Hypothesis"HomeNewsContact UsOrder OnlineProductsTestimonialsFAQsResearchBrochureAdvertisementsRetailersAbout UsPantothenic 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 Orthromolecular 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.
© 1999 Coenzyme-A Tech. Inc. All rights reserved.
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