Inflammation, fibros och stress…

“Recent studies have focused on oxidative stress: Naito et al.[23] have recently analyzed the effect of the lipid peroxides on hair follicles, and observed that the topical application of linolein hydroperoxides, one of the lipid peroxides, lead to the early onset of the catagen phase in murine hair cycles. Furthermore, they found that lipid peroxides induced apoptosis of hair follicle cells. They also induced apoptosis in human epidermal keratinocytes by up-regulating apoptosis-related genes. These results indicate that lipid peroxides, which can cause free radicals, induce the apoptosis of hair follicle cells, and this is followed by early onset of the catagen phase. Bahta et al.[24] cultured dermal hair papilla cells (DPC) from balding and nonbalding scalp and demonstrated that balding DPCs grow slower in vitro than nonbalding DPCs. Loss of proliferative capacity of balding DPCs was associated with changes in cell morphology, expression of senescence-associated beta-galactosidase, decreased expression of proliferating cell nuclear antigen and Bmi-1, upregulation of p16 (INK4a)/pRb and nuclear expression of markers of oxidative stress and DNA damage including heat shock protein-27, super oxide dismutase catalase, ataxia-telangiectasia-mutated kinase (ATM), and ATM- and Rad3-related protein. The finding of premature senescence of balding DPC in vitro in association with expression of p16(INK4a)/pRB suggests that balding DPCs are particularly sensitive to environmental stress.

The implication of microscopic follicular inflammation in the pathogenesis of AGA has emerged from several independent studies: An early study referred to an inflammatory infiltrate of activated T cells and macrophages in the upper third of the hair follicles, associated with an enlargement of the follicular dermal sheath composed of collagen bundles (perifollicular fibrosis), in regions of actively progressing alopecia.[25] Horizontal section studies of scalp biopsies indicated that the perifollicular fibrosis is generally mild, consisting of loose, concentric layers of collagen that must be distinguished from cicatricial alopecia.[26] The term ‘microinflammation’ has been proposed, because the process involves a slow, subtle, and indolent course, in contrast to the inflammatory and destructive process in the classical inflammatory scarring alopecias.[27] The significance of these findings has remained controversial. However, morphometric studies in patients with male pattern AGA treated with minoxidil showed that 55% of those with microinflammation had regrowth in response to treatment, in comparison to 77% in those patients without inflammation and fibrosis.[26] Moreover, some forms of primary fibrosing alopecia may represent pathological exaggeration of AGA associated with follicular inflammation and fibrosis, specifically postmenopausal frontal fibrosing alopecia,[28] and fibrosing alopecia in a pattern distribution.”

“one could speculate that microbial toxins or antigens could be involved in the generation of the inflammatory response. Alternatively, keratinocytes themselves may respond to oxidative stress from irritants, pollutants, and UV irradiation, by producing nitric oxide, and by releasing intracellularly stored IL-1α.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929555/

Så i denna studie skriver dem alltså hur oxidativ stress kan bidra till håravfall. Det är massa olika processer inblandade, men i princip så kan inflammation, fibros, och fria radikaler orsaka att hår går in i telogen efflivium, eller så orsakar det apoptosis. Ray Peat förklarar i sin forskning hur bla stress deaktiverar cytochrome oxidase enzymet, vilket är det avgörande enzymet som reagerar direkt med syre i cellers mitochondrier. Cytochrome oxidase är ett enzym som aktiveras av rött ljus (det är genom detta laser fungerar). Det skadas av blått ljus, och fleromättade fetter som skapar fria radikaler. Han pratar även om fibros och hur det uppkommer, men det har jag inte 100% koll på ännu. Han säger även att aspirin, niacinamide och koffein hjälper hår att växa. Alla dessa substanser ökar oxidative ämnesomsättning i mitochondrier. Då celler skapar energi med glukos och syre skapas CO2 som restprodukt. Jag har läst mkt om CO2 på senaste tiden, och kortfattat kan man säga att det är kroppens mest fundamentala substans. Det levererar syre till vävnad, är väldigt bra anti-oxidant skydd, reglerar ph och mineraler. I hypotyreos har man lägre ämnesomsättning och mindre CO2. Många “kroniska” sjukdomar har en sak gemensamt, låg nivå av CO2. Alla stresshormoner är högre vid hypotyreos och vid stress eller felaktig kost, mm. Med andra ord, jag blir mer och mer övertygad om att håravfall kan undvikas om man undviker dessa obalanser, som Peat skriver om.

Physiol Res. 2002;51(4):335-9.

The role of carbon dioxide in free radical reactions of the organism.

Veselá A, Wilhelm J.

Carbon dioxide interacts both with reactive nitrogen species and reactive oxygen species. In the presence of superoxide, NO reacts to form peroxynitrite that reacts with CO2 to give nitrosoperoxycarbonate. This compound rearranges to nitrocarbonate which is prone to further reactions. In an aqueous environment, the most probable reaction is hydrolysis producing carbonate and nitrate. Thus the net effect of CO2 is scavenging of peroxynitrite and prevention of nitration and oxidative damage. However, in a nonpolar environment of membranes, nitrocarbonate undergoes other reactions leading to nitration of proteins and oxidative damage. When NO reacts with oxygen in the absence of superoxide, a nitrating species N2O3 is formed. CO2 interacts with N2O3 to produce a nitrosyl compound that, under physiological pH, is hydrolyzed to nitrous and carbonic acid. In this way, CO2 also prevents nitration reactions. CO2 protects superoxide dismutase against oxidative damage induced by hydrogen peroxide. However, in this reaction carbonate radicals are formed which can propagate the oxidative damage. It was found that hypercapnia in vivo protects against the damaging effects of ischemia or hypoxia. Several mechanisms have been suggested to explain the protective role of CO2 in vivo. The most significant appears to be stabilization of the iron-transferrin complex which prevents the involvement of iron ions in the initiation of free radical reactions.

“This enzyme[Cytochrome oxidase] is dependent upon the thyroid hormone and is inhibited by nitric oxide, carbon monoxide, estrogen, polyunsaturated fatty acids, serotonin, excess or free iron, ionizing radiation, and many toxins, including bacterial endotoxin. Red light, which passes easily through the tissues, reactivates the enzyme, which slowly loses its function during darkness.”

Så att minska alla de här faktorerna är alltså antagligen bra för hår också. Om du kollar studien ovan nämner de både järn och kväve. Järn orsakar mkt oxidativ skada. Rött ljus aktiverar enzymet (laser etc)

“Cytochrome oxidase is one of the enzymes damaged by stress and by blue light, and activated or restored by red light, thyroid, and progesterone. It’s a copper enzyme, so it’s likely to be damaged by excess iron. It is most active when it is associated with a mitochondrial lipid, cardiolipin, that contains saturated palmitic acid; the substitution of polyunsaturated fats lowers its activity. Mitochonrial function in general is poisoned by the unsaturated fats, especially arachidonic acid and DHA.”

“Estrogen (like endotoxin) activates nuclear factor kappa-B (Shyamala and Guiot, 1992; Hamilton, et a!., 2003), which activates cells to produce TNF, nitric oxide, prostaglandins, and interleukins. A long series of observations have indicated that estrogen’s main effects begin with redox changes in the mitochondria, and recent evidence (Felty and Roy, 2005) shows that oxidative free radicals produced in the mitochondria by estrogen induce NF kappa-B…” (prostaglandins har ni hört talas om hoppas jag, väldig känd studie 2013 visade att de påverkade hår. Peat säger att prostaglandiner produceras av pufa, och hämmas av aspirin. Åter igen nämns nitric oxide. NFK-B har också nämnt i flera hårstudier)

“The low carbon dioxide production of hypothyroidism (e.g., Lee and Levine, 1999), and the respiratory alkalosis of estrogen excess, are often overlooked. An adequate supply of calcium, and sometimes supplementation of salt and baking soda, can increase the tissue content of CO2.” -Ray Peat, PhD

(Kalcium spelar även roll för blodkärl etc. Samt för prolaktin, som i tester på djur har visats påverka när djuren fäller hår på sommaren etc)

Här skriver han om hur mead acid kan fungera som signalsubstans för stamceller. Undra om man kan återfå förmågan att skapa Mead acid. Eller om det är omöjligt att få så låg nivå av pufa i kroppen i vuxen ålder. Eller om man kan supplementera med mead acid eller oleic acid eller palmitic acid…

“When mitochondria are functioning fully, either glucose or saturated fats can safely provide energy. Some glucose or saturated fat can be converted to polyunsaturated fats, that can be used as regulators or signals, for example to activate the formation of stem cells. But those PUFA don’t create disruptive cascades of increasing excitation or inflammation or excessive growth, and, from the evidence of animals that are fed fat free diets, or diets lacking omega -3 and omega -6 fatty acids, they aren’t toxic to mitochondria.”

“The fetus produces saturated fats such as palmitic acid, and the monounsaturated fat, oleic acid, which can be turned into the Mead acid, ETrA (5,8,11-eicosatrienoic acid), and its derivatives, which are antiinflammatory, and some of which act on the “bliss receptor,” or the cannibinoid receptor.

Så med andra ord eftersom det finns flera problem eller orsaker som kan bidra till håravfall, så kanske det inte är så konstigt hur olika personer reagerar olika på olika behandlingar. Laser fungerar för vissa men inte andra (aktiverar cytochrome oxidase). Det finns en del individer online som säger att massage har get dem mer hår (fibros?). Olika tillskott eller preparat tex.

Har även läst på stopaga, om en sak som använde koppar och zink joner i skalpen som gav återväxt hos många. Koppar aktiverar också cytochrome oxidase.

Allt detta stämmer även med det faktum att kvinnor drabbas mindre ofta, vilket är pga kvinnligt hormon progesterone. Alla kvinnor jag ser med tunt hår har tydliga tecken på hypotyreos och lågt progesterone och högt östrogen. Stämmer även med all dagens dogma om östrogen och skit, som är helt bakvänt.

Jag vet även om några personer irl, som fick tillbaka hår av progesterone (och då hade inte minox eller något fungerat tidigare). Dock är det kvinnligt hormon, så det kanske inte är så passade av andra anledningar.