Because P.acnes may contribute
to an inflammatory response, but in 99% of the cases, it is not the cause
of our initial
Please review the following exercept from:
ACNE DIET, CLEANSING & LEAKY GUT SYNDROME RESOURCE GUIDE
(perhaps one day I'll finish this, LOL)
Chronic Silent Inflammation
Acne is an Inflammatory Skin Disease
Please do not let this title deter you from thinking that acne is not genetic, that acne is not hormonal, that acne is not a form of skin diabetes, etc. These are ALL true...it's just that currently the evidence points to what's activating the acne, causing the hormonal disorder, skin diabetes, insulin resistance, etc is due to Subclinical
(no obvious outward signs) Long-term Inflammation
Ever wondered why certain drugs are prescribed for acne?
Why Accutane or Antibiotics are probably the most prescribed methods of treatment for acne sufferers?
Ever wonder why if acne is caused by a bacteria, why you would be prescibed Accutane, or Spironolactone or Birth Control, when NONE of these kill bacteria?
Ever wondered if the problem has to do with androgens, WHY are the dermatologists still prescibing antibiotics....long-term?
Acne has been called an Inflammatory Skin Disease
for decades. Based on available articles, science and the medical community have known about some of these immunological events preceeding two specific immune responses (Type III & Type IV) which initiate the inflammatory events found in the development of acne since the 1970s!
As a response to this inflammation, antibiotics was chosen as one of the first methods to fight against this in acne
Unfortunately, due to the past and present mindset of certain doctors and scientists, a percentage of us are worse off because of it either mentally
(people still think it's about bacteria or sebum) or at least physically
, thanks to developing some of the known side effects of antibiotics.
Now, after reading numerous scientific articles/abstracts what I've noticed is that antibiotics do indeed work to kill certain types of inflammation. Antibiotics are used:
To kill the inflammation that clogged the pores and then to kill the inflammation caused by overgrown TRAPPED bacteria!
This is why it's continually prescribed for acne, except these SAME sources of inflammation can be inhibited or prevented, in acne sufferers, by using:
* Anti-fungals (and they don't kill p.acnes)
* Green, White, Red Tea
* among other HIGH powered antioxidants
Not to mention, this includes a host of other drugs or topicals used in the treatment of acne. Omega 3s
are obviously anti-inflammatory. AHAs
(Glycolic, Mandelic, etc) are anti-inflammatories. Salicylic Acid/BHA
is an anti-inflammtory. Retinoids
are anti-inflammatories. Benzoyl Peroxide
is an anti-inflammatory. Hydrocortisone and Glucocorticoids (to a point) are anti-inflammatory. Tylenol
, & Motrin
which some members use (and SHOULDN'T) are anti-inflammatories. B5 Therapy
The list goes on, some do it directly
and others indirectly
by inhibiting or regulating
our ability, in some way, to make inflammatory products! Most of these drugs, topicals, supplements, as well as specialized diets also have other abilities and due to this, or the fact that some have stronger anti-inflammatory properties, make certain "treatments" a better choice than other methods based on an individuals circumstances.
Now, the above list of supplements, which are usually antioxidants, and some of these drugs, and certain diets, can multitask
by lowering our testosterone levels, our IGF-1 levels, and boosting our Glutathione Levels, or SOD levels, and our PGE1 Anti-inflammatory Prostaglandins, among other things.
Chronic inflammation can cause biochemical imbalances and those biochemical imbalances can cause (further) inflammation!
When I speak of inflammation, with regards to acne sufferers, I'm referring to biomolecules such as:
* Free Radicals
* ROS - Reactive Oxygen Species
* PGE2- Proinflammatory Prostaglandins
* Leukotriene B4
* Cytokines (Interleukines 1 - 12a/b sometimes, TNF-a/Tumor Necrosis Factor-a, etc)
* NO - Nitric Oxide
* Peroxide (from lysed PMN/Polymorphonuclear leukocytes (white blood cells/neutrophils))
* Lactic Acid
* PPAR beta/delta - Peroxisome Proliferator Activated Receptors beta/delta
* Substance P
Like for me to back up back up my statements? Read on!
Skinmed. 2003 Jul-Aug;2(4):222-8. Related Articles, Links
Assessment of etiologic agents in acne pathogenesis.
Burkhart CN, Gottwald L.
The Department of Microbiology, Medical College of Ohio at Toledo, Toledo, OH 43623, USA. [email protected]
Acne is a chronic inflammatory disease
of the pilosebaceous units. Traditional etiologic factors include increased sebum production, ductal hyperkeratosis, abnormality of the microbial flora within the pilosebaceous unit, and mediators of inflammation. Recent developments do not refute these familial elements, but rather refine particular aspects. Interleukin-1a
of the infundibulum as well as the inflammatory response
by inducing the production of vascular endothelial growth factor in dermal papilla cells and follicular keratinocytes of the pilosebaceous unit. New retinoids have been developed based on controlling cellular proliferation and differentiation in the pilosebaceous unit by their action on nuclear receptors of cells. Dermal inflammation is not due to presence of bacteria, but from biologically active mediators produced by Propionibacterium acnes
. The environment
within the pilosebaceous unit is probably more important
than the absolute number of P. acnes organisms. Indeed, the major role of the sebaceous gland appears to be supplying P. acnes needed nutrients.
Moreover, the microbiologic principle of biofilms appears to be applicable to P. acnes in acne.
(Thankfully further studies refine THIS study as well)
Rev Med Chir Soc Med Nat Iasi. 2004 Apr-Jun;108(2):319-24. Related Articles, Links
[Immunohistochemical evidence of chronic inflammation in acne vulgaris]
[Article in Romanian]
Branisteanu D, Cianga C, Cianga P, Petrescu Z, Carasevici E.
Universitatea de Medicina si Farmacie Gr.T. Popa Iasi, Facultatea de Medicina, Clinica Dermatologica.
The etiology and pathogenesis of acne vulgaris are not yet completely understood. Therefore we have investigated 5 patients with different clinical forms of disease, including the rare form of acne fulminans.
Taking into consideration the four factors that are currently incriminated in the development of acne, sebaceous hypersecretion, hyperkeratosis of the pilosebaceous infundibulum, bacterial colonisation and perifollicular inflammation, we have focused our study on a set of cells involved in the chronic inflammatory process
. We have evidenced by immunohistochemistry methods, using appropriate monoclonal antibodies, the presence of T lymphocytes and macrophages, while the B cells could be evidenced only in the severe forms.
We were also interested to investigate the occurrence of new capillary formation, as an accompanying phenomenon of the inflammatory process. The presence and histological distribution of these cells highly supports the hypothesis that the mechanisms underlying the development of acne vulgaris belong to the Delayed Type Hypersensitivity
PMID: 15688807 http://www.ncbi.nlm....l=pubmed_docsum
(This was one I had been looking to post again for awhile and I thought they had removed this article! This is a Type IV Hypersensitivity Reaction and was a key part of my arguement for WHY, sometimes, there's such a huge variance among the anti-inflammatory/anti-acne diets.)
Acta Dermatovenerol Alp Panonica Adriat. 2005 Jun;14(2):39-42. Related Articles, Links
Superoxide dismutase and myeloperoxidase activities in polymorphonuclear leukocytes in acne vulgaris.
Kurutas EB, Arican O, Sasmaz S.
KSU Medical Faculty, Department of Biochemistry, TR-46000 Kahramanmaras, Turkey.
BACKGROUND AND DESIGN: Acne vulgaris frequently occurs in the second decade of life. The pathogenesis of the disease is multifactorial and in the present study, we aimed to investigate the role of reactive oxygen species
in the inflammation of acne by determining the activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) in polymorphonuclear leukocytes (PMN).
MATERIALS AND METHODS: Forty-three patients with acne vulgaris and 24 healthy controls were enrolled. The severity of the acne was categorized from mild (subjects with only comedonic lesions) to severe (subjects with nodulocystic lesions). SOD and MPO activities in PMN were measured spectrophotometrically.
RESULTS: There was no significant difference in the activity of MPO between the patients and controls.However, SOD activity in PMN was significantly lower in the patients
than in the controls (p<0.001). Nocorrelation was detected between the activities of enzymes and the severity of the disease.
CONCLUSION: Propionibacterium acnes may not play a primary role in the pathogenesis of acne as a bacterium.
However, the low activity of SOD in PMN may be responsible for the increased levels of superoxide anion radicals in the epidermis. New anti-acne drugs should include substances with lymphocyte stimulating and anti-oxidative properties.
PMID: 16001098 [PubMed - indexed for MEDLINE]
And excerpts from "What is the pathogenesis for acne?"
Zouboulis CC, Eady A, Philpott M, Goldsmith LA, Orfanos C, Cunliffe WC
Rosenfield R. What is the pathogenesis of acne?
Exp Dermatol 2005: 14: 143Ã¢â‚¬â€œ152. # Blackwell Munksgaard, 2005
Abstract: For a long time, the mantra of acne pathogenesis debates has been that
acne vulgaris lesions develop when (supposedly largely androgen-mediated)
increased sebum production, ductal hypercornification, and propionibacteria come
together with local inflammatory process in the unlucky affected individual. And
yet, the exact sequence, precise interdependence, and choreography of pathogenic
events in acne, especially the Ã¢â‚¬Ëœmatch that lights the fireÃ¢â‚¬â„¢ have remained surprisingly
unclear, despite the venerable tradition of acne research over the past century.
However, exciting recent progress in this Ã¢â‚¬â€œ conceptually long somewhat stagnant, yet
clinically, psychologically, and socioeconomically highly relevant Ã¢â‚¬â€œ everyday battlefield
of skin pathology encourages one to critically revisit conventional concepts of acne
pathogenesis. Also, this provides a good opportunity for defining more sharply key
open questions and intriguing acne characteritics whose underlying biological basis has
far too long remained uninvestigated, and to emphasize promising new acne research
avenues off-the-beaten-track Ã¢â‚¬â€œ in the hope of promoting the corresponding
development of innovative strategies for acne management.
Inflammatory signalling is involved in the initiation
(Funny Splenda/Sucralose is a Chlorinated/Halogenated Polycyclic Aromatic Hydrocarbon (LabGirl, True or False) and based on reports on this board as well as on the web, just as with Dioxin, it is capable of increasing acne in those prone and initiating acne in those not prone.)
of acne lesions
Hyperproliferation of the follicular epithelium leads to formation
of microcomedones, which are the first acne lesions and
can be found in normal-looking skin
(23). The sebaceous
follicle undergoes a cycling process which may explain a natural
resolution of microcomedones and also comedones and,
on a longer term, the resolution of the disease itself (24)
(Fig. 1). The very early stage of acne lesion development,
namely the beginning of microcomedones, is associated with
vascular endothelial-cell activation and involvement of inflammatory
events (25) which corroborates the suggestion that acne
may represent a genuine inflammatory disorder without involvement
of bacteria in its initiation
Similar results have been reported by Ingham et al. (27) who found bioactive interleukin
(IL)-1a-like material in the majority of open acne comedones
from untreated acne patients. There was no correlation
between levels of any cytokine, in particular IL-1a, and the
numbers of follicular microorganisms.
It seems that healthy
sebaceous glands also express various cytokines. In our laboratories,
we stressed sebocytes in vitro by maintaining them in
serum-free medium and detected IL-1a expression at the
mRNA and protein levels
(28). Antilla et al. (29) showed that
IL-1 is present in normal sebaceous glands and Boehm et al.
(30) detected mRNA for IL-1a
and tumor necrosis
in normal sebaceous glands by in situ hybridization.
Interestingly, IL-1a induced hyperproliferation of follicular
keratinocytes in isolated sebaceous follicle infundibula maintained
ex vivo (31).
Which factors interrupt cycling of the sebaceous
Overstimulation of the initiation of the preclinical inflammatory
process or defect negative feedback regulation may be major
reasons for the interruption of the normal cycling of the sebaceous
follicle and be responsible for the initiation of the clinical
inflammatory process in acne (Fig. 1). As mentioned above, hereditary
factors and excess androgen activity, e.g. in puberty, may
cause overstimulation, thus triggering sterile inflammatory phenomena
(Fig. 2). Neuroendocrinologic regulation and environmental
factors, such as dietary lipids and smoking, have also
been suggested to represent trigger mechanisms
Role of neuropeptides for regulation of clinical
inflammation in acne
There is current evidence that regulatory neuropeptides with
hormonal and non-hormonal activity may control the development
of clinical inflammation in acne. Numerous substance P
immunoreactive nerve fibers were detected in close apposition to
the sebaceous glands, and expression of the substance P-inactivating
enzyme neutral endopeptidase
was observed within sebaceous
germinative cells of acne patients (32). In vitro experiments
using an organ culture system demonstrated that substance P induced
expression of neutral endopeptidase in sebaceous glands
in a dose-dependent manner. On the other hand, treatment of
sebocytes with IL-1b which resulted in marked increase of IL-8
release (33) was partially blocked by co-incubation of the cells
with a-melanocyte-stimulating hormone in a dose-dependent
manner (34). Corticotrophin-releasing hormone
synthesis of sebaceous lipids in vitro (33), and adrenocorticotropic
evokes adrenal dehydroepiandrosterone
[DHEA androgen] to regulate skin
inflammation (35). These current findings indicate that central
(36) or topical stress (33,37) may, indeed, influence the feedback
regulation, thus inducing the development of clinical inflammation
in early acne lesions
Dietary lipids and inflammatory process in acne
Topically applied linoleic acid
was shown to induce an almost
25% reduction in the overall size of microcomedones over a
1-month treatment period
(38). On the other hand, arachidonic
acid, an essential, long-chain, pro-inflammatory o-6 fatty acid,
stimulates IL-8 and IL-6 synthesis in cultured human sebocytes
(39) and enhances synthesis of sebaceous lipids
B4 inhibition in vivo reduces concomitantly pro-inflammatory
sebaceous fatty acids and inflammatory acne lesions (22).
Eskimos, the inhabitants of the Okinawa island and Chinese have
been observed to develop acne with the changing of their nutrition
habits (20,40,41). Westernized nutrition includes low
amounts of o-3-fatty acids and antioxidant vitamins and higher
amounts of the pro-inflammatory o-6 and trans-fatty acids. The
ratio o-6/o-3 fatty acids in westernized nutrition is 20 : 1, in
contrast to a 1 : 1 ratio in traditional nutrition
Overall, the role of nutrition in acne still remains controversial. A
current study reported that the Kitavan islanders of Papua New
Guinea and the Ache hunter-gatherers of Paraguay do not present
acne (43), however, other authors suggested that these population
studies may have detected a genetic background rather than a nutritional
Smoking and acne
Smoking was currently reported to be a clinically important
contributor to acne prevalence and severity (45). Recent investigations
revealed that cigarette smoke contains high amounts of
and polycyclic aromatic hydrocarbons
induce a phospholipase A2-dependent inflammatory pathway
(46); this effect may further stimulate arachidonic acid synthesis
(37). On the other hand, smokers have a higher saturated fat
intake with their food and much lower polyunsaturated fat
intake, principally due to a lower linoleic acid intake compared
Are Propionibacterium acnes (P. acnes) and tolllike
receptors involved in the initiation of acne
Toll-like receptors 2 and 4 as well as CD14 are expressed in
human monocytes. Chemokine/cytokine synthesis in these cells
is induced through activation of Toll-like receptor 2 by P. acnes
(48). These findings in combination with the expression of active
Toll-like receptors 2 and 4 and of CD14 in human keratinocytes
(49) have implicated P. acnes and Toll-like receptors in acne
inflammation. However, P. acnes was unable to induce IL-1a
expression in human keratinocytes in vitro (50), therefore,
P. acnes seems to induce later events not being involved in
the initiation of acne lesions.
The successful therapeutic
action of antibiotics
in acne has been attributed to an antibacterial
activity but it may also be seen as a para-antibiotic,
is likely to be a genuine inflammatory disease
, PPAR ligands
, regulatory neuropeptides
, and environmental
being agents able to interrupt
cycling of the sebaceous follicles and lead microcomedones to
form comedones and inflammatory lesions
(Figs. 1 and 2). Proinflammatory
lipids and chemokines/cytokines seem to act as
mediators for the initiation of acne lesions. P. acnes is not initially
involved but may mediate later inflammatory events leading to
worsening of the lesions.
This concept of acne pathogenesis may be controversially discussed,
however, it initiates a fruitful discussion for better understanding
this most common disease.
Therefore, while inflammation is at play, it's obvious P.acnes doesn't play a PRIMARY role, otherwise why the use of RetinA, Accutane, Spironolactone, other antiandrogens, anti-fungals, and Insulin Sensitizers (some are PPAR-gammas), etc???
Yes, they all work to kill some aspect of the inflammatory process, which in turn, or in conjunction, allows them to also regulate blood sugar, regulate androgen production, regulate IGF-1 production, etc.
Now, if we can all begin to think
of acne as an inflammatory skin disease first
, and for now everything else about it second, we can move on
to figuring out WHAT
we need to do to trace the source of inflammation and HOW
to stop it!