FIRST UP CONSULTANTS

Development of natural

products for the treatment

and management of type 2

diabetes mellitus

Presenter:

Dr. Shadae Foster

The University of the West Indies, Mona

Dr. Lowell Dilworth

Dr. Rudy Lisa Lindo

Texas A&M University, Corpus Christi

Dr. Felix Omoruyi

RESEARCH TEAM

INTRODUCTION

Diabetes is an important public health problem and is one of four priority

noncommunicable diseases (NCDs) targeted for action by world leaders.

Challenges:

There is no cure for diabetes mellitus

Treatment is costly

Have undesirable side effects.

Possible Solution:

Natural alternative anti-hyperglycaemic remedies with minimal or no side

effects.

It is estimated that 425 million people are living with diabetes (IDF, 2018).

By 2045, projections show this number rising to some 629 million diabetics globally.

INTRODUCTION

Readily available

Cost effective

Safe

Unique natural

Minimal to no side effect

RATIONALE

Studies have reported that phytic acid and inositol individually showed insulin secretory and anti-cancer properties (Barker et al.2002, 2009; Berggren & Barker 2008).

However, a greater anti-cancer effect was observed when phytic acid and inositol were administered as a combination (Shamsuddin et al. 1998).

The use of phytic acid and inositol combinations in the treatment of type 2 diabetes has never been previously studied.

Our research group theorized that the combined phytic acid and inositol product may be more effective at managing diabetes than IP6 or inositol alone.

MAIN OBJECTIVE

This project assessed the efficacy of combined phytic acid and

inositol as a novel treatment option for type 2 diabetes

mellitus and its potential for nutraceutical applications.

Research has shown that inositol and

IP6 have virtually no toxicity and is

very safe for consumption, even with

long term administration. (Ullah and

Shamsuddin, 1990).

Phytic and inositol is naturally present (0.4%–6.4%) in all living cells and

wide variety of plant foods (Vucenik & Shamsuddin, 2003), especially:

Wheat bran

Whole grains

Legumes

PHYTIC ACID AND INOSITOL

Phytic acid was generally considered to be an anti-nutrient be

because interferes with the absorption of minerals from the diet.

However, Walker and colleagues (1998), demonstrated that the

“anti-nutrient” effect of phytic acid is only manifested when:

A large amount of phytic acid

A diet low in trace elements

PHYTIC ACID

METHOD

EXPERIMENTAL DESIGN

High-fat diet

Streptozotocin

(35 mg/kg bw)

Type 2 diabetics

Non-diabetics Normal Control (NC)

Standard rat chow

Non-diabetics

Diabetic Control (DC)

Phytic acid + Inositol

(IP6+INO)

High-fat control (HFC)

Glibenclamide (Glib)

(6 rats per group) •Blood glucose

•Body weight

•Food and fluid intake

•Insulin

•lipid composition

•Antioxidant activity

•Metabolic enzymes activity

•ATPase activity

•Histological study

•Hematological analysis

•Blood chemical parameters

RESULTS &

DISCUSSION

55

65

75

85

95

105

115

125

135

0 30 60 90 120 150 180 210

Blo

od

Glu

cose

Co

nce

ntr

atio

n (

mg/

dL)

Time (minute)

Figure 1. Oral glucose tolerance test of inositol, IP6 and

its combination at a dosage of 650 mg/kg body weight

via oral gavage versus a control in normoglycemic

Sprague-Dawley rats

Normal Control IP6 (650 mg/kg BW)

INO (650 mg/kg BW) IP6+INO (650 mg/kg BW)

*

* *

0

100

200

300

400

500

600

700

2 3 4 5 6 7 8

Mean N

on

-fast

ing B

loo

d G

luco

se (

mg/d

L)

Time (week)

Figure 2. Non-fasting Blood Glucose Concentration

in Diabetic Rats Treated with Combined IP6 &

Inositol Supplement or Glibenclamide versus

Controls

NC HFC DC IP6+INO Glib.

55

65

75

85

95

105

115

125

135

0 30 60 90 120 150 180 210

Blo

od

Glu

cose

Co

nce

ntr

atio

n (

mg

/dL)

Time (minute)

Figure 1. Oral glucose tolerance test of inositol, IP6 and its combination

at a dosage of 650 mg/kg body weight via oral gavage versus a control in

normoglycemic Sprague-Dawley rats

Normal Control IP6 (650 mg/kg BW) INO (650 mg/kg BW) IP6+INO (650 mg/kg BW)

*

* *

0

20

40

60

80

100

120

140

160

Total Cholesterol Triglyceride HDLMea

n L

ipid

Conce

ntr

atio

n (

mg/d

L)

Figure 3. Serum Lipid Profile of Diabetic Rats

Treated With IP6 & Inositol Combination versus

Glibenclamide NC HFC DC IP6+INO Glib

a

a a a

ab

ab

bc

ab

a a

a

a

c

a

Table 1. Liver Lipid Profile of Diabetic Rats Treated with

Combined IP6 and Inositol Supplement or Glibenclamide

versus Control

Groups

Triglyceride

(mg/g tissue wet

weight)

HDL

(mg/g tissue wet weight)

NC 13.22 ± 1.4a 0.134 ± 0.019a

HFC 19.80 ± 2.49a 0.114 ± 0.016ab

DC 26.93 ± 3.21b 0.067 ± 0.016b

IP6+INO 16.57± 0.63a 0.134 ± 0.020a

Glib 19.69 ± 1.52a 0.119 ± 0.022ab

Note: The bars and figures with different superscript letters are

significantly different at p < 0.05.

NC

HFC

IP6 &

INO Glib

Figure 4. Photomicrograph of haematoxylin and eosin stained pancreas tissue section of the

normal control (NC), high-fat control (HFC), IP6 and inositol treated diabetic group (IP6 &

INO) and glibenclamide treated diabetic group (Glib). Mag × 200

DC

Figure 5 Photomicrograph of Haematoxylin and Eosin Stained Pancreas Tissue

Section of the Diabetic Control (DC) Mag × 200

Table 6: The diameter of islets and number of islets/pancreas section in diabetic

rats treated with combined IP6 & inositol supplement or glibenclamide

Groups Diameter of islets

(mm)

Number of islets/pancreas

(N/10 mm2)

NC 0.367 ± 0.042a 13.60 ± 1.28a

HFC 0.217 ± 0.060b 14.00 ± 1.67a

DC 0.100 ± 0.00b 5.00 ± 0.07b

IP6+INO 0.183 ± 0.047b 10.33 ± 1.33a

Glib 0.200 ± 0.045b 4.75 ± 0.25b

Summary

Reducing blood glucose level

Reducing insulin resistance

Regulate appetite (Polyphagia)

Regulate thirst (Polydipsia)

Regulate lipid abnormalities

(Dyslipidemia)

Regulate body weight

Reduce oxidative stress

As effective More effective

No Adverse effects on liver integrity

Summary

No Adverse effects on kidney integrity

Pancreatic Restorative/Protective Effects

TRANSLATIONAL RESEARCH

LAB MARKET

Poor

Lifestyle

Practices

Product Development- Multi-functional

Easy and Convenient

Replace unhealthy Food

Help with portion and calorie control

Low glycemic index and lipid level

Balance nutrition

Filling and satisfying

Diabetic meal replacement beverage -

Multi-functional

Regulate appetite

Assist with weight loss

Lower cholesterol levels

Regulate blood glucose level

Increase antioxidant level

Reduce insulin resistance

Improve pancreatic function

Balance nutrition

Nutraceutical Supplement

There is a shift in the consumer

preference from pharmaceutical

drugs containing synthetic

ingredients to nutraceuticals

supplements.

Social and Economic Value

Estimated global cost associated with diabetes in 2015 was $US 1.31 trillion (Bommer et al, 2017).

In 2011, the National Health Fund paid $JM 616,461,903 to beneficiaries for diabetes alone.

The nutraceutical drug market share was valued at over $US 383 billion in 2017 and is projected to reach $US 561.4 billion by 2023 (Staista, 2017).

Social and Economic Value

Diabetes

220,000

(13.6%)

Obesity (26.8%) and

overweight (58.4%)

Target market 10,000

Glucerna

$US 3.45

$US 9.9 million

Phytitol

$US 2.75

$US 8 million

Non-diabetics:

High cholesterol,

Prediabetics etc.

Net profit

$US 3.4

million

Social and Economic Value

How can Jamaica benefit from our nutraceutical innovation?

Improved well-being and quality of life

Reduction in the country’s healthcare bill

Increased foreign-exchange earnings

Increased employment

Improved social and economic well-being of all persons involved

What’s next?

Additional product research and development activities on the

project presented within is being undertaken to see to the

commercialization of our innovation.

Since we are developing finished formulations with the

inclusion of other ingredients besides our active ingredients, we

intend to undertake additional work which includes activities to

confirm the product stability and efficacy.

Other research projects

I’m currently undertaking research that will qualify and quantify the

nutritional, chemical and biological composition of under-utilized

plants in Jamaica that are currently being used by the indigenous

community members for its nutritional and medicinal properties.

This study aims to identify and assess the bioactive substances

present in the plants that will explain and verify their folkloric

medicinal uses and explore their potential for product development.

PUBLICATIONS (Peer reviewed Journal Articles):

Shadae R. Foster, Felix O. Omoruyi, Juan Bustamante, Ruby L. A. Lindo, & Lowell L. Dilworth (2016). The

effect of combined inositol hexakisphosphate and inositol supplement in streptozotocin-induced type 2 diabetic

rats. International Journal of Experimental Pathology, 97(5), 397-407.

Foster, S. R., Dilworth, L. L., Thompson, R. K., Alexander-Lindo, R. L., & Omoruyi, F. O. (2017). Effects of

combined inositol hexakisphosphate and inositol supplement on antioxidant activity and metabolic enzymes in

the liver of streptozotocin-induced type 2 diabetic rats. Chemico-Biological Interactions, 275:108-115.

Henry IC Lowe, Denise K Daley, John Lindo, Chenee Davis, Lois Rainford, Shelly-Ann Hartley, Charah

Watson, Cheryl Chambers, Glendee Reynolds-Campbell, Shadae R Foster, Percival Bahadoosingh, and

Camille Thoms-Rodriguez (2017). The Antibacterial and Antifungal Analysis of Crude Extracts from the

Leaves and Bark of Pimenta species found in Jamaica. Journal of medicinal Plant research, 11(38), 591-595,

DOI: 10.5897/JMPR2017.6435.

Shadae R Foster, Lowell L Dilworth, Felix O Omoruyi, Rory Thompson and Ruby L Alexander-Lindo.

(2017). Pancreatic and renal function in streptozotocin-induced type 2 diabetic rats administered combined

inositol hexakisphosphate and inositol supplement. Biomedicine and Pharmacotherapy, 96:72-77.

PUBLICATIONS (Peer reviewed Journal Articles – Pending)

Shadae R Foster, Cliff Riley, Melaine Randle, Yvonne Bailey Shaw, Charah T

Watson. Phytochemical screening of active secondary metabolites presents in raw and

differentially processed Entada Gigas seed: indigenous and medicinal uses. Journal of

Medicinal Plant Studies. Manuscript in preparation.

Shadae R Foster, Lowell L Dilworth, Jean Sparks, Ruby L Alexander-Lindo and

Felix O Omoruyi. Combined inositol hexakisphosphate and inositol supplement

consumption improves serum alpha-amylase activity and hematological parameters in

streptozotocin-induced type 2 diabetic rats. Journal of pharmacological Sciences. (In

press).

CONFERENCE PRESENTATIONS (Published Abstracts)

S. R. Foster (Author & Presenter), R. L. Alexander Lindo, L. L Dilworth, J. Bustamante, F. O. Omoruyi. (2016). Anti-

diabetic properties of combined inositol hexakisphosphate (IP6) and inositol in streptozotocin-induced type 2 diabetes

mellitus Sprague-Dawley rats. American Association for Clinical Chemistry (AACC) Annual meeting abstracts, B-003.

Pp 28.

S Foster (Author & Presenter), F Omoruyi, L Dilworth, J Bustamante and R Alexander-Lindo. (2016). The effect of

inositol hexakisphosphate (IP6) and inositol combination on renal and hepatic function and antioxidant status in

streptozotocin-induced type 2 diabetes mellitus Sprague-Dawley rats. West Indian Medical Journal, 65 (1):34.

SR Foster (Author & Presenter), LL Dilworth, FO Omoruyi, J Bustamante and R Alexander-Lindo. (2015). Inositol

and Inositol Hexakisphosphate (IP6) Combination lowers fluid and food intake in Type 2 Diabetes Mellitus Sprague-

Dawley rats. West Indian Medical Journal, 64(4):26. Oral presentation delivered at the Faculty of Medical Sciences

Conference. 24th Annual Research Conference and Workshop on Cancer, a Growing Public Health Priority in the

Caribbean. The University of the West Indies, Mona, Kingston, Jamaica.

Foster, S. (Author & Presenter), Alexander-Lindo, R., Omoruyi, R., Bustamante, J. and Dilworth, L. (2015). The Effect

of inositol and inositol hexakisphosphate (IP6) combination on blood glucose concentration and lipid metabolism in

type 2 diabetes mellitus Sprague-Dawley rats. West Indian Medical Journal, 64 (1):37.

AWARDS AND HONORS

Best Poster Presentation Award, University Diabetes Outreach Programme (UDOP)

Conference (2015)

Best Poster Presentation Award, University Diabetes Outreach Programme (UDOP)

Conference (2016)

The University of the West Indies Postgraduate Scholarship (2013 - 2015)

Department of Basic Medical Sciences Postgraduate Award (2012-2013 & 2015-2017)

The University of the West Indies Dean’s list Award 2010-2011

M and M Jamaica Limited Scholarship (2009-2010)

Acknowledgements

My supervisors: Dr. Lisa Lindo & Dr. Lowell Dilworth

Dr. Felix Omouryi & Dr. Juan Bustamante (Texas A&M university)

Dr. Rory Thompson (Pathologist)

Office of Graduate Studies and Research

The University of the West Indies

Texas A & M University (Corpus Christi and Kingsville)

Marshall Arts Solutions - Gawaine Marshall

Scientific Research Council

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Am. J. Physiol. Endocrinol. Metab. 283, E1113– E1122.

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