Papaya and Sick People

When we decide to explore plant based medicine, safety is the number one consideration. Mission critical is do no harm.

Many years ago, while working in Uganda, a friend with connections agreed with this hypothesis. He commissioned a scientific study to determine the LD50 of papaya.

LD50 is the lethal dose which kills 50% of the subjects. This test is performed using laboratory rodents. Not very nice but progress is costly.

Following are the results and recommendations. Please consider this scientific evidence as you consider recommending papaya for your patients. I believe they will thank you. I have benefited big time from this. I eat a 3-4 inch square of fresh leaf daily while in the tropics. My stomach is very strong as a result!! No missed days of work or missed nights sleep for emergency visits. No staying close to the washroom. No smooth muscle relaxants. Just smooth sailing!!

The link below goes to an LD50 study done at the Makerere University in Kampala, Uganda

Pleaf.pdf

Ebola and Plant based Treatment Options

I am constantly amazed at the medical communities objective in light of new outbreaks of diseases which have plagued man kind for millenia – let’s develop a vaccine.

Vaccines have yielded huge benefits to the human race, don’t get me wrong. However, people who live in remote areas and cannot access such treatment, need options. These people would benefit from not being subject to the weak link of supply chains, which ever malady they may have.

When I ponder such diseases as malaria with literally billions of cases annually, pills do not cut it for poor people. One set back in the move toward plant based solutions is pill sellers. Wealth creation has its roots in a healthy population. Pill sellers like their business. And it’s profits. But how much more could they make if the population was well and able to work to capacity? I venture to say they could make more selling windows, doors and construction materials. These are legitimate businesses in which pill sellers could participate.

Papaya leaves as medicineTake a boo at this article on papaya – one of my favorites for staying healthy in the tropics. It treats or prevents two of the 4 big killers – malaria and dysentery. I am walking proof that it works!!

Photo to follow!!!

http://papayaleaves.wordpress.com/page/2/

Kind Regards, Tim

Have a marvelous tropical holiday, topped off with a cup of papaya leaf tea daily!! Do some research to see if this product is suited to you!!

My condolences to those who have lost loved ones to the ebola outbreak.

Papaya Leaf Study from Kampala, Uganda

Several years ago I was able to get this study done at the Makerere University in Kampala, Uganda. Hope you find it good bed time reading!! The tables do not translate into the blog but the other text is fine. Please let me know what you think.
papaya leaves for medical use
Preliminary Report

ACUTE PRECLINICAL SAFETY STUDY of the CARICA PAPAYA LEAVES USED AS MALARIA PREVENTITIVE IN WESTERN UGANDA

INTRODUCTION
The role of plant/herbal medicines in the treatment and prevention of diseases is regaining its place in community health care. In Uganda a number of plants are currently used in the communities to treat and prevent diseases. One such plant medicine is the Carica papaya (pawpaw) leaves boiled and drunk every week to prevent malaria. The effectiveness of such medicines remains unknown due to lack of scientific evidence.

AIM
In this study the safety profile i.e. acute toxicity and sub chronic toxicity of the Carica papaya leaves was investigated using the WHO recommended laboratory animal test models and procedures. The findings in this study are useful guide for the clinical studies that may be conducted.

METHODS
Preparation of the Extract.

The freshly harvested leaves of Carica papaya were weighed, chopped, and extracted in ethanol-acetic acid (90%+10%) solvent mixture by cold soaking for 5 days and filtered (This solvent mixture gives the highest yield of alkaloids and other active principles and also its polarity is closest to that of water a solvent used in the communities). The marc was discarded and the filtrate concentrated in an oven temperature of 50 degrees C to solid state. Known weights of the solid extracts were suspended in distilled water and the filtrates obtained. The filtrate was spanned at 3500 rev/min for five seconds and a clear supernatant obtained. The concentration of the supernatant was obtained by subtracting the total weight of the dry filter (residue) from the original extract weight suspended.

Single Dose / Acute Toxicity profile.

This test in addition to providing the degree of lethality of the medicine/extract also provides useful pharmacological and clinical effects resulting from doses administered by the oral route and one other route in lethal dose range to the test models. The test also aids the estimation of the median lethal dose, which is very useful in classification of the test substance based on its toxicity.

The median lethal dose therefore was determined by first obtaining the approximate median lethal doses for the intra-peritoneal (IP) and oral (PO) routes. Ten pairs of mice were administered doses 500mg/kg, 1500mg/kg, 2000mg/kg and 2500mg/kg by the ip route. Another set of 10 mice in pairs received by the oral route doses 1500mg/kg, 2500mg/kg, 5000mg/kg, 7500mg/kg and 1000mg/kg. The mice had been fasted for 18 hours. The mice were observed for 48 hours and the oral and IP dose that killed 50% of the mice gave the approximate median lethal doses (LD50). The IP route showed approximate LD50 at 1000mg/kg while the oral route gave two points 2500mg/kg and 7500mg/kg. A repeat of the oral dose gave more variations suggesting variable bioavailability due to possible variation in first pass effect following oral administration of the extract. Such various are observed when acetylcholine like alkaloids is administered to rodents by the oral route. A repeat of the IP dosing twice showed consistency in the observed effects.

The actual IP median dose was determined using doses chosen in such a way that five dose levels were used, one dose equivalent to the approximate median lethal dose by the oral route, two doses below and two doses above it. The doses used were 500mg/kg, 700mg/kg, 1000mg/kg, 1200mg/kg and 1500mg/kg. These doses were administered to five groups of six mice each while the sixth group of six mice received equivalent volume of distilled water. The median lethal dose was then determined by both the graphical and arithmetic methods described in fundamentals of experimental pharmacology by Ghosh(1984)

Repeated dose toxicity/ sub chronic Toxicity
This test provides toxicities and side effects that may arise from long-term use of a drug. Effects on major organs such as liver, kidneys, skin, bone marrow etc are studied.

In this study multiple or repeat dose effects were assessed by administering daily oral doses equivalent to 1%, 10% and 25% of the IP LD50 (843mg/kg) to young growing male rats aged 6 weeks for three weeks. Male rats (24) from the faculty of veterinary medicine Makerere University were purchased were acclimatised in the study laboratory for 1 week and were fed on standard diet (mice pencil).
On the study day, the rats were randomly divided into four groups of six each. The average group weight was determined and recorded. C. papaya leaf extract was prepared and administered in doses 8.4mg/kg, 84.3mg/kg and 210mg/kg to groups I, II and III respectively. Group IV the control group received daily equivalent volume of water. The weights of the animals were determined every third day and recorded. Other observations were recorded on the daily basis. At the end of the dosing phase the animals were anesthetized with chloroform and blood equivalent to 4 mls drawn from the venacava. The blood was sent for clinical chemistry and hematology. The animals died soon after all the blood was drawn. The major organs were weighed and together with the whole animal were sent to a veterinary pathologist for autopsy.

RESULTS
Approximate IP Median Lethal Dose Determination in Mice

Dose(mg/kg)
500
1000
1500
2000
2500
No. per group
2
2
2
2
2
No. dead
0
1
2
2
2

Approximate IP Median Lethal Dose in Mice = 1000mg/kg

Approximate Oral Median Lethal Dose Determination in Mice
Dose (mg/kg)
1500
2500
5000
7500
10000
No. per group
2
2
2
2
2
No. dead
0
1
0
1
2

Approximate Oral Median Lethal Dose in Mice was highly variable indicating possible variation in oral bioavailability of the active components.

Actual IP Median Lethal Dose Determination.
Group
Dose(mg/kg)
InDose
Dead/Total
Dead%
Corrected%
Probit
I
500
2.7
1 of 6
16.7
16.7
4.05
II
700
2.8
2 of 6
33.3
33.3
4.56
III
1000
3
3 of 6
50
50
5
IV
1300
3.11
5 of 6
83.3
83.3
5.95
V
1500
3.18
6 of 6
100
95.8
6.75
VI
0.00(control)

0 of 6
0

Corrected formula: For the 0% dead: 100(0.25/n)

For the 100% dead: 100((n-0.25)/n) Where n is the number of animals in the group.

LD50 DETERMINATION BY GRAPHICAL METHOD

P
r
o 8
b 6
i 4
t 2
s 0 ____________________________________________________________________
2.6 2.7 2.8 2.9 3 3.1 3.2 3.3
Log (dose)

Actual oral Median Lethal Dose by Graphical Method.

From the graph probit 5.0 corresponds to log Dose equal to 2.92

Antilog (2.92) = Median Lethal Dose = 831.76 mg/kg.

Standard error of LD50 = (LogLD84-LogLD16)/ √2N
(3.09-2.68)/ √12 = 0.41/3.46 = 0.12

Actual Median lethal dose by the arithmetic method described by Karber.

Group
Dose (mg/kg)
No. of Mice
Dose diff- erence (a)
Dead
Mean Mort- ality (b)
Product (axb)
1
500
6

1


2
700
6
200
2
1.5
300
3
1000
6
300
3
2.5
750
4
1300
6
300
5
4
1200
5
1500
6
200
6
5.5
1100

3350

LD50 = 1500-(3350/6) = 1500 – 558.33 = 941.67mg/kg.

The two methods show that the median lethal dose, which is a measure of acute toxicity / single dose toxicity, lies between 800mg/kg to 1000mg/kg for the IP route.

The approximate oral bioavailability of the extract in mice is 2.5. The estimated oral median lethal is above 2500mg/kg.

Summary of Observations in mice following Acute Dose.
Inactivity/behaviour of the mice
Oral doses
Intraperitonial doses
1. Photophobia

2. Feeding

3. Aggressiveness

4. Respiration

5. Piloerection

6. Lacrimatiom

7. Diarrhoea

8. Urination

9. Convulsions
1. -Dose dependent

2. -↓sed & dose dependent

3. – none

4.-↑sed & dose dependent

5. None

6.- Marked and not dose dependent
7.- None

8. -Marked & not dose dependent
9. -Mild & not dose dependent
1. – Dose dependent

2.-same as oral

3.-same as oral

4.- same as oral

5.- same as oral

6. None

7. Same as oral

8. None

9. Same as oral

-At Doses greater 5000mg/kg by oral route, the effects occurred within 15-30 minutes while at lower doses the effects delayed by up to 5 hours.
-The effects were prolonged; some up to 10 hours indicating the drug probably has a long half-life/duration in the body.

-For intraperitoneal (IP) route, doses greater 500 mg/kg gave immediate effect.

-IP doses greater than 1000mg/kg were lethal within 30 to 60 minutes of administration.

-A unique difference noted was the diuretic (water and salt loss via urine) and diaphoretic (water and salt loss via sweat) effects by the oral route, which did not occur following the IP route doses. This could imply that the extract active ingredients under biotranformation when given by the oral route into active metabolite(s) with diuretic activities.

Growth Suppression Effects in Rat Models
Time(days)
I
II
III
IV

93.0±10.9
96.0±9.0
86.6±11.9
93.5±9.9

108.6±9.5
109.6±9.3
94.1±8.7
113.03±12.3

106.6±8.4
109.3±14.4
97.0±8.7
105.8±9.5

125.0±8.6
121.3v15.8
107.0±12.5
126.7±9.7

131.9±8.6
132.0±13.7
101.5±9.6
141.8±9.8

130.5±8.6
143.0±15.3
107.0±7.1
152.0±10.5

146.0±8.5
148.1±15.6
110.4±6.6
157.3±11.7

155.9±7.3
157.6±17.8
115.4±7.9
167.7±12.5

Series=1=gpI, 2=gp II, 3=gp III, 4=gp IV

(A chart of the above results which is presented by the report writers, is not in this presentation.)

The drug suppresses growth significantly at IP doses greater than 200mg/kg administered on daily basis.

Haematology and Clinical chemistry Results for Selected Parameters in The Rat Models

I
II
III
IIII
Haemoglobin
(g/dl)
13.47±0.05
13.53±0.83
13.4±0.87
13.13±3.53
WBC (cells/mm cubed)
4600±400
4466±416
4600±600
4733±305
N (%)
59.0±1.4
66.0±4.0
63.33±4.16
64.67±5.03
L (%)
41.0±1.4
34.0±4.0
36.67±4.16
35.33±5.03
LFT – GOT
– GPT
7.33±1.55
5.0±1.0
9.0±1.0
7.67±0.58
7.67±1.53
6.0±1.0
7.67±1.53
5.67±2.08
RFT – creatine(mg/dl)
0.73±0.15
0.57±0.21
0.47±0.31
0.47±0.23

The drug had little effect on the major drug handling organs even at doses that suppress growth. All the parameters measured were within the normal/physiological ranges.

Observed Rat behaviour following repeated drug dosing compared to the control group.

– Overall the animals did not show significant behavioural changes.
Three animals died. 1 rat in group II and 2 rats in group III developed diarrhoea and lower abdominal tenderness and died. These deaths were not associated with the drug.
None of the animals developed injection necrosis.
All animals in group II and III lost weight; group III had marked weight loss.

Autopsy Results: pending from the pathologist.

Recommendations.

1. The C. Papaya leaf oral median lethal dose is greater than 2000mg/kg. According to the World Health Organisation and the European Union, a herbal drug with median dose above 2000mg/kg is very safe for human use.
2. C. Papaya leaf extract taken daily in oral doses less than 200 x 2.5mg/kg or 0.5g/kg may not be toxic in human beings. i.e. up to 350g = or 8 average leaves decoction consumed daily by an adult should be safe.
3. C. Papaya taken in high doses daily may cause hypotension and electrolyte imbalance in the users.
4. C. papaya taken once a week as herbal tea against malaria should be safe but this claim should be verified by clinical investigations.

Ogwang P. Engeu 1, Tumusiime Ralph 1, Agwaya Moses 1 & Galiwago Budra 2.

1. Natural Chemotherapeutic Research Laboratory – Ministry of Health Kampala, PO Box 4864 Kampala.
2. Faculty of Veterinary medicine, Makerere University, PO Box 7062, Kampala.

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