Q: When you say several effects of CO2 shuts off glycolysis, do you mean anaerobic glycolysis or all glycolysis, if all glycolysis how does glucose enter mitochondria without breaking down to pyruvate?
A: Meaning the entry of lactate into the blood stream inappropriately, which would usually be called aerobic glycolysis, though you can't be sure how much oxygen is getting to the cells when CO2 is deficient, since its absence causes many problems in oxygen delivery and use. (Ray Peat, 2012)
Tying together the role of unsaturated fats, carbon dioxide, progesterone, estrogen, prolactin, and thyroid in the genesis of pattern hair loss is the unusual phenomenon of neonatal "male-pattern baldness" (NPB).
Soon after birth, alopecia develops in many babies in the same areas that become bald in adult men, that is, in the frotoparietal regions. This process occurs for weeks or months and happens in both sexes. While hairs are still being lost, new hairs appear on the surface of the scalp and by the end of the first or second year of life, most children have regrown all of the lost hair.
Because NPB occurs soon after birth, in most babies, of both sexes—I'm tempted to believe that the cause is unrelated to "the genes" and "male" androgens. (Check out this video if you're under the impression that those things determine pattern baldness.)
In the context of stress, energy, and aging, however, I think things become a bit clearer.
Protective Carbon Dioxide and Harmful Prolactin
Giving birth can be considered a stressful event, not only for the mother, but for the newborn, too. For example, the womb is a hypoxic environment, and allows the fetus to accumulate a large amount of carbon dioxide in its tissues (i.e., the Bohr effect). Upon exiting the womb, the "respiratory advantage" of a high exposure to carbon dioxide would decrease, possibly interfering with the energy-hungry metabolism of the hair follicles.
If correct, this would offer an explanation for the grossly elevated levels of prolactin often seen in neonates of both sexes (i.e., witch's milk).[3,4] As mentioned previously, prolactin is an adaptive "stress" hormone that inhibits mitochondrial energy metabolism, and suppresses thyroid function. In 2013, Vidali et al. referred to thyroid hormones as "mitochondrial hair medicine". Elevated levels of prolactin are clinically associated with "male-pattern baldness." Additionally, when hair follicles are exposed to high levels of prolactin experimentally the hormone interferes with the growth cycle, terminating it prematurely.
In my own personal research, prolactin levels of men and women with hair issues tend to hover around 10-30 ng/mL.
Carbon dioxide, which is largely produced under the direction of good thyroid function, works in the opposite direction of prolactin. For example, carbon dioxide supports bone growth, prolactin inhibits it; carbon dioxide promotes thyroid hormone, prolactin suppresses it; and carbon dioxide regulates mineral balance, while prolactin retards it.
The Enhanced Regenerative Abilities of Youth
The loss of hair in a "male-pattern baldness" fashion, followed by quick regrowth, may represent the enhanced regenerative abilities of youth. Because the newborn animal is relatively "essential fatty acid" deficient, the "stress" of leaving the womb—and its effect on hair follicles—may be easily overcome by the enhanced respiratory efficiency of the newborn.
"Essential fatty acid" deficiency is protective against endotoxin, estrogen, and the development of diabetes, which are all generally issues for the balding adult.
In the absence of the "essential fats," the body produces its own omega-9 unsaturated fat called mead acid, which is a strong antiinflammatory.
This view of NPB might seem unreasonable given the idea that "male-pattern baldness" is the result of the very slow process "miniaturization". Traditionally, it is believed that pattern baldness occurs over many years with the hair follicles reducing in size and depth in the skin and producing smaller paler hair. However, new evidence suggests that miniaturization is an abrupt, large-step process that also can be reversed in a single hair cycle.
I think this provides further evidence for the extreme sensitivity of the hair follicles to shifts in cellular energy metabolism as first detailed in in 2013's, HAIR LIKE A FOX, which is largely based on the visionary work of Raymond Peat, PhD.
- Hamilton, J.B. Patterned loss of hair in man; types and incidence. Ann N Y Acad Sci. 1951 Mar;53(3):708-28. "In six of these eight specimens, the hair over the frontoparietal and frontal areas, but not over the tonsure, was thinner than elsewhere on the scalp" "The Scalp in the First Two Yearsof Postnatal Life. Soon after birth, a marked alopecia develops in many babies in the same areas that become bald in adult men, that is, in the frontoparietal and frontal areas, and even over the tonsure. This process continues for weeks or months and occurs in both sexes. While hairs are still being lost, new hairs appear on the surface of the scalp and, by the end of the first or second year, most children have a completely hairy scalp of Type I or IA."
- Kenji, A., et al. Human Hair Follicles: Metabolism and Control Mechanisms. J. Soc. Cosmet. Chem., 21, 901-924 Dec. 9, 1970. “As far as energy requirement is concerned, one can assume that the growing hair follicle synthesizing keratin require much more energy than the resting ones. Thus, the pathways to yield ATP, a chemical form of energy, should be accelerated to meet this requirement.”
- Friesen, H. and Hwang, P. Human prolactin. Annu Rev Med. 1973;24:251-70. "In the full term newborn, prolactin levels are grossly elevated compared with adults, and the hormone concentration remains elevated for a longer period in premature infants."
- Coulter, D.M. Prolactin: a hormonal regulator of the neonatal tissue water reservoir. Pediatr Res. 1983 Aug;17(8):665-8. “A number of factors including, the early third trimester rise in fetal serum prolactin levels, their rapid fall during the neonatal period, the ubiquity of prolactin receptors in fetal tissues, the short serum half-life of the hormone, and its possible role in fetal osmoregulation, led us to test the hypothesis that prolactin is a regulator of neonatal tissue water stores. The data presented herein support that hypothesis. They do not, however, exclude a role for other hormones.”
- Spätling, L., et al. Influence of prolactin on metabolism and energy production in perfused corpus luteum bearing bovine ovaries. Arch Gynecol. 1982;231(4):263-7. "Under the influence of PRL anaerobic glucose metabolism was stimulated by 40.5% and oxidative phosphorylation was inhibited. Energy production from aerobic glucose metabolism rose by only 0.25%. Unlike PRL, Human Menopausal Gonadotropin (hMG) and Human Chorionic Gonadotropin (hCG) stimulated aerobic metabolism. This may indicate that PRL is the "older" hormone in phylleogenetic terms."
- Strizhkov, V.V. [Metabolism of thyroid gland cells as affected by prolactin and emotional-physical stress]. Probl Endokrinol (Mosk). 1991 Sep-Oct;37(5):54-8. "A conclusion has been made that one of the most important mechanisms of the adaptive effect of PRL is its ability to suppress thyroid function, thus decreasing the metabolism level, which results in reduction of oxygen consumption and improves body tolerance to stress."
- Vidali, S., et al. Hypothalamic-Pituitary-Thyroid Axis Hormones Stimulate Mitochondrial Function and Biogenesis in Human Hair Follicles. J Invest Dermatol. 2013 Jun 27. “The current data also provide clinically relevant pointers to how HF aging and disease correlated with declining mitochondrial function might be effectively counteracted in the future by endogenous neurohormones produced in the human epithelium, e.g., TRH and TSH. This also applies to THs [thyroid hormones], which have long been known to modulate hair shaft quality and/or pigmentation. Both TRH and T4 are administered routinely in thyroid medicine and are FDA-approved agents with a well-known toxicity profile. Therefore, regulatory hurdles to reposition these hormones for novel ‘mitochondrial hair medicine’ approaches are relatively low.”
- Schmidt J.B., et al.[Hyperprolactinemia and hypophyseal hypothyroidism as cofactors in hirsutism and androgen-induced alopecia in women]. Hautarzt. 1991 Mar;42(3):168-72. “The frequency of subnormal values in SHBG, FSH, testosterone and epitestosterone (but not in free androgen index) was significant in the balding men. A borderline significant trend was recorded with respect to increased levels in 17OH-P and prolactin.”
- Foitzik, K., et al. Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression. Am J Pathol. 2006 Mar;168(3):748-56. “Our data suggest that PRL acts as an autocrine hair growth modulator with catagen-promoting functions and that the hair growth-inhibitory effects of PRL demonstrated here may underlie the as yet ill-understood hair loss in patients with hyper-prolactinemia.”
- Canzanello, V.J., et al. Effect of chronic respiratory acidosis on calcium metabolism in the rat. J Lab Clin Med. 1995 Jul;126(1):81-7.
- Seriwatanachai, D. et al. Prolactin directly enhances bone turnover by raising osteoblast-expressed receptor activator of nuclear factor kappaB ligand/osteoprotegerin ratio. Bone. 2008 Mar;42(3):535-46.
- Savourey, G., et al. Pre-adaptation, adaptation and de-adaptation to high altitude in humans: hormonal and biochemical changes at sea level. Eur J Appl Physiol Occup Physiol. 1998;77(1-2):37-43. “To achieve our objectives, nine subjects received intermittent acclimation at low pressure in a barometric chamber (8 h daily for 5 days, day 1 at 4500 m, day 5 at 8500 m) before an expedition to the Himalayas. Hormonal and biochemical changes were studied using samples of venous blood taken at sea level before and after acclimation, after return from the expedition and 1 and 2 months after descent.“ “After the expedition, hormone responses were characterized by a higher total triidothyronine concentration (+18%, P < 0.05) while other hormones did not vary.“
- Richalet, J.P., et al. Effects of high-altitude hypoxia on the hormonal response to hypothalamic factors. Am J Physiol Regul Integr Comp Physiol. 2010 Dec;299(6):R1685-92. doi: 10.1152/ajpregu.00484.2010. Epub 2010 Oct 6. “Thyroid hormones were elevated at altitude (+16 to +21%), while TSH levels were unchanged, and follicle-stimulating hormone and prolactin decreased, while leutinizing hormone was unchanged.”
- Kenneth McCormick and Moira Shea. Hyperprolactimenia In Congenital Hypothyrodism. Pediatric Research (1984) 18, 171A–171A. "Prolactin levels declined in parallel with TSH levels upon thyroid replacement." "Since prolactin affects mammalian salt and water metabolism, even in neonates (Ped Res 17:665, 1983), enormous elevations of this hormone may explain in part the edema occasionally observed in congenital hypothyroidism."
- Kunkel Ho, Williams Jn Jr. The effects of fat deficiency upon enzyme activity in the rat. J Biol Chem. 1951 Apr;189(2):755-61. "A fat deficiency in the rat causes a marked increase in liver cytochrome oxidase activity... " "Supplementation with 100 mg. of methyl linoleate per rat per day reduced the cytochrome oxidase to the level of that produced by a 5 percent corn oil diet."
- Li, E.J., et al. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability. Circ Shock. 1990 Jun;31(2):159-70.
- Obinata, K., et al. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability. Circ Shock. 1990 Jun;31(2):159-70. “Hepatic bile salt sulphotransferase (BSS) activity and the contents of unconjugated oestradiol-17 beta (E2) and conjugated oestrone (cE1) in liver tissue was significantly lower in young essential fatty acid (EFA) deficient female rats than in female control rats.” “The decrease in hepatic BSS activity in female rats caused by EFA deficiency may be mediated via a decreased estrogenic action on the liver.”
- Wright, J.R., et al. Essential fatty acid deficiency prevents multiple lowdose streptozotocininduced diabetes in CD1 mice. Proc Natl Acad Sci U S A. 1988 Aug;85(16):613741. “Histologic examination of the pancreata of control mice or repleted mice showed marked insulitis and beta cell destruction; in contrast, the pancreata of essential fatty aciddeficient mice showed preservation of beta cells and only focal mild periinsulitis. Essential fatty acid deficiency thus prevents the insulitis and resultant diabetes in lowdose streptozotocintreated CD1 mice, suggesting a central role for macrophages and lipid mediators in this autoimmunity model.”
- Lefkowith, J.B., et al. Essential fatty acid deficiency: a new look at an old problem. Prostaglandins Leukot Med. 1986 Aug;23(23):1237. “EFA deficiency has been shown to exert an antiinflammatory effect.”
- Whiting, D.A. Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss. J Am Acad Dermatol. 2001 Sep;45(3 Suppl):S81-6. "In androgenetic alopecia, or pattern hair loss, follicles undergo miniaturization, shrinking from terminal to vellus-like hairs. Traditionally, this process is thought to progress gradually over a number of follicular cycles. However, it is unlikely that miniaturization can be explained only by a series of progressively shorter anagen cycles. Simple calculations show that this process would take too long for significant miniaturization to occur secondary to shorter anagen cycles alone, especially in view of the latent lag period seen in pattern hair loss that occurs between the loss of a telogen hair and the appearance of an anagen hair. Evidence is presented to support a new concept that miniaturization is an abrupt, large-step process that also can be reversed in 1 hair cycle, as has been shown clinically, with confirmatory histologic evidence, in patients with pattern hair loss responding to finasteride treatment. It is hypothesized that the miniaturization seen with pattern hair loss may be the direct result of reduction in the cell number and, hence, size of the dermal papilla."