The Rapha Regimen Program

Your Body Needs a Healthy Brain

Rapha Regimen is a range of
supplements we brought to life
after Prof Susan JV Rensburg
and Prof MJ Kotze discovered
deficiencies in MS patients.

These deficiencies ranged
from low ferritin iron levels
to vitamin deficiencies, and
a lack exercise. Once these
were addressed, patients saw
positive health outcomes.

Rapha Regimen is safe to be
used as a daily multi-vitamin
by any age group to ensure the
brain has a sufficient supply
of vital nutrients like Omega 3.

Professor Susan JV Rensburg is
currently helping patients with
the Rapha Regimen program.

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The Research

Pathology-supported genetic testing presents opportunities for improved disability outcomes in multiple sclerosis.

Abstract

Background: Lipid metabolism may impact disability in people with multiple sclerosis (pwMS). Methods: Fifty-one pwMS entered an ultrasound and MRI study, of whom 19 had followed a pathology-supported genetic testing program for more than 10 years (pwMS-ON). Genetic variation, blood biochemistry, vascular blood flow velocities, diet and exercise were investigated. Results: pwMS-ON had significantly lower (p < 0.01) disability (Expanded Disability Status Scale) than pwMS not on the program (1.91 ± 0.75 vs 3.87 ± 2.32). A genetic variant in the lipid transporter FABP2 gene (rs1799883; 2445G>A, A54T) was significantly associated (p < 0.01) with disability in pwMS not on the program, but not in pwMS-ON (p = 0.88). Vascular blood flow velocities were lower in the presence of the A-allele. Conclusion: Pathology-supported genetic testing may provide guidance for lifestyle interventions with a significant impact on improved disability in pwMS.

Plain language summary

This study investigated the role of a genetic variant that increases saturated fat absorption and may make people with multiple sclerosis (MS) more susceptible to disability progression. Of 51 people with MS, 19 had followed a program which includes normalization of blood test results and daily intake of unsaturated fatty acids for more than 10 years, while the others had not. The latter group had significantly greater disability than the people who had followed the program, suggesting that the unsaturated fatty acids modulated the effect of the genetic variant. Six MS cases are presented as examples, including a marathon athlete (Case 1) and a patient who showed a dramatic decrease in disability from being wheelchair-bound for 15 years to walking freely (Case 2).

pubmed.ncbi.nlm.nih.gov/37194915/

Case Study 1

A 21-year old female was diagnosed with MS in 2006. She reported a paternal family history of hemochromatosis, heart disease and type II diabetes mellitus, and a maternal family history of breast cancer and ulcerative colitis. Blood investigations revealed nonanemic iron deficiency (low serum iron with normal hemoglobin and ferritin levels). Genetic analysis indicated heterozygosity for the iron-loading HFE C282Y variant. Additional genetic testing 8 years thereafter demonstrated co-occurrence of the iron-lowering missense variant TMPRSS6 A736V in the homozygous state. The dietary study questionnaire at the time revealed high intake of saturated/trans fat and a low intake of fruits/vegetables. Her BMI was 27.4 kg/m2 (slightly overweight). She was commenced on the Rapha Regimen which resulted in normalization of her iron status. Neurological examination 3 years later revealed abnormal deep tendon reflexes on the right side with motor disability (EDSS 1.5). Biochemical analysis identified very low vitamin D levels, suboptimal serum folate levels and high normal vitamin B12. Her BMI had increased to 29 kg/m2. Then, 4 years after the initial presentation, she again experienced right-sided upper and lower limb weakness which resulted in poor coordination and balance, and pain in her right leg and back. Interventions included a short course of intravenous pulsed corticosteroids and continuation with the Rapha Regimen, as well as physical rehabilitation.Thereafter, 2 years later and 6 years after the initial presentation, she experienced visual disturbances. No disease-modifying agents were prescribed. Instead, the patient opted for lifestyle changes that included increased fruit/vegetable intake, exclusion of fast foods and regular aerobic exercises (park runs followed by marathons). Over time this led to normalization of her BMI to 21.9 kg/m2. Her EDSS remained stable at 1.5.

After another 8 years, she developed lower limb pain/weakness, back pain and speech problems, 3 weeks after recovery from COVID-19 infection. Formal ophthalmology examination proved normal. The patient was pulsed with intravenous methylprednisolone and also required amitriptyline for neuropathic pain. She experienced myelopathy most likely related to SARS-CoV-2 infection (postinfectious autoimmune demyelination). Her blood tests proved normal. The response to neurorehabilitation with the Rapha Regimen proved favorable, the neuropathic pain resolved and she was able to resume long distance running again. Her EDSS was noted as 2.0, which is within the benign range as evidenced by her ability to complete several marathons and an ultramarathon. After following the PSGT Program together with the Rapha Regimen, she has remained in good health and participates in Ultramarathons. She has to be followed up regularly for low iron blood levels. 

Care Study 2

After diagnosis with MS at age 31, a lady was confined to a wheelchair within 2 years. Some 14 years after MS diagnosis, she voluntary enrolled in our institution’s first MS research study, which aimed to study the genetic underpinning of iron dysfunction in MS. [3]. Although she was heterozygous for the iron-loading C282Y missense variant in the HFE gene, her iron levels were very low, and she was advised to take iron supplements. Possible iron deficiency risk factors included untreated childhood iron deficiency anemia, frequent blood donations and two pregnancies. After starting iron supplementation, she improved sufficiently to start teaching again, but remained wheelchair dependent and used a scooter. Gastrointestinal adverse effects led to cessation of iron supplementation. Ten years later she enrolled in a second MS substudy which entailed PSGT. At the time she was wheelchair-dependent and biochemical testing revealed severe iron deficiency anemia (ferritin 3 μg/l, transferrin saturation 4% and hemoglobin 10.7 g/dL). The study diet questionnaire noted high saturated fat intake and very low fruit and vegetable intake. Regular follow-up ensued to ensure iron supplementation compliance as part of the Rapha Regimen supplementation program. In addition to dietary modifications, evening primrose oil (500 mg daily) was prescribed. Rehabilitation efforts coupled with PSGT guidance led to supported walking after 2 years and unsupported walking for almost 300 m two years thereafter. Biochemical testing revealed normal serum iron levels despite low ferritin levels. Her EDDS score was 6.0, and 2 years later, her EDDS had improved to 2.0 (minimal disability in one functional system) with normalization of all iron blood parameters. She has now been able to leave the scooter and can walk normally.

Care Study 3

A young female experienced her first episode of acute cerebral demyelination shortly after the birth of her first child at age 30. Her symptoms at the time of MRI diagnosis were loss of vision, disorientation and poor balance. Upon MS study enrollment shortly thereafter, blood investigations revealed a low ferritin (10 μg/l), low vitamin B12 (355 ng/l) and high fasting serum cholesterol (6.2 μg/l) levels. The study dietary questionnaire revealed a high saturated fat intake, a very low folate score, and suboptimal fruit and vegetable intake (consumption of
five fruits/vegetables only on 2 days per week). Previous medical history noted frequent episodes of migraine, anemia and recurrent fatigue. Remitting–relapsing MS was diagnosed when she experienced a first relapse (whole body paralysis) 6 months later. The EDDS score at the time was 1.5. Fortunately, the response to oral corticosteroids proved favorable. A second relapse occurred 4 years later when she presented with disorientation, blurred vision and loss of balance. Therapy at the time included corticosteroids. After 10 years of compliance to the PSGT guided program, including regular iron intake, her EDSS 1.5 has remained stable (no disability, minimal signs in more than one functional system). Lifestyle modifications implemented include a change to a moderate saturated fat intake, a higher folate score and daily intake of five fruits/vegetables.

Care Study 4

A young female with a longstanding history of fatigue and heat intolerance presented with left-sided focal motor weakness during anesthesia for a dental procedure at age 25. Subsequent neurological examination and diagnostic workup confirmed MS. Blood investigations during enrollment into the MS study 5 years later revealed iron deficiency state and hypercholesterolemia. Oral iron supplementation improved her iron status; however, further neurological exacerbations occurred following cessation of iron supplementation due to gastrointestinal adverse effects and gluten sensitivity. Risk factors for iron deficiency state included a long-standing history of fatigue, restless leg syndrome and multiple gestation pregnancies. Statin myopathy led to a vegan diet with omega-3 supplementation which resulted in a reduction in serum cholesterol from 8 μg/l to 6 μg/l. She never smoked and exercises daily. A total of 18 years after diagnosis, and 15 years after enrollment on the PSGT program, her EDSS remains at 1.5 (no disability, minimal signs in more than one functional system). She works as a music teacher. 

 

Care Study 5

A middle-aged female presented with slurred speech and loss of coordination at age 48. Previous medical history indicated that she required treatment for iron deficiency anemia on several occasions, especially following the birth of each of her four children. Neurological examination and diagnostic workup which included blood investigations, cerebrospinal fluid analysis and MRI suggested MS. Upon MS study enrollment 2 years later, her EDDS score was 1.0 and blood investigations revealed a low serum ferritin (13.6 μg/l). At the time her EDSS score was 1.5. A total of 2 years thereafter she experienced a minor relapse which required in hospital intravenous pulsed corticosteroid administration. No further relapses were encountered during the following 5 years and her EDDS score has remained static at 1.5. Frequent follow-up revealed normal iron and vitamin B12 status due to nutritional supplementation. At present she is healthy and works full-time as a teacher.

Care Study 6

A middle-aged female presented with paralysis of her left arm, paresthesias in her right leg, vision disturbance and seizures at age 45. Previous medical history, neurological examination and diagnostic workup which included blood investigations, cerebrospinal fluid analysis and MRI suggested MS. Treatment at the time consisted of corticosteroids and later on IFN-ß. Upon enrollment into the MS research study 1 year later, she was noted to have iron deficiency anemia (hemoglobin 11.9 g/dl, serum iron 10.3 μmol/l, transferrin saturation 18%, ferritin 41 μg/l) with low serum cholesterol. Dietary history revealed a low level of fat intake, high intake of fruits and vegetables with omega-3, -6 and vitamin B (neurobion) supplementation. Her EDSS score prior to enrollment was 4.0. Then, 4 years after enrollment she experienced a neurological relapse following insecticide exposure (cockroach spray) which warranted a short course of corticosteroids. After 15 years of compliance to the PSGT program, her EDDS had improved and has remained 3.0 with normal blood biochemical. She remains in excellent health and is full-time employed.

Pathology Supported Genetic Testing

demyelinating diseases genescreen

A multiplex DNA test which analyses a combination of genetic variants in individuals previously diagnosed with demyelinating diseases such as multiple sclerosis (MS). The results are interpreted in the context of blood biochemistry (pathology), family history and lifestyle factors such as diet composition and smoking. 

This is our 3 pronged approach called Pathology Supported Genetic Testing (PSGT).

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Here’s another article on
the importance of iron.

The PSGT Program

The PSGT Program evaluates the risk factors for MS in every specific individual. 

 

The reason(s) for MS disability have been the ongoing subject of a research study approved by the University of Stellenbosch Ethics Committee in 1996 [1, 28]. This has involved pathology-supported genetic testing (PSGT) to search for genetic and environmental risk factors for demyelination [24, 25]. Following a study that recruited 118 pwMS to investigate the role of iron in MS [4], subsequent sub-studies found that risk factors for MS diagnosis and progression fall into two categories: (1) deficiencies: (iron, vitamin D, vitamin B12, antioxidants, unsaturated oils, decreased CNS blood flow) and (2) aggravators: (oxidation/inflammation, smoking, dietary saturated fat, increased cholesterol/homocysteine/obesity; infections, allergies/food sensitivity and psychological stress). The rationale was outlined previously [24, 25, 28]. 

 

Since pwMS are not all affected similarly, people are offered the opportunity to enrol at Genecare in a PSGT Program that allows assessment of their personal risk factors and optimization of cerebral nutrients. The Program entails performance of biochemical tests that allow for the identification of possible deficiencies of iron, vitamin D and vitamin B12, or excess cholesterol/homocysteine ratios and increased inflammation (CRP). This is complemented by genetic testing aimed at identification of clinically relevant variants in metabolic pathways and integration thereof with family history, biochemistry and lifestyle data to generate personalized reports [18, 28].  These reports enable clinicians to address imbalances revealed in the blood test investigations so that all the biochemical risk factors are mitigated through nutritional supplementation and modification of diet. In addition, the provided reports address lifestyle risks such as smoking and lack of exercise which potentially impair cerebral circulation, which is vital  for adequate delivery of oxygen and nutrients to the oligodendrocytes [27, 29]. Details about the PSGT program and its beneficial effects have been comprehensively described in several publications [24, 25, 28].



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REFERENCES 

  1. Rooney RN, Kotze MJ, de Villiers JN, et al. Multiple sclerosis, porphyria-like symptoms, and a history of iron deficiency anemia in a family of Scottish descent. Am J Med Genet 1999; 86(2): 194-196. PMID: 10449660 DOI: 10.1002/(sici)1096-8628(19990910)86:2<194::aid-ajmg21>3.0.co;2-c
  2. Van Rensburg SJ, Kotze MJ, Hon D, Haug P, Kuyler J, Hendricks M, Botha J, Potocnik FCV, Matsha T and Erasmus R. 2006. Iron and the Folate-Vitamin B12-Methylation Pathway in Multiple Sclerosis. Metabolic Brain Disease 21:121-137. PMID: 16729250 DOI: 10.1007/s11011-006-9019-0
  3. De Villiers JNP, Treurnicht FK, Warnich L, Carr J, van Rensburg SJ and Kotze MJ. 2006. Analysis of viral and genetic factors in South African patients with multiple sclerosis. Metabolic Brain Disease 21:163-169. PMID: 16865539 DOI: 10.1007/s11011-006-9016-3
  4. Kotze MJ, de Villiers JNP, Warnich L, Schmidt S, Carr J, Mansvelt E, Fourie E, Van Rensburg SJ. 2006. Lack of clinical manifestation of hereditary haemochromatosis in South African patients with multiple sclerosis. Metabolic Brain Disease 21:109-120. PMID: 16850257 DOI: 10.1007/s11011-006-9015-4
  5. Hon, G.M, Hassan, M., van Rensburg, S., Abel, S., Marais, D., van Jaarsveld, P., Smuts, C., Henning, F., Erasmus, R., Matsha, T. 2009. Erythrocyte membrane fatty acids in patients with multiple sclerosis. Mult Scler, 15:759-762. PMID: 19435752 DOI: 10.1177/1352458509103321
  6. Hon, G.M, Hassan, M., van Rensburg, S.J., Abel, S., Marais, D.W., van Jaarsveld, P., Smuts, C., Henning, F., Erasmus, R., Matsha, T. 2009. Immune cell membrane fatty acids and inflammatory marker, C-reactive protein, in patients with multiple sclerosis. Br J Nutr, 19:1-7. PMID: 19454128 DOI: 10.1017/S0007114509382185
  7. Hon GM, Hassan MS, Janse van Rensburg S, Abel S, Erasmus RT and Matsha T. 2009. Membrane saturated fatty acids and disease progression in Multiple Sclerosis patients. Metab Brain Dis 24:561-568. PMID: 19890702 DOI: 10.1007/s11011-009-9159-0
  8. Hon GM, Hassan MS, Janse van Rensburg S, Abel S, Van Jaarsveld P, Erasmus RT and Matsha T. 2009. Red blood cell membrane fluidity in the aetiology of multiple sclerosis.  J Membr Biol 232:25-34. PMID: 19915887 DOI: 10.1007/s00232-009-9213-1
  9. Van Toorn R, Schoeman J, Solomons R, Rensburg M, Van Rensburg SJ. 2010. Iron status in children with recurrent episodes of tumefactive cerebral demyelination. J Child Neurol 25(11):1401-1407.
  10. Van Rensburg SJ, Van Toorn R. 2010. The controversy of CCSVI and iron in multiple sclerosis: is ferritin the key? Neurology 75(18):1581-1582. PMID: 20395637 DOI: 10.1177/0883073810366179
  11. Hon GM, Hassan MS, van Rensburg SJ, Abel S, Erasmus RT, Matsha T. 2011. Monounsaturated fatty acids in blood cell membranes from patients with multiple sclerosis. Inflammation. 34(6):681-7. PMID: 21120595 DOI: 10.1007/s10753-010-9279-z
  12. Hon GM, Hassan MS, Van Rensburg SJ, Abel S, Erasmus RT & Matsha T (2011) Peripheral blood mononuclear cell membrane fluidity and disease outcome in patients with Multiple Sclerosis. 2012.  Indian Journal of Hematology and Blood Transfusion 28(1):1-6.  PMID: 23449275 PMCID: PMC3311971 DOI: 10.1007/s12288-011-0087-x
  13. Hon GM, Hassan MS, Van Rensburg SJ, Abel  S, Erasmus RT & Matsha  T (2011) Plasma non-esterified fatty acids in patients with Multiple Sclerosis. Neurology Asia 16(3):217–222.
  14. Hon GM, Hassan MS, van Rensburg SJ, Erasmus RT, Matsha TE. 2012. Assessment of Epstein-Barr virus in blood from patients with multiple sclerosis. Metab Brain Dis. 27(3):311-8. PMID: 22407028 DOI: 10.1007/s11011-012-9292-z
  15. Van Rensburg SJ, Kotze MJ, Van Toorn R. 2012. The Conundrum of Iron in Multiple Sclerosis – Time for an Individualised Approach. Metab Brain Dis. 2012;27(3):239-53. PMID: 22422107 PMCID: PMC3402663 DOI: 10.1007/s11011-012-9290-1
  16. Kotze MJ, Van Rensburg SJ. 2012. Pathology supported genetic testing and treatment of cardiovascular disease in middle age for prevention of Alzheimer’s disease. Metab Brain Dis. 2012;27(3):255-66. PMID: 22552896 PMCID: PMC3429783 DOI: 10.1007/s11011-012-9296-8
  17. Davis W, van Rensburg SJ, Cronje FJ, Whati L, Fisher LR, van der Merwe L, Geiger D, Hassan MS, Matsha T, Erasmus RT, Kotze MJ. The fat mass and obesity-associated FTO rs9939609 polymorphism is associated with elevated homocysteine levels in patients with multiple sclerosis screened for vascular risk factors. Metab Brain Dis. 2014 29(2):409-419. PMID: 24532085 DOI: 10.1007/s11011-014-9486-7
  18. Nelson MC, Isaacs F, Hassan MS, Kidd M, Cronje FJ, Van Rensburg SJ. 2014. Prevalence of abnormal bloodflow patterns and effects of biochemistry and lifestyle factors on the major neck vessels in patients with Multiple Sclerosis in the Western Cape, South Africa. Medical Technology SA 28 (1):26-33
  19. van Rensburg SJ, van Toorn R, Moremi KE, Peeters AV, Oguniyi A, Kotze MJ.  Multiple sclerosis-like diagnosis as a complication of previously treated malaria in an iron and vitamin D deficient Nigerian patient. Metab Brain Dis. 2016; 31(1):197-204. PMID: 26746433 DOI: 10.1007/s11011-015-9788-4
  20. Herbert E, Engel-Hills P, Hattingh C, Fouche JP, Kidd M, Lochner C, Kotze MJ, van Rensburg SJ. Fractional anisotropy of white matter, disability and blood iron parameters in multiple sclerosis. Metab Brain Dis. 2018;33(2):545-557. doi: 10.1007/s11011-017-0171-5. PMID: 29396631 DOI: 10.1007/s11011-017-0171-5
  21. van Rensburg SJ, Peeters AV, van Toorn R, Schoeman J, Moremi KE, van Heerden CJ, Kotze MJ. Identification of an iron-responsive subtype in two children diagnosed with relapsing-remitting multiple sclerosis using whole exome sequencing. Mol Genet Metab Rep. 2019;19:100465. doi: 10.1016/j.ymgmr.2019.100465. eCollection 2019 Jun. PMID: 30963028 PMCID: PMC6434495 DOI: 10.1016/j.ymgmr.2019.100465
  22. Burger A, Kotze MJ, Stein DJ, Janse van Rensburg S, Howells M. The relationship between measurement of in vivo brain glutamate and markers or iron metabolism: A proton magnetic resonance spectroscopy study in healthy adults. Eur J Neuroscience 2020; 51(4):984-990. PMID: 31585485 DOI: 10.1111/ejn.14583
  23. van Rensburg SJ, van Toorn R, Erasmus RT, Hattingh C, Johannes C, Moremi KE, Kemp MC, Engel-Hills P, Kotze MJ. Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part I. Targeting a metabolic model rather than autoimmunity. Metab Brain Dis. 2021 Aug;36(6):1151-1167. PMID: 33909200 DOI: 10.1007/s11011-021-00711-w
  24. van Rensburg SJ, Hattingh C, Johannes C, Moremi KE, Peeters AV, van Heerden CJ, Erasmus RT, Zemlin AE, Kemp MC, Jaftha M, Khine AA, Potocnik FCV, Whati L, Engel-Hills P, van Toorn R, Kotze MJ. Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part II. Insights from two MS cases. Metab Brain Dis. 2021 Aug;36(6):1169-1181. doi: 10.1007/s11011-021-00712-9. PMID: 33710528.
  25. Merlisa Kemp, Clint Johannes, Susan J van Rensburg, Martin Kidd, Ferial Isaacs, Maritha J Kotze, Penelope Engel-Hills. Disability in Multiple Sclerosis is Associated with Vascular Factors: An Ultrasound study.  medRxiv 2022.09.11.22279820; doi: https://doi.org/10.1101/2022.09.11.22279820
  26. Kemp MC, Johannes C, van Rensburg SJ, Kidd M, Isaacs F, Kotze MJ, Engel-Hills P. Disability in multiple sclerosis is associated with vascular factors: An ultrasound study. J Med Imaging Radiat Sci. 2023 Jun;54(2):247-256. doi: 10.1016/j.jmir.2022.11.017. PMID: 36528497
  27. Johannes C, Moremi KE, Kemp MC, Whati L, Engel-Hills P, Kidd M, van Toorn R, Jaftha M, van Rensburg SJ, Kotze MJ. Pathology-supported genetic testing presents opportunities for improved disability outcomes in multiple sclerosis. Per Med. 2023 Mar;20(2):107-130. PMID: 37194915 DOI: 10.2217/pme-2022-0016
  28. Mariaan Jaftha, Frances Robertson, Susan J van Rensburg, Martin Kidd, Ronald van Toorn, Merlisa C. Kemp, Clint Johannes, Kelebogile E. Moremi, Lindiwe Whati, Maritha J Kotze, Penelope Engel-Hills. White matter lesion volumes on 3-T MRI in people with MS who had followed a diet- and lifestyle program for more than 10 years. medRxiv 2024.04.06; doi: https://doi.org/10.1101/2024.04.04.24305252