DIETARY INTERVENTION RESEARCH GROUP (DIRG)

DIETARY INTERVENTION RESEARCH GROUP
affiliated to
COLLEGE OF MEDICINE, UNIVERSITY OF NIGERIA
UNIVERSITY OF NIGERIA TEACHING HOSPITAL
CHIOLIVE INTERNATIONAL MEDICAL RESEARCH ORGANISATION
VISION: to reverse the worldwide rising burden of chronic disease and cancers, and reduce the impact of infectious diseases
MISSION: to address the diet – genome interaction in the aetiopathogenesis of immune dysfunction and chronic diseases by advising, promoting and counselling on Personalized Categorical Food Avoidance (PCFA) nutrition
MOTTO: Prevention is better than cure: dietary intervention addresses the cause.
“Let food be thy medicine and medicine be thy food.” Hippocrates (c. 400 B.C.)
EXHORTATION:
Let us make the world a better place and restore the dignity of Man … so help us God
The Dietary Intervention Research Group (DIRG) has been established in the College of Medicine over the past two years. The inspiration and motivation for setting up DIRG arose from personal observation and insight into the dietary factors which modulate the phenotypic expression of chronic disease by attenuating pro-inflammatory and pro-proliferative immune dysfunction, with apparent side-benefits on anti-infective immunocompetence and antineoplastic immunosurveillance.3,4 The time course of these observations is consistent with modulating effects on gene expression to promote immuno-optimization which attenuates chronic disease expression.
Indeed, the increasing pandemic of non-communicable/ chronic diseases mandates urgent research into possible aetiopathogenic influences. Epidemiological studies show that chronic diseases are often associated: hence, for example, the ‘metabolic syndrome’.1,2 This epidemiological association suggests that chronic diseases may to some extent share common genetic and/ or environmetal predisposing factors.
Pilot observational studies suggest a major role of certain dietary constituents in the phenotypic expression of genetically predisposed chronic disease such as psoriasis and other associated metabolic syndrome disorders (hypertension, type-2 diabetes, abdominal obesity). The suspect dietary constituents include hydrogenated fats and some flavour or sweetener compounds. These compounds consistently engender relapse of a prototypical chronic disease (psoriasis).3,4 The slow, non-dose related, onset of this relapse (1-3 days), and the slower remission (1-3 weeks) upon strict avoidance of culprit ingredients, are consistent with an epigenetic mechanism i.e. receptor-mediated activation of gene expression to induce and aggravate chronic disease phenotype. Early pilot observations have shown antihypertensive and antidiabetic therapeutic effects of the antipsoriatic, personalized categorical food avoidance diet.3-5
Apart from correcting the (more or less organ-specific) pro-inflammatory and pro-proliferative immune dysregulation which mediates chronic/ non-communicable disease, personal experience also indicates benefit on the immune system itself (e.g. less frequent and less severe malaria, time-lapse photographs showing spontaneous healing of chronic onychomycosis). This suggests optimization of the immune response to communicable diseases. This is germane to the increasing threat from antimicrobial-resistant infectious diseases, including the viral haemorrhagic fevers, such as Lassa and Ebola fevers. The approximately 40% who survive Ebola infection are doubtless those with better immunocompetence, which would include diet-mediated immuno-optimization.
Personal observation (family history of prostatic neoplasia, yet very low prostatic specific antigenemia4) also suggests improved immunosurveillance versus neoplastic mutant cells. This would support a role of the personalized dietary intervention in cancer prevention.
Albeit without research grant funding (apart from a donation of 40 home blood pressure monitors from ForaCare AG Suisse), the DIRG has begun a randomized controlled trial to compare conventional dietary advice (consistent with the Dietary Approach to Stop Hypertension, DASH6) with a personalized (interventional) dietary approach which excludes the suspected culprit dietary ingredients. A training course for Personalized Categorical Food Avoidance (PCFA) dietary counsellors is being conducted by the Principal Investigator. The main expected benefits for trial participants are improved control of chronic disease, and reduced need for suppressive drug treatments, with the attendant cost savings and reduced toll of adverse effects. Dietary intervention would not necessarily remove the need for pharmacotherapy, but would at least improve the efficacy, and reduce the burden, of drug treatment. This proposed trial would help confirm an inductive model of the diet – genome interaction in the aetiopathogenesis of chronic disease, derived from decade-long dietary observations in psoriasis.3-5 The clinical trial proposal has been approved by the UNTH ethics committee and registered on www.clinicaltrials.gov. The trial has a PROBE (prospective, randomized, open-label, blinded end-point) design with optional cross-over to the alternative dietary approach after one year.
OBJECTIVE
To compare conventional dietary advice with a personalized dietary approach, as regards their effect on blood pressure and drug requirements in essential hypertension.
SPECIFIC AIMS
1. To ascertain dietary effects on blood pressure in the control diet and interventional diet groups
2. To compare dietary effects on antihypertensive drug treatment requirement and cost in subjects and controls
3. To compare dietary effects on metabolic syndrome – associated co-morbidity of hypertension and its drug treatment requirements
4. To compare dietary effects on organ function tests and metabolic syndrome – associated/ inflammatory biomarkers in subjects and controls
5. To compare dietary effects on RNA, proteomic and metabolomic indices of gene expression in subjects and controls
6. To compare dietary effects on hard clinical (morbidity and mortality) endpoints during the clinical trial and post-study follow-up periods (five years overall)
This pioneering ‘phase 6’ Food and Drug Safety clinical trial, although focused as a ‘proof-of-concept’ study in essential hypertension, potentially has far-reaching implications cutting across the worldwide increasing swathe of chronic diseases, infectious diseases and cancers. We need to realize that for all the effort and expense invested in genome-wide association studies,18 the data collected are unlikely to translate into health benefits for humanity in the foreseeable future because there is too little information on the environmental determinants of adverse gene expression in chronic diseases. Chronic diseases (and impaired immunocompetence versus infectious diseases and cancers) are polygenic: hence there is little hope for benefit from genetic engineering. In any case these genes may confer a survival advantage in times of famine and deprivation (‘thrifty gene’ hypothesis); hence any proposal for tinkering with our genetic make-up may pose ethical difficulties. Modern research in this domain is too focused on genotyping, even to the extent of prophylactic mastectomies or prostatectomy if genetically predisposed to these cancers! Our proposed approach to elucidating the gene-environment interaction in the aetiopathogenesis of immune dysregulation and chronic disease/cancer, is likely to yield far more tangible preventative health benefits for humanity in the foreseeable future i.e. without the need for radical prophylactic surgery, for example.
As part of efforts to develop our research base in Therapeutics, the Principal Investigator has developed a clinical trial centre in Trans-Ekulu, which is being incorporated as the Chiolive International Research Organisation. The PCFADASH-PHT and PCFADASH-HT clinical trials (dietary intervention to reverse hypertension) are being conducted by the DIRG partly at CIMRO, as well as at the College of Medicine and the UNTH. A Clinical Research Coordinator has been employed by the PI to help run these clinical trials.
OTHER DIRG PROJECTS
Some of these projects are already underway. Others have proposals which are being or have been developed. These clinical trials are proposed on the basis of anecdotal observations in patients of marked improvement from the dietary intervention i.e. open, uncontrolled studies without sophisticated studies of gene expression etc.
Rat studies in nutritoxigenetics17
Mr Nnadozie (PhD student), Dr Eze (MSc student), Prof Chijioke
PCFADASH-PET (dietary intervention to prevent/ control pre-eclampsia)
Dr L. Onah (MSc student) et al
PCFADASH-PSO (dietary intervention to abate/control expression of psoriasis)
Dr U. Ojinmah et al
PCFADASH-T2DM (dietary intervention to control type-2 diabetes)
Dr E. Young et al
PCFADASH-ASTHMA (dietary intervention to abate asthma)
Dr N. Nwosu et al
DIRG MEMBERS, AUDITOR, PROSPECTIVE COLLABORATORS
Members of the DIRG are organised into the following teams:
a) Aggregate cardiovascular risk
Dr Anisiuba, Prof Chijioke, Dr Delles, Prof Onwasigwe
b) PCFA dietary counsellors
MLS Nubila, Dtn Okwara, Dr Ekwe, Dr Oji, Dr Nwonu, Dr Okolo, Sec Ibenegbu,
Mr Nnadozie, SNO Chiegboka, Dr Muobike, Dr Aneziokoro, Dr Chijioke,
Mrs Okoli, Prof Chijioke
Dietary Counselling Logistics Officers (DCLOs) / informed consent process
MLS Nubila, Mrs Okoli, Dtn Okwara, Mr Nnadozie, Dtn P.Eze
c)     Endpoint Assessment Logistics Officers (EALOs) / initial informed consent
Dr Nwosu, Dr A.Eze, Dr Abonyi, ?Dr Akandu, SRN Ukwa, Dr Uzoke, Dr Mbadiwe, Dr Ajah (MSc student)
Laboratory assessment logistics officers (EALOs)
MLS Onah, MLS Eleazar, Dr Anusiem, MLS Okpe, MLS Nwadike, Dr Udoh
d) Health economics assessment/ clinical trial budget
Prof Onwujekwe, Mr Okoli
e) Laboratory tests/ gene expression studies (‘-omics’)
Dr Maduka, Dr Delles, Dr Anusiem, MLS Onah, Dr Nna, MLS Eleazar,
Prof Okpala
f) Conventional dietary advice and counselling
Nutritionist P.Eze at CIMRO; Dietary counsellors at MOP, UNTH; Dtn Onwuka-Kalu
g) Pharmacotherapeutic/pharmaco-economic assessment
Pharm Okoye, Pharm Gbenimachor, Pharm Ironkwe, Prof Onwujekwe
h) Physiotherapy assessment
Mrs Chigbo
i) Dietetic/nutri-economic/ anthropometric assessments
Dr Mrs Ndiokwelu, Prof Onwujekwe, Mr Okoli (CIMRO anthropometry by RN Ukwa, Dr Eze)
j) Recruitment/ Clinical assessment
Dr Nwosu, Dr Abonyi, Dr Eze, RN Ukwa, Dr Mbadiwe
k) Cardiovascular assessment
Prof Anisiuba
l) Database, data entry, data analysis
Prof Chijioke, SRN Ukwa, Prof Onwasigwe, Dr Mrs Eleazar
m) Sociology/ socio-economic assessment
Dr Onah, Prof Onwujekwe
PROSPECTIVE COLLABORATORS
Dr C. Delles, Reader and Honorary Consultant Physician, BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, UK
Djims Milius, Global IP, Technology Law & Ethics Consultant, Intuit Economy Solutions, Montreal, Canada
AUDITOR
Dr J-M Maduabuchi, Zeta-12 Inc. (contract research organization, affiliated to the Nigerian Society for Quality Assurance)
There is projected expansion of the Food and Drug Analysis Centre, hitherto based in the departments of Pharmacology & Therapeutics and Pharmacy (UNTH). The department of Food Science and Technology (UNN) is interested in collaborating. The FDA Centre would work in close collaboration with the DIRG, in particular as regards elucidation of the molecular mechanisms of the diet – genome interaction.
UNICOM/ UNN/ UNTH Food & Drug Analysis Centre:
Pharm Okoye, Dr Ndiokwelu, MLS Nubila, Mr Nnadozie, Mr Nwadike, Dr Nwobodo,
Prof Okonkwo, Dr P. Uvere (Dept Food Science Technology)
REFERENCES
1. Qureshi AA, Choi HK, Setty AR, Curhan GC. Psoriasis and the Risk of Diabetes and Hypertension: A Prospective Study of US Female Nurses. Arch Dermatol. 2009;145(4):379-382.
2. Love TJ, Qureshi AA, Karlson EW, Gelfand JM, Choi HK. Prevalence of the metabolic syndrome in psoriasis: results from the National Health and Nutrition Examination Survey, 2003-2006. Arch Dermatol. 2011;147(4):419-424.
3. http:cpcpsoriasis.blogspot.com
4. Chijioke CP, Chijioke OU, Okolo T. Personalized diet for psoriasis: side benefit on blood pressure and metabolic parameters. Presented at 24th meeting of the International Society of Hypertension, Sydney, Australia (30 Sep – 4 Oct 2012).
J Hypertension 2012; 30: e-suppl 1, poster 158
5. Parikh A, Lipsitz SR, Natarajan S. Association between a DASH-like diet and mortality in adults with hypertension: findings from a population-based follow-up study. Am J Hypertens 2009; 22 (4): 409-16.
6. Campbell MJ, Machin D. Medical statistics: a commonsense approach (3rd edition). Chichester, UK: John Wiley, 1999.
7. Noordzij M, Tripepi G, Dekker FW, Zoccali C, Tanck MW, Jager KJ. Sample size calculations: basic principles and common pitfalls. Nephrology Dialysis Transplantation 2010; 25 (5): 1388-1393.
8. Osuji CU, Nwaneli CU, Onwubere BJ, Onwubuya EI, Ahaneku GI. Renal function in patients with hypertension associated congestive cardiac failure seen in a tertiary hospital. International Journal of Nephrology 2012; (2012), Article ID 769103, 5 pages, doi: 10.1155/2012/769103.
9. Burke BS. The dietary history as a tool in research.  Journal of the American Dietetic Association 1947; 23: 1041-1046.
10. Gibson RS. Principles of Nutritional Assessment. New York: Oxford University Press, 1990; pp 165-167.
11. Chijioke CP, Nnadozie JO, Chijioke UO, Okafor OC, Onwasigwe C. The effect of chronic dosing with monosodium glutamate on morbidity, mortality and reproduction in albino wistar rats. Presented at conference of West African Society for Pharmacology, Lagos, 21-23 October, 2013
12. Chijioke CP. Twelve year online case diary of psoriasis: dietary challenge and avoidance effects (in preparation).
13. Chijioke CP, Nnadozie JO, Chijioke UO, Okafor OC, Olusino DB, Oli AN. Chronic toxicity of low dose monosodium glutamate in albino Wistar rats (in preparation).
14. Chijioke CP, Chijioke UO, Okolo T, Ekwe E, Onwasigwe C. Case study of essential hypertension: efficacy of an antipsoriatic dietary approach. Presented at joint meeting of the European Society of Hypertension and the International Society of Hypertension, Athens, Greece (13-16 June 2014). J Hypertension 2014; 32: e-suppl 1, e660
15. Chijioke CP, Chijioke UO, Okolo T, Ekwe E.
Nutritoxigenetics of psoriasis: a ten year online case diary of dietary challenge and avoidance effects on chronic disease phenotype. Presented at World Congress of Basic and Clinical Pharmacology, Cape Town (13-17 July 2014). Basic and Clinical Pharmacology & Toxicology 2014; 115 (Suppl 1): 361
16. Chijioke C, Chijioke O, Okolo T, Ekwe E, Nubila I, Onwasigwe C.
Nutritoxigenetics of hypertension: efficacy of a personalized categorical food avoidance dietary approach. Presented at World Congress of Basic and Clinical Pharmacology, Cape Town (13-17 July 2014). Basic and Clinical Pharmacology & Toxicology 2014; 115 (Suppl 1): 361
17. Chijioke C, Nnadozie J, Chijioke O, Okafor O, Olusina D.
Chronic toxicity of low dose monosodium glutamate and aspartame in albino Wistar rats. Presented at World Congress of Basic and Clinical Pharmacology, Cape Town (13-17 July 2014). Basic and Clinical Pharmacology & Toxicology 2014; 115 (Suppl 1): 353
18. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447(7145): 661-78