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Medical
Study by
Dr. Lit-Hung Leung, M.D.
Pantothenic
Acid in the Treatment of Acne Vulgaris
"A
Medical Hypothesis"
by
Lit-Hung Leung, M.D.
This article originally appeared in the scientifically prestigious
Journal of Orthomolecular Medicine Vol. 12 Number 2, 1997. The
version below is from a reprint of the original article and
revisions were made in December 1998.
The Pathogenesis of Acne Vulgaris: A Medical Hypothesis
Over the years the pathogenesis of acne vulgaris has been extensively
studied including, the structure and function of the pilosebaceous
follicle, the physiology of sebum, microflora in acne vulgaris,
and abnormal follicular keratinization, considered to be one
of the earliest events in acne formation. Despite the concerted
effort of many scientists, internists, pathologists and dermatologists,
the pathogenesis of acne vulgaris remains largely elusive.
In this paper, I would like to approach this problem from a
different perspective. My clinical observations suggest that
acne vulgaris may be closely related to the consumption of diets,
which are rich in fat content. This impression is by no means
novel. Textbooks do briefly mention this correlation though,
more often than not, it is dismissed as irrelevant. However,
my observations have led to quite the contrary conclusions.
Not only is the fat content of food closely related to acne
vulgaris but it forms some sort of linear relationship with
the disease process. The more fat the patient consumes, the
more severe will be the acne process. This observation is in
line with the opinion of many dermatologists that chocolate,
which is composed mainly of the creamy part of milk, and has
a high degree of fat content, is bad for acne. Significantly,
in this group of patients, any deliberate attempt in trying
to avoid a fatty diet over a period of weeks, if not days, will
often result in important compound, cholesterol, which in turn
is basically synthesized from units of acetyl-CoA. In the synthetic
process, the body naturally is always trying not only to reach
for a normal level of androgens, but an optimal level, so as
to allow the body to function at its best. However, this is
not always possible, and the normal level reached may not represent
the optimal level. This is natures flexible way of dealing with
shortage of essential dietary elements in any form to achieve
a level that is just enough to manage the present situation,
leaving a variable degree of shortage from the optimal level.
In the present instance, in the two groups of boys, one group
may have a normal level of androgens that is falling short of
the optimum. One possible explanation for this is that there
is a lack of basic building blocks, the acetyl-CoAs, which deter
the body from operating at peak efficiency. If this is a viable
possibility, it suggests that a plentiful supply or a deficiency
of acetyl-CoA in the body may play a role in the acne process.
this is certainly possible. Aside from its role in the synthesis
of the sex hormones, acetyl-CoA, of which Coenzyme-A is the
important component, it is also important in fatty acid metabolism
as an acyl carrier in the lengthening and degradation of long
chain fatty acids by adding or removing acyl groups in the metabolic
process.
Acne vulgaris is related to lipid metabolism as well as the
sex hormones, both of which have a lot to do with Coenzyme-A.
This relationship provides a reasonable ground to link up the
acne process to Coenzyme-A and to investigate the pathogenesis
of acne vulgaris along this line.
The Importance of Coenzyme-A
In trying to link acne vulgaris to Coenzyme-A, it is important
to have a hypothesis supporting some basic facts. A closer look
at Coenzyme-A may provide the evidence.
A Sharing scenario; As a coenzyme active in both fatty acid
metabolism and sex hormone synthesis, Coenzyme-A is shared between
two different metabolic processes. This is not uncommon in biochemical
reactions in metabolism, where a coenzyme is often shared among
a number of reactions. Coenzyme-A is arguably the most important
coenzyme in the body, and when a coenzyme is involved in the
metabolic process to such an extent as this, it becomes legitimate
to ask if a shortage and deficiency is possible. To answer this,
a brief look at the structure of Coenzyme-A is warranted.
Coenzyme-A is formed from adenosine triphosphate, cysteine,
and pantothenic acid. Of these pantothenic acid is the only
component that is a vitamin, and must be provided from our dietary
intake. Could there be an insufficient intake of pantothenic
acid resulting in a deficiency in Coenzyme-A, which would leave
the body unable to cope with all the reactions, that it has
to perform with that all-important coenzyme? Conventional wisdom
does not think so. It is suggested that pantothenic acid, being
ubiquitous, can be had from whatever kind of food that is taken
in, and that there is no question as to its deficiency in our
body. However, a deficiency is still possible. After all, when
so many reactions are dependent on the same agent, its demand
must be tremendous. Shortage under such circumstances is not
entirely impossible.
The Crucial Question and the New Theory
If the question of deficiency of Coenzyme-A does come up, how
does it affect acne, knowing its importance in fatty acid metabolism
and sex hormone synthesis? This is the crucial question. This
is where the new hypothesis on the pathogenesis of acne vulgaris
is based, and this is where it diverges from conventional medical
ideas. The author's proposed hypothesis for the pathogenesis
of acne vulgaris is that the disease process is not caused by
androgens, or any other sex hormones, but rather, the disease
process results from a defect in lipid metabolism that is secondary
to a deficiency in pantothenic acid, hence Coenzyme-A. Coenzyme-A,
in carrying out its function efficiently both as an agent in
fatty acid metabolism and an agent in androgen and sex hormone
synthesis, has to be present in sufficient amounts, and anything
less than sufficient will result in some compromise.
Mother Nature's Choice
Faced with the dilemma of a shortage of Coenzyme-A the body
will tend to make a choice that is to the best advantage of
the individual. The body does so by largely maintaining the
functionally more important reaction, while at the same time
slowing down the lesser important one. The choice here is a
relatively simple one. Nature will seek to take care of the
synthesis of hormones first, because continuation of the species
depends on the development of the sex organs. Fatty acid metabolism
is, for the time being, at least in part halted. Lipids start
to accumulate in the sebaceous glands, sebum excretion is increased,
and acne begins to appear. When there is enough Coenzyme-A in
the body, however, both reactions will be well taken care of.
There are enough sex hormones for the sex organs to develop.
The lipids in the sebaceous glands are completely metabolized
by sufficient Coenzyme-A, and there will be no unwanted lipid
in the glands and little sebum will be excreted to cause acne
vulgaris.
The Mystery Revealed
The mechanism proposed above may be the reason why two groups
of adolescent boys both with a normal blood level of androgen
may exhibit differences in the incidence of acne. The group
with acne is the one that has not enough pantothenic acid in
the body, whereas in the other group, pantothenic acid levels
are not deficient.
This new theory seems to work well here, and can be tested in
other metabolic situations. In the case in which endogenous
androgen stimulates acne, whereas exogenous does not, the reasoning
for the observation is the same. Any endogenous androgen synthesis
will require the participation of extra amount of pantothenic
acid. This will channel off some of those that are doing the
work of fatty acid metabolism. Consequently, fatty acid metabolism
becomes less efficient and the individual is more prone to have
acne.
Today, the percentage of adult women that have acne is increasing.
Some of these women may not have had acne as teenagers, and
are surprised to find that they have to deal with this unpleasant
problem during their adult years. Acne can have profound psychological
and social effects on adults, just as it does in teenagers.
Many women in their 30s and 40s experience high levels of life
stress because they shoulder the multiple burdens of career,
child rearing, and housework, and often the responsibility of
caring for their own aging parents. Perhaps this increasing
level of stress has contributed to the rising incidence of acne
in adult women.
Microcomedo
Acne vulgaris of adulthood is similar to teenage acne. The pilosebaceous
units of the face, chest, and back can be involved. The primary
lesion of acne is the "microcomedo." A microscopic plug develops
due to the presence of thickened and impacted keratin (dead
cells) and excess oil production (sebum). More and more of the
keratin and sebum back up behind this plug and form a distended
follicular pore. This results in either an open comedo (blackhead)
or a closed comedo (whitehead). The enlarged pilosebaceous structure
allows Propionibacterium acne's, an anaerobic diphtheroid, to
proliferate. Propionibacterium acne's contributes to the breakdown
of lipids to free fatty acids, which are highly inflammatory.
The distended follicle can rupture, causing further inflammation
and the development of papules, pustules and nodules.
Acne Rosacea
Another skin disease that simulates and can coexist with acne
vulgaris is acne rosacea. This skin problem is common in women,
most often between the ages of 30 and 50. The face, especially
the middle third, is erythematous and flushed. Multiple telangiectasias
are frequently present. Small papules and pustules, which may
look similar to those seen in acne vulgaris, are common, but
the microcomedo component of acne vulgaris is absent in blepharitis.
Rosacea keratitis is less common, but potentially vision-threatening.
Rosacea is another skin disorder that is frequently stress related.
What about premenstrual flare? In the luteal phase of the menstrual
cycle, progesterone in is secreted abundantly by the corpus
lutcum. This naturally will take up a lot of pantothenic acid
from the body's pantothenic pool leading to a re-distribution
of the vitamin and putting enormous pressure on fatty acid metabolism.
When this metabolic process is not performing satisfactorily,
lipid begins to accumulate in the sebaccous glands, an increase
in sebum is excreted, and acne follows. That is why even thought
progesterone has no effect on sebaceous gland activity, an increasing
level of progesterone in the late stage of the luteal phase
leaves the acne patient with a prominent flare.
Similarly, this may explain why eunuchs rarely exhibit acne.
Since so few sex hormones are secreted, the pantothenic acid
pool can deploy a more significant portion of its reserve to
metabolize fatty acids. When this is efficiently done, little
sebum is excreted, and no acne is formed.
This theory also explains the paradoxical problem of equal sex
hormones that counts. Both males and females need sex hormones
for the development of sex organs and the secondary sexual characteristics.
The only difference is that in the male, the female sex hormones
predominate. Apparently the synthesis of sex hormones uses a
large portion of the pantothenic acid pool, leaning a relative
shortage of it to efficiently metabolize fatty acids. The result
is that acne starts to erupt, at the same time the sex organs
begin to develop at puberty.
The reason acne first erupts at puberty is not, therefore, endocrinological,
but rather secondary to the deployment of a substantial amount
of pantothenic acid for the purposes of synthesis of sex hormones,
leaving a relative deficiency for fatty acid metabolism. The
size of this pantothenic acid pool and the ability with which
the individual can deploy reserves from the pool varies and
is likely to be influenced by genetic and dietary factors.
In conditions in which there is an increase in secretion of
any hormone whose synthesis requires the participation of pantothenic
acid, acne may erupt. This is frequently seen with those hormone
secreting tumours of the ovary, testis and the adrenals. The
rapid decline in incidence of acne after adolescence can also
be explained. After the sex organs are fully developed, less
sex hormones are required, leaving an adequate supply of pantothenic
acid to serve the function of fatty acid metabolism. When this
function is efficiently accomplished, sebum secretion dries
up, and acne starts to fade.
Deficiency in Lipid Metabolism
In linking the pathogenesis of acne vulgaris to a deficiency
in lipid metabolism and pantothenic acid, it is worthwhile to
remember that fatty acid metabolism is not the sole domain of
pantothenic acid. There are some other essential dietary factors
that are also of importance in the same process. Together they
form a system that will make the whole metabolic process as
efficient as possible. Preliminary studies by the author suggest
that, together with pantothenic acid, biotin as well as nicotinamide
help to further improve the therapeutic results. By themselves
alone, they are far less effective in helping acne patients
than with pantothenic acid, and this serves to support the suggestion
that pantothenic acid plays a central role in lipid metabolism.
Lipid metabolism is a complicated process, and is often intertwined
with other metabolic processes, sharing with them common coenzymes
in widely different reactions. When there is an increase in
level of some of these coenzymes, there may be a shift in the
directions of some ongoing reactions, and may affect lipid metabolism
as a result. This can manifest clinically as acne vulgaris.
To illustrate this, there are reports showing that acne may
be induced by administration of large doses of vitamin B12 alone
or in combination with B6. Cessation of the administration of
these vitamins will bring a halt to the acne eruptions. If the
body is in a relative deficiency state in B6 and B12, administration
of the vitamins will enhance the reactions that involve the
participation of these vitamins. This will set up a chain of
events, some of which entail the participation of pantothenic
acid. With the total pantothenic acid pool fixed relative to
an increase in other vitamins, emphasis of any reaction involving
pantothenic acid will automatically mean a cutting back on other
reactions that require it as a coenzyme. This will often include
those involving lipid metabolism, resulting in a certain degree
of deficiency in that metabolic process, hence the increased
incidence of acne vulgaris in these studies.
Stress Related Acne
It is perhaps relevant here to consider stress as another common
factor that is known to affect acne adversely. Stress in many
forms poses as an aggravating factor in acne lesions. Lack of
sleep at night, pre-examination tension, any psychological problem
that may worry the patient will bring on new acne lesions. To
understand this, one should recall that in combating stress,
the body will secrete glucocorticoids from the adrenal glands
as a means to adapt to stress, what is commonly known as the
fight-or-flight reaction. The glucocorticoids, like the sex
hormones, are derivatives of cholesterol, and increased demand
for this hormone will draw on the pantothenic acid pool. Lipid
metabolism may therefore be compromised, rendering the body
more prone to acne.
If pantothenic acid deficiency is indeed the main causative
agent in the pathogenesis of acne vulgaris, it is logical to
ask how much pantothecic acid patients are lacking in absolute
amounts.
Deficiency Syndromes
Nutritional requirements can rarely be met through a well balanced
diet, and dietary supplements, including vitamins, are often
required. It is the generally held belief of the medical profession
that vitamins, though essential to life and not synthesized
in the body, are not required in great amounts. This view was
challenged, notably by Linus Pauling. In his book, How to Live
Longer and Feel Better, Pauling provided vigorous proof, through
comparative studies in animals and from an evolutionary point
of view, that vitamin C supplements are needed if an optimal
state of health is to be achieved. Not only is supplementation
necessary, gut the amount required is far greater than most
people believe, as with the case of vitamin C where the optimal
dose may be 10 or more grams a day. This issue was a point of
heated debate in the 1970s and 1980s.
Though Pauling has quite a large following, by and large, the
issue was dismissed by the mainstream medical profession, because
of a lack of theoretical support and a general bias against
nutritional and vitamin therapy. But, in view of the new evidence
suggested in thes and many other papers, it seems appropriate
that the issue be considered.
How Much Pantothenic Acid?
In trying to determine the amount of pantothinic acid necessary
to relieve acne patients of their symptoms, Pauling's experience
with vitamin C provides a good guideline. Pauling had for a
long time recommended vitamin C in high dosages to achieve optimal
health. Radically different from what is recommended by the
Food and Nutrition Board of the National Research Council (who
recommended 60 mg daily). Pauling's recommended daily intake
of vitamin C amounts to several grams a day. The recommendation
was stepped up to 15-20 grams a day in his later years. Using
these recommendations as a background, it becomes somewhat easier
to arrive at a proper dosage for pantothentic acid in the treatment
of acne vulgaris.
Pantothenic acid, which acquires its name from the Greek word
meaning ubiquitous, is present in all tissues. Its universal
presence is an indication of its importance. This is further
reflected by the many reactions that it catalyzes. It should
not come as a surprise then, that the amount of pantothenic
acid required for optimal health, is of the same order of that
of vitamin C. Based on this argument, the dose of pantothenic
acid administered to the acne patients was up to 10 grams a
day, and the result of these studies were first reported in
Medical Hypotheses.
The Effect of Pantothenic Acid on Acne Vulgaris
One hundred patients of Chinese descent were included in the
study, 45 males and 55 females. The age ranged from 10 to 30,
and with about 80% between 13 and 23. The severity of the disease
process varied. They were given 10 grams of pantothenic acid
a day in four divided doses. To enhance the effect, the patients
were also asked to apply a cream consisting of 20% by weight
of pantothenic acid to the affected area, four to six tines
a day. With this treatment regimen, the response is as prompt
as it is impressive. There is a noticeable decrease in sebum
secretion on the face usually 2-3 days after initiation of therapy.
The face becomes less oily. After two weeks, existing lesions
start to regress while the rate of eruption of new acne lesions
begins to slow down. In cases with moderate severity, the condition
is normally in complete control in about eight weeks, with most
of the lesions gone and new lesions only to erupt occasionally.
In those patients with severe acne lesions, complete control
may take months, sometimes up to six months or longer. In some
of these cases, in order to get a more immediate response, it
may even be necessary to step up the dose to 15-20 grams a day.
In any event, the improvement is normally a gradual and steady
process, with perhaps minor interruptions by premenstrual flare
or excessive intakes of oily food. With this form of treatment,
another striking feature is the size of the facial skin pore.
The pore size becomes noticeably smaller within one to two weeks,
very often much sooner. Like sebum excretion, the pores will
continue to shrink until the skin becomes much finer, giving
the patient a much more beautiful skin.
This decrease in skin pore size is presumably related to sebum
excretion. When an acne lesion is formed, there is in the epithelial
cell of the hair follicle an accumulation of lipids, leaving
the epithelial cells bulky and the lumen of the gland narrowed.
When there is a concomitant increase in sebum flow, the follicle
has no choice but to hypertrophy to accommodate the changes,
resulting in an enlarged skin pore and coarse skin. With the
administration of pantothenic acid, the whole process is reversed.
Lipid metabolism becomes normal and efficient. The epithelium
is no longer laden with fat droplets, there is a decrease in
sebum excretion, the hypertrophy process is not required. The
skin pores revert to a much smaller size and the skin becomes
smooth and fine.
As acne lesions tend to subside spontaneously after puberty,
some patients do not need a maintenance dose. But, if a patient
is in his mid-teens, when the sexual characteristics have yet
to fully develop, it may be necessary for replacement therapy
to be implemented. This maintenance dose, can be lowered, or
increased with the clinical symptoms. A maintenance dose will
not only act as a preventive measure against sporadic eruption,
but the extra pantothenic acid will help to ease the relative
deficiency state, and likely improve the general health of the
patient.
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