Oenothera biennis or Evening Primrose. The plant parts that are used are seeds, seed oil, leaves, and roots (David, Niţă, & Borcean, 2009). Rezapour-Firouzi, Arefhosseini, Farhoudi, Ebrahimi-Mamaghani, Rashidi, Torbati, and Baradaran (2013) carried out a study to examine the correlations between Expanded Disability Status Scale (EDSS) and cytokines after intervention with co-supplemented hemp (Cannabis sativa) seed and evening primrose (Oenothera biennis) oils and hot-natured diet in 23 patients with relapsing-remitting (RR) MS. Clinically EDSS and immunological factors (plasma cytokines of IL-4, IFN-γ and IL-17) were assessed at baseline and after 6 months. After 6 months, significant improvements in extended disability status score were found in the patients in agreement with decrease cytokines of IFN-γ and IL-17 and increase cytokines of IL-4.
- Cannabis, Hemp or Marijuana. Hemp (Cannabis sativa L.) is an annual species, native of central Asia, is the source of hundreds of biological active compounds such as cannabinoids, terpenoids, flavonoids and polyunsaturated fatty acids (Piccaglia, Grandi, Zatta, & Amaducci, 2005). According to Lakhan and Rowland (2009) combined Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts may provide therapeutic benefit for MS spasticity symptoms. On a placebo-controlled, crossover trial involving adult patients with multiple sclerosis and spasticity conducted by Corey-Bloom, Wolfson, Gamst, Jin, Marcotte, Bentley, and Gouaux (2012), 30 participants completed the trial where they were treated with smoked Cannabis and resulted in a reduction in patient scores on the modified Ashworth scale by an average of 2.74 points more than placebo (p < 0.0001). Also pain scores reduced on a visual analogue scale by an average of 5.28 points more than placebo (p = 0.008). However, scores for the timed walk did not differ significantly between treatment and placebo (p = 0.2). Scores on the Paced Auditory Serial Addition Test decreased by 8.67 points more with treatment than with placebo (p = 0.003). Some acute cognitive effects were also evidenced from smoked Cannabis.
Nutrition is key to provide the body with the adequate sources of energy to re-establish proper functioning and reduce symptom recurrence and progression of the condition. An adequate nutritional intake in addition to phytochemicals serves as a continuous treatment to individuals with Multiple Sclerosis and other conditions. Furthermore, phytochemicals and nootropics are vital cofactors with powerful effects on the body helping it regain functionality. As it has been shown even though phytochemicals may have different mechanisms of action and different levels of effect in the body, there are overlapping aspects such as antioxidant, anti-inflammatory, and corrective effects that produce physical, cognitive and even positive mood changes in the individual with Multiple Sclerosis.
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