CETYLMYRISTOLEATE RESEARCH
also know as cis-9-cetylmyristoleate, CMO
and cetyl myristoleate
The Effect of cis-9-Cetyl Myristoleate
CMO and adjunctive therapy on the course of arthritic episodes
in patients with various auto-immune diseases characterized
by the common terminology "arthritis" and "psoriasis".
A randomised clinical trial
by Dr. H. Siemandi, MD, et al.
Townserd Letter for Doctor's and Patients
August-September, 1997; #169, pp. 58-63
The following are selected
extracts.
CONCLUSION: Cis-9-cetyl myristoleate
treatment and cis-9-cetyl myristoleate plus GH, SC & HC
(referring to nutritional supplements glucosamine hydrochloride
(GH), sea cucumber (SC) and hydrolyzed cartilage (HC)) were
demonstrated to offer significant benefits over the placebo
in the prevention of arthritic episodes. It was further determined
that these results could not be obtained with other standard
arthritic therapies based upon exhaustive reviews of patient
records prior to opening of the study. Cis-9-cetyl myristoleate
and cis-9-cetyl myristoleate plus GH, SC & HC treatment
also seems to permit some relief to autoimmune inflammatory
diseases which may prove to be long-term. This finding could
provide additional evidence for the theory, reflected by the
earlier anecdotal evidence as well as some animal studies,
that cis-9-cetyl myristoleate and cis-9-cetyl myristoleate
plus GS, SC & HC may prove to be of major benefit in the
future treatment of autoimmune diseases.
Study Objective: Recent published
reports offer anecdotal evidence (publication speak for "actual
experience of users") that cis-9-cetyl myristoleate may
provide significant amelioration of various arthritic conditions.
We set out to perform controlled studies to determine if this
material was efficacious, either in the short term, or in
some measurable manner, over a much longer period.
Methods: A prospective, randomised
study design was used to allocate patients to receive cis-9-cetyl
myristoleate, cis-9-cetyl myristoleate plus glucosamine hydrochloride
(GH), sea cucumber (SC) and hydrolyzed cartilage (HC) and
a placebo.
Study design: The study was
a 32 week (8 week cycle, 4 in-hospital & 4 in follow-up),
multicenter, double-blind, randomised, placebo-controlled
parallel trial that compared the efficacy of cis-9-cetyl myristoleate
alone, and cis-9-cetyl myristoleate plus GS, SC & HC,
administered over a period of 30 days, with placebo, for the
treatment of various forms of autoimmune diseases commonly
characterised as arthritis and psoriasis. Out of a dose of
90 grams of total fatty acid esters, 18 grams constituted
cis-9-cetyl myristoleate. Those study patients who received
the support nutrients GS, SC, & HC were given a total
dosage of 18 grams each of these nutrients.
The study was conducted under
the auspices of the Joint European Hospital Studies Program.
This study was designed by a committee, which consisted of
rheumatologists and biostatisticians experienced in the development
and execution of clinical trials. Oversight of the study was
accomplished by an executive committee, composed of the primary
researcher and primary statistician, selected participating
investigators, consultants; and an independent sight committee
consisting of two experienced federally controlled, state
health department rheumatologists and one state health department
biostatistician.
Results Summary: At the start
of this study, the duration, severity, and pattern of arthritic
episodes were found to be similar in the 3 treatment groups.
At the end of the study it was found that the number of arthritic
episodes was significantly reduced, and the duration of episode-free
time was significantly prolonged, in the two cis-9-cetyl myristoleate
groups compared with the placebo group.
At the end of eight weeks,
the response rates were 63.3% with the cis-9-cetyl myristoleate
group and 87.3% in the cis-9-cetyl myristoleate plus GS, SC
& HC group and only 14.5% in the placebo group.
Joint swelling scores improved
in 47.2% in patients using cis-9-cetyl myristoleate alone
and 77.2% in patients using cis-9-cetyl myristoleate plus
GS, SC & HC. Patients experiencing worsening or no reaction
totalled 1.0% in all groups, compared with improvement of
21.1% in placebo group.
DETAILS
Patient population: Four hundred
thirty-one patients entered the study. Of these, 106 were
randomised to receive cis-9-cetyl myristoleate, 84 were randomised
to receive cis-9-cetyl myristoleate plus GS, SC & HC;
226 received a placebo. Fifteen psoriatics received cis-9-cetyl
myristoleate plus GS, SC & HC, plus CM-25% concentration
topical at a 3X quantity ratio. Even though the study was
sponsored by the owners of the respective private hospitals,
recruitment was not limited to the typical fee-paying patients.
Approximately 27% of the patients were actively recruited
in the respective local area. Despite a prolonged accrual
period and careful screening, the loss of approximately 11%
of the starting participants occurred largely because of the
inability to stop the use of tobacco and/or caffeinated beverages
OUTCOME - how "response"
was graded
Clinical assessment: Outcome
measures of disease activity and therapeutic efficacy were obtained
at the time of screening (not more than four weeks before study
entry), randomization at week zero, and thereafter at weeks
1, 2, 3, and 4. Outcome measures included a variety of patient-reported,
clinical, laboratory and radiographic assessments. Patient self-assessment
measures included morning stiffness, night pain, patient overall
assessment and Mobility Functional Index as determined by this
published procedure. Clinical assessment measures included joint
counts, dactylitis, Enthesopathy Index, Spondylitis Articular
Index, chest expansion, modified Schober's test, and finger-to-floor
test as detailed elsewhere in this paper. Additionally, the
presence of symptomatic keratoderma, phalangeal and digital
deformation as measured from a normal range of vertical protrusion
at rest were measured. These tests, singularly and collectively
were then compiled into a patient-by-patient qualitative scale
as; none = 0, mild = 1, moderate = 2, severe = 3 and very severe
= 4.
Laboratory assessment: Laboratory
evaluation included a urinalysis and complete blood cell count,
with leukocyte differential and reticulocyte count. Chemical
surveys and a Westergren erythrocyte sedimentation rate (ESR)
determination were done at every visit by secondary researchers
daily in the two hospital settings. The C-reactive protein
(CRP) level was evaluated at the first and last day of the
hospital stay. At the screening times, blood was drawn for
HLA-B27 typing and RF and ANA determinations.
Radiology assessment: At the
screening visit, all patients had the following radiographs
performed: anteroposterior views of the pelvis and oblique
views of the sacroiliac joints. Adverse drug reactions (ADR's).
Patients were screened for ADR's at every secondary researcher's
visit. Patients were withdrawn from the study medication if
any of the following were found; WBC less than 3000/mm3, absolute
polymorphonuclear count less than 100000/mm3, acute or progressive
decrease in hemoglobin or hematocrit, proteinuria less than
500 mg. for 24 hours, drug fever or significant rash. Biostatistical
considerations. Each patient was classified as a treatment
responder or nonresponder based on the following definition.
Assessment measures were selected a priori, and criteria for
clinical improvement and worsening were defined for each patient
self-assessment and physician assessment (improvement category);
joint pain/tenderness score and joint swelling score (improvement
= decrease by 30%; worsening = increase by 30%). Treatment
response was then defined as improvement in at least 2 of
these 4 measures, one of which must be joint pain/tenderness
or swelling, and ITO worsening any of the 4 measures. The
study was designated with a 90% power for detecting a placebo
response rate of 30% compared with a cis-9-cetyl myristoleate
and cis-9-cetyl myristoleate plus GS, SC & HC response
rate of 50%, assuming a 10% withdrawal rate. This resulted
in a target sample size of 431 patients with an actual sample
size of 382.
In short, the analytical method
was the change in primary and secondary outcome measures from
baselines to the last available follow-ups analyzed using
t-tests for continuous data and chi-square tests for ordinal
and categorical data. Mixed-model analyses were done to characterize
the response patterns over time using SAS PROC MIXED for continuous
data and a program named MIXOR for categorical and ordinal
data. All other analyses were conducted using SAS version
6.08. All statistical tests were two-sided and P0.05 was the
criterion for statistical significance.
AUTHOR'S DISCUSSION POINTS
The results of this trial suggest
that cetyl myristoleate and cetyl myristoleate supporting
formulas may be beneficial in the treatment of many forms
of arthritic based diseases, including: psoriatic arthritis.
The definition of response was determined a priori
and included assessment of joint pain / tenderness and swelling
as well as patient and physician overall assessments. Cetyl
myristoleate and supporting formulas produced the best treatment
response by a factor of 72.8% more patients than did placebo.
Considering the components of response individually cetyl
myristoleate and supporting formulas resulted in 70.3% more
patients having improved as assessed by physician, and 56.1%
more having improved joint swelling. Therefore, while the
amount of treatment response using cetyl myristoleate and
cetyl myristoleate and supporting formulas seems to be consistent
with the treatment affects on joint counts, it is obvious
that there is a statistically significant improvement in the
use of the CM with supporting formulas. The time-line based
response rate of cetyl myristoleate and cetyl myristoleate
supporting formulas, not adequately reflected in data, by
patient, showed the majority of patients responding to cetyl
myristoleate and cetyl myristoleate supporting formulas did
so within the first three weeks. Also, not reflected in the
data, was the continued use of cetyl myristoleate and cetyl
myristoleate supporting formulas beyond the study time limits
and dispensed on request to 21 patients. These 21 patients
were determined to have received only marginal benefits from
cetyl myristoleate and cetyl myristoleate supporting formulas
but one more course of treatment showed responses approximately
equal to the first patient response results.
Cetyl myristoleate and cetyl
myristoleate supporting formulas were well tolerated in this
trial. This finding was not unexpected as cetyl myristoleate
and the cetylmyristoleate supporting formula components are
naturally occurring and have been used as diet supplementation
for many years and are widely available singly and in various
combinations. In summary, cetyl myristoleate and cetyl myristoleate
supporting formulas appear to be beneficial in the treatment
of a wide range of arthritic conditions including long standing
and refractive cases.
Correspondence: Humberto Siemandi,
MD, Ph.D. Primary research administrator at Hospital SM, Avenido
Mazatlan, Rosarito Beach, Baja, California and Institut SM,
Kamin Pamorski, Poland.
STUDY 2
A Study on Dose Effectiveness
and Patient Response Conducted by the San Diego Clinic
The Purpose: The effectiveness
and nontoxicity of CMO (cerasomal-cis-9-cetylmyristoleate)
for arthritis symptoms of pain, inflammation, and impaired
mobility having been previously established, the purpose of
the present study was:
-
To determine optimum dosage levels for various
types of arthritis,
-
To determine if different dosage levels
would be required relative to the severity of each type
of arthritis,
-
To observe response time required for initial
and partial relief of symptoms,
-
To observe response time required for complete
relief of symptoms, and
-
To determine factors influencing subjects
who may not respond to the protocol.
The Subjects: Subjects were
volunteers treated as outpatients. They presented with osteo-arthritis,
rheumatoid arthritis, and other forms of reactive arthritis.
The Study: The study involved
48 subjects. Female subjects (28) ranged from 33 to 82 years
of age. Male subjects (20) ranged from 29 to 74 years of age.
All races and many ethnic backgrounds were represented. Age,
gender, race, and ethnological background appeared to be irrelevant
to patient response in this study.
The Protocol: CMO was administered
orally in the form of 75mg capsules each morning and evening.
The number of capsules and duration of treatment varied for
each group of subjects. Subjects were advised to take capsules
on an empty stomach with water only; and to avoid tea, chocolate,
alcohol, coffee, cola, and other caffeinated drinks for five
hours after taking the capsules. Subjects were advised to
completely avoid chocolate and alcohol during the entire trial
period of two to four weeks duration. With a few exceptions
for subjects who could not function without them, steroids
were also prohibited. Otherwise diet was not controlled in
any way. Subjects were permitted to continue taking their
customary pain and non- steroidal anti-inflammatory medications
until they were no longer needed. Subjects were asked to visit
or call in to report progress at least twice weekly.
The Results: Only two subjects
failed to show marked or complete relief of all symptoms of
pain and limited mobility normally associated with arthritis.
Both of these non-responding subjects had suffered prior hepatic
problems: one from alcohol abuse resulting in cirrhosis of
the liver; the other, a former professional athlete, presented
with considerable liver damage from steroid abuse. Further
studies are necessary to determine the role of liver function
capacity with respect to this protocol. Liver damage resulting
from steroids previously prescribed for arthritis may also
prove to be a factor affecting patient response.
Two other subjects showed less
than a 75% return of articular mobility. The balance of all
subjects reported 80% to 100% return of articular mobility
as well as a 70% to 100% decrease of pain. Relief of inflammation
frequently resulted in at least partial correction of some
deformities. Informal independent trials at clinics, by individual
medical doctors, and other health practitioners appear to
have brought approximately the same results.
GROUP # 1: Mild to moderately
severe osteo-arthritis & reactive psoriatic arthritis
In Group #1, eleven subjects
presenting with mild to moderately severe osteo-arthritis
and one with reactive psoriatic arthritis were supplied with
16 capsules, two 75mg capsules to be taken each morning and
evening for four days. Nine reported about 20% to 30% improvement
in articulation and inflammation and about 40% to 50% relief
of arthritic pain within 36 hours. In these nine subjects
improvement continued rapidly for the next 60 hours, reaching
a 70% to 80% overall improvement by the end of the four days.
Two of the three latter subjects continued to improve over
the following week despite the fact that they were no longer
taking the capsules. However, about half of this group experienced
the return of some mild arthritic symptoms after about three
to five weeks. (Although not included as part of this study,
all of the subjects in this group were treated again and their
symptoms have not returned.) The patient with reactive psoriatic
arthritis also experienced an almost complete reversal of
his associated very severe psoriatic skin condition affecting
about 20% of his total skin area.
GROUP # 2: Severe to crippling
rheumatoid arthritis
In Group #2, nine subjects
presenting with severe to crippling rheumatoid arthritis were
supplied with 50 capsules to be taken in two series, two 75mg
capsules each morning and evening for seven days, with a seven
day interval before repeating the same dosage for 5-1/2 more
days. Four of these subjects were unable to walk and were
accustomed to being transported by wheelchairs. One, her femur
being fused at the hip, was unable to achieve a sitting position
for wheelchair transport. She could, however, move about slowly
on crutches as long as she was accompanied by someone to aid
her in maintaining her balance. Otherwise she could only stand
or lie down. The remaining four could move about with canes
or walkers. All nine subjects presented with pain, inflammation,
and marked deformation of nearly all proximal interphalangeal
and large joints. Five presented with limited lumbar flexion
and pain in the vertebral column. All had difficulty grasping
and manipulating common objects.
Within three days of treatment
six subjects in the group reported a 30% to 50% decrease in
pain and 20% to 30% increase in joint mobility, and three
subjects reported little change. Within seven days five subjects
reported a 70% to 90% decrease in pain and 70% to 80% increase
in joint mobility. Three subjects reported to be totally free
of pain with almost complete return of joint mobility and
marked improvement in joint deformation. One patient reported
no perceptible change.
On the fourteenth day, at the
end of the one week interval without treatment, six subjects
reported minor continuing improvement; two reported maintaining
their improved status, and one continued to show no improvement.
Treatment was resumed on the fifteenth day for 5-1/2 more
days.
By the end of the treatment
period all but two subjects reported to be 90% free of pain
with return of 70% to 100% mobility. The fused hip joint remained
fused, of course, but with a return of over 70% mobility in
other joints the subject felt hip surgery now to be worth
consideration. The one non-responsive subject proved to have
cirrhosis of the liver, which may have been the reason for
her inability to respond to treatment.. Further investigation
is necessary to determine the role of liver function in this
protocol.
GROUP # 3: Mild to moderately
severe rheumatoid arthritis
In Group #3, fourteen subjects
presenting with mild to moderately severe rheumatoid arthritis
were supplied with 24 capsules, two 75mg capsules to be taken
each morning and evening for six days. After three days of
treatment eleven reported about 20% to 30% improvement in
articulation and inflammation, and about 40% to 50% relief
of arthritic pain. In these eleven subjects improvement continued
rapidly over the next four days, approaching the 80% to 100%
level. The remaining three subjects reported similar improvements
by the end of the fourth day, with an overall improvement
of 70% to 80% after seven days.
Most of the subjects continued
to report minor additional improvement for one week or more
even though they were no longer under treatment. However,
six in this group began to experience the return of some mild
arthritic symptoms after about three to four weeks. (Although
not included as part of this study, all of the subjects in
this group were treated again and their level of improvement
has subsequently stabilised).
GROUP # 4: Severe to crippling
osteo-arthritis
In Group #4, fourteen subjects
presenting with severe to crippling osteo-arthritis were supplied
with 50 capsules to be taken in two series, two 75mg capsules
each morning and evening for seven days, with a seven day
interval before repeating the same dosage for 5-1/2 more days.
Three of these subjects were unable to walk and were accustomed
to being transported by wheelchairs. The other eleven could
move about with crutches, walkers, or canes. All presented
with pain, inflammation, and marked deformation of nearly
all interphalangeal and large joints. Four presented with
limited lumbar flexion and pain in the vertebral column. Ten
had difficulty grasping and manipulating common objects.
After four days of treatment
ten in this group reported 30% to 50% improvement in articulation
and inflammation and about 40% to 60% relief of arthritic
pain. In these ten subjects improvement continued rapidly
over the next three days, reaching 80% to 100% by the end
of seven days. One reported no perceptible change.
On the fourteenth day, at the
end of the one-week interval without treatment, nine subjects
reported continuing minor improvement, four reported maintaining
their improved status, and one continued to show no improvement.
Treatment was resumed on the fifteenth day for 5-1/2 more
days.
By the end of the treatment
period eleven subjects reported 80% to 100% relief of pain
with a return of 80% to 100% mobility. Two subjects reported
70% to 80% return of articular mobility with a 70% to 90%
reduction of arthritic pain. The one non- responsive subject
proved to have previous liver damage as a result of sports-related
steroid abuse. Further studies are necessary to determine
the role of liver function in this protocol.
SUMMARY
The results of this study lead
to several conclusions regarding its five principal objectives:
-
Optimum dosage levels appear to be equal
for all three types of arthritis investigated: osteo-arthritis,
rheumatoid arthritis, and reactive psoriatic arthritis.
This is evidenced by the gradual return of minor arthritis
symptoms in several of those treated with only 16 or 24
capsules, and no regression in those treated with 50 capsules
in two series separated by one week without treatment.
-
Dosage level requirements appear to be equal
irrespective of the severity of the subject's condition.
-
Initial response time for minor improvement
appears to vary from two to seven days irrespective of
the severity of the subject's condition.
-
The time for maximum attainable response
appears to vary from seven to twenty-one days, resulting
in 70% to 100% overall improvement. (Apart from this study,
three of the most severely afflicted subjects were treated
again after a five-week interval, resulting in an additional
10% to 20% overall improvement.)
-
The two non-responding subjects both proved
to have suffered previous damage to the liver from steroid
or alcohol abuse, indicating that impaired liver function
may preclude success with this protocol.
In addition, it was evident
that for many subjects the relief of inflammation resulted
in marked improvement in joint deformation.
(This study was conducted at
several different sites after the model prepared by the San
Diego Clinic.)
CASE HISTORIES
Here are some condensed case
highlights from The San Diego Clinic Trials
From case history #38: Medical
Doctor. Pain and stiffness in hands for several years. Unable
to perform simple office surgery. One day of CMO brought relief.
Dexterity and fine surgical ability returned gradually. Ordered
CMO for his patients.
From case history #39: Male.
Medical Doctor/psychiatrist. This physician complained of
persistent pains along his spine and in his feet. He became
completely free of pain in both the spine and feet within
two days of starting CMO capsules. Remission continues.
From case history # 33: Medical
Doctor. Auto wreck ten years earlier damaged hip, caused limp
and arthritis. CMO relieved pain permanently in one day for
the first time after many years. The limp problem is irreparable.
Ordered CMO for his patients.
From case history # 06: Female.
Age 45. Arthritis attack worsened rapidly over a period of
only seven months. Required a wheelchair to be moved about.
Frequently unable to leave bed in mornings because of debilitating
pain. Seeking relief, she worked with a personal trainer.
She was incapable of holding a five pound weight, unable to
make a fist. Saw immediate improvement with CMO in just three
days. Two weeks after the first, she took a second course
of CMO. She is now able to perform a full workout, has no
difficulty making a fist, wakes in the mornings free of pain,
and has resumed a normal active life.
From case history # 29: Female.
Age 63. Despite devoted adherence to a truly natural diet,
suffered severe osteo-arthritis in most joints for over ten
years. Woke to agonising pain. Even simple chores were arduous.
CMO brought total relief in ten days.
From case history # 24: Female.
Age 50. Family history of arthritis. Pain in shoulders. Severe
pain, limited mobility, and gross swelling in hands and fingers.
By the third day of CMO, hands were free of pain, mobility
had increased immensely, and finger swelling decreased so
dramatically she had to have all her rings re-sized. Repeated
treatment three weeks later. Totally free of pain and inflammation
since. For the first time in many years, she was recently
delighted to experience a pain-free skiing holiday.
From case history # 22: Female.
Clinically obese. Arthritis in neck and spinal column resulting
in joint mobility limitations. Despite impaired liver function
which frequently inhibits the benefits of CMO, her range of
motion increased by 100% within one week. A repeat course
of CMO two weeks later has resulted in even greater and continuing
improvement.
From case history # 03: Male.
Age 32. Rheumatoid arthritis at age 25. Family history of
arthritis. Seven years of pain in hands, shoulders, legs,
and ankles. Although subject saw substantial improvement after
taking CMO for three days, he did not experience complete
relief with continuing remission for about two weeks. He has
subsequently enjoyed skiing holidays and has been able to
return to playing golf without the discomfort of any pain
From case history # 17: Female.
Age 60. Physician. Relentless pain from hip injury one year
prior. Diverse treatments and medicines brought little relief.
With CMO and massages to reduce edema and improve muscle activity,
her pain gradually diminished in two weeks. Now remains completely
free of pain.
From case history # 15: Lifelong
athlete. Arthritic pain and/or stiffness in hands, feet, knees,
neck, and shoulders _ especially with exposure to the cold.
With three days of CMO, was totally free of pain with dramatically
increased articulation in the joints. Further improved mobility
came with a repeat set of CMO three weeks later. He now enjoys
skiing and other activities with the vigour and delight he
lost so many years ago.
From case history # 11: Male.
Age 58. Ex football player. Clinically obese. Had knee surgery
three times about 15 years ago. Had extreme pain upon lying
down. Often slept in a recliner chair instead. With his first
evening dose of CMO capsules, he slept soundly and arose the
next morning completely free of pain. He has enjoyed continuing
pain-free remission ever since the first day.
From case history # 08: Male.
Medical Doctor/psychiatrist. Pains in feet daily for over
five years. With CMO almost constant pain disappeared within
a day. Ordered CMO for his patients.
From case history #32:
Female. Age 66. Rheumatoid arthritis rendered hands useless,
gnarled, inflexible, agonisingly painful six years ago. Pain
relieved and full use of hands restored after five days of
CMO.
