The Centrality of The Liver in Pattern Baldness: Estrogen, Aspirin, and IGF-1


After consuming only meat and water every day for two years, there came a point where I felt like I was constantly on edge. This feeling was not only evident to me but anyone who was around me on a regular basis, especially my former band mates. For instance, the singer of Takota, who I was closest to, told me that 99% of the time he was around he felt like he was walking on eggshells. This eggshell walking was most evident on tour, where I was a complete raging lunatic — regularly throwing temper tantrums in protest of the guitar player's actions who I had a love/hate relationship with. In retrospect, this orientation is almost expected given my no-carb diet, which induced a state of near constant low blood sugar.

The effects of low blood sugar on one's mood is best described by pioneering stress physiologist, Hans Selye, in his 1976 book, The Story of Adaptation Syndrome.[1] During his time as a medical student, Selye's professor injected insulin in the students one by one so they would better recognize the signs of hypoglycemia. The demonstration was running smoothly until the professor injected a classmate with a learning disability, who was universally adored. Upon receiving the injection, the sweet student transformed into a "monster" and began wrestling with the other students. While being forcefully restrained, the professor shoved candy in the student's mouth causing him to snap out of the insulin-induced tailspin. This concluded the experiment.

Image: “Some of the clinical signs and symptoms of [excess estrogen] are, in the male, gynecomastia, softening of the testes, loss of axillary hair, impotence, and decreased libido, and, in the female, menstrual disturbances, breast changes and symptoms, and acne. Infertility may occur in both sexes.” —The Liver and Estrogen Metabolism (1951)

Image: Some of the clinical signs and symptoms of [excess estrogen] are, in the male, gynecomastia, softening of the testes, loss of axillary hair, impotence, and decreased libido, and, in the female, menstrual disturbances, breast changes and symptoms, and acne. Infertility may occur in both sexes.” —The Liver and Estrogen Metabolism (1951)

Similar to the student, low thyroid individuals are especially susceptible to low blood sugar, or hypoglycemia. In Dr. Broda Barnes 1978 classic, Hope for Hypoglycemia: It’s Not Your Mind It’s Your Liver, he noted that in patients with poor thyroid activity the liver was unable to store sufficient amounts of sugar in the form of glycogen.[2] During periods of fasting, instead of balancing the blood sugar and restraining the stress response, a low thyroid person essentially ran out of sugar, requiring compensation from the stress substances: adrenaline and glucagon (in the short-term) and cortisol (in the long-term).

An impaired liver and an excess of adrenaline and cortisol not only affect behavior but can cause systemic effects in the entire organism. For example, the increased concentration of these substances, and the subsequent release of fatty acids to use as fuel, appears to be part of a much bigger attempt to slow the entire system down  by reducing the "efficient" production of energy (i.e., glucose to carbon dioxide) in order to go longer on less. While this adaptive response is useful for survival, it has a negative impact on the energy intensive process of hair growth. A major force acting against the growth of hair, I think, is the increased synthesis of estrogen.

I: Estrogen and The Liver

The liver is majorly responsible for detoxifying estrogen in the body.[3] When the liver becomes impaired, for example in hypothyroidism or cirrhosis, both estrogen and prolactin tend to increase.[4,5] In excess, estrogen is "toxic" to the liver[6], and in a vicious cycle, estrogen impairs liver function.[7] While the current climate of citizen hair loss research appears to be extremely confused about the role of estrogen in pattern baldness, I think historically it has always been viewed as a growth inhibitor.

As early as 1945, it was known that estrogen had a negative effect on hair growth.[8] Even Dr. James B. Hamilton, the physician that coined the concept of "male-pattern baldness," noted the "anti-hair" properties of estrogen.[9] In Montagna's 1958 epic, The Biology of Hair Growth, they stated that “it is agreed that estrogenic hormones inhibit hair growth."[10] Estrogenic contraceptive drugs can induce male-pattern baldness.[11,12] And more recently, in 1994, Schmidt et al. found increased levels of estrogen in males with pattern hair loss.[13] Hormone-like messengers called prostaglandins, which Garza et al. found to inhibit hair growth in 2012,[14] are increased by estrogen.[15]

Cyproterone acetate has historically been "useful" in treating pattern baldness in both men and women. While often labeled as an antiandrogen, cyproterone acetate "has a strong progesterone potency,"[16] and reduces estrogen levels down to "castrate levels."[17] When topical progesterone and estrogen were compared in 1975 for treating baldness, the authors felt that progesterone was more effective than estrogen, but that thyroid hormone had the most scientific rationale.[18] 

During the period of therapy with diethylstillbestrol [synthetic estrogen] there was decided loss of scalp hair and other hair, and the patient refused to continue longer to take that estrogen.
— Effect of endocrine substances on the adult human scalp (1945)

Estrogen increases the pituitary hormone prolactin,[19,20] and prolactin can "mimic" the effects of androgens.[21] Prolactin inhibits hair growth,[22] and is associated with pattern baldness.[23] Both hormones suppress thyroid function,[24,25] and low thyroid function is associated with so-called male-pattern baldness.[26] Thyroid hormone is needed to produce the antiestrogen, progesterone, and active thyroid hormone is produced largely by the liver. A decrease in the rate of metabolism, and the subsequent decrease in liver functionality increases the synthesis of estrogen in a few ways. 

• Lactic Acid

In a situation where sugar is purposefully being restricted,[27] or is being used inefficiently, such as diabetes,[28,29] levels of lactic acid tend to increase. Sometimes it's said that lactic acid is a useful fuel, however, in a process called the "Cori cycle" lactic acid is sent to the liver, where it requires glycogen to be converted back into glucose.[30] It should be pointed out that this process is essentially a setback, as stealing the liver's important reserve of sugar is constructive for survival, but not necessarily the energy intensive process of hair growth.[31,32] It is also said that diabetics "can't use sugar" but the increased production of lactic acid in the blood of diabetics suggests that sugar does get into the cell, but it is oxidized inefficiently to lactic acid instead of carbon dioxide, suggesting the central role of metabolic stress in diabetes.[33] 

I think the increased production of lactic acid is meaningful, as an "efficient" metabolism restrains the production of lactic acid.[34] The increased concentration of lactic acid, and a decrease in carbon dioxide can increase estrogen synthesis,[35] and the reliance on substances that mobilize fatty acids as an alternative "back up" fuel. An increased concentration of fat in the blood is metabolically stressful.[36,37] If the diet has contained a disproportionate amount of polyunsaturated to saturated fats in the diet, the stress tends to self-accelerate,[38] increasing the synthesis of estrogen.[39,40]

• The Prostaglandins

Estrogen can increase the synthesis of hormone-like messengers called prostaglandins.[41] There are opposing views on the nature of prostaglandins, but their appearance seems to be exclusively negative in pattern baldness. For example, prostaglandin D2 inhibits hair growth,[42] and prostaglandin E2 (PGE2) can increase the activity of aromatase.[43] PGE2 and the COX-2 pathway are targets for cancer therapy.[44] Prostaglandins interfere with the "efficient" use of glucose,[45] the main source of fuel for hair follicles.[46] Additionally, prostaglandins can intensify the stress reaction by activating the pituitary.[47] W.D. Denckla believed that the function of the pituitary was to decrease tissue's responsiveness to thyroid hormone.[48]

• Sex Hormone Binding Globulin (SHBG) & Albumin

An impaired liver produces less steroid binding protein, or sex hormone binding globulin (SHBG). SHBG is decreased in pattern baldness,[49] which explains higher ratio between “free” testosterone and testosterone. A lack of SHBG also increases estrogen, as SHBG binds and neutralizes estrogen in the blood. In addition to less SHBG, an impaired liver produces inadequate albumin. In 1976 Jordan et al. found that "serum albumin showed significant correlation with the protein content of the growing hair root bulbs", and that "there was significant correlation between the percentage of growing hairs, their bulb diameters, and protein content, which in turn, correlated with the protein intake of the subject."[50]

II: Estrogen and IGF-1

Another feature of an impaired liver is a decreased level of insulin-like growth factor 1, or IGF-1. Many things are said about the nature of IGF-1, however, in the context of baldness, it appears to be involved in healthy hair growth.[51] In fact, one paper suggested that IGF-1 was a “promising drug candidate for baldness therapy.”[52] IGF-1 should not be confused with growth hormone; growth hormone tends to rise and fall with the adaptive stress substances, such as prolactin,[53] while IGF-1 decreases with age and during malnutrition.[54,55] 

When people talk about IGF-1 as "plug and play cancer fuel" I think the statement is extremely misleading. First, IGF-1 decreases with age and is highest during youth, when cancer is least likely to occur. Supplemental estrogen significantly decreases the liver's production of IGF-1.[56] Speaking of cancer... Estrogens are among the best known of the growth stimulants,[57] tend to increase with age in both sexes,[58,59] and promote Warburg's cancer metabolism (i.e., aerobic glycolysis).[60] Thyroid works in the opposite direction (thanks Haidut).[61]

III: Aspirin, Glycine, and Fructose

In addition to keeping thyroid function up, minimizing the polyunsaturated fats, and consuming an easy-to-digest diet, I think there are some additional therapies to support liver function:

Aspirin: In his article, Aspirin, brain, and cancer, Dr. Peat notes that very often people ignore his suggestion to consume aspirin based what seems to be a very strong cultural bias. I had a similar orientation when I first read Dr. Peat's article, but since experimenting with it, I've found aspirin to be a cheap and effective antiinflammatory. Rather than damaging the liver like other over the counter antiinflammatories, aspirin appears to play a protective role. For example, high doses of acetaminophen, the main ingredient in Tylenol, has been shown to induce severe liver damage. However in an experiment when mice were administered aspirin concurrently with the Tylenol they experienced "invulnerability to liver damage.”[62] Aspirin is useful for inhibiting the Randle cycle in fat-induced insulin resistance,[63] "may become a new drug for osteoporosis,"[64] and can support the metabolism similar to thyroid hormone.[65] Aspirin can deplete vitamin K,[66] so it might be a good idea to supplement it at the same time. Also, dissolving aspirin in warm water, and consuming it with a meal, may help overcome any possibility of intestinal irritation.

Glycine (Gelatin): In stress, the enzyme tryptophan hydroxylase tends to increase, synthesizing serotonin from the amino acid tryptophan. As I've mentioned, excess serotonin is probably a fundamental factor in the genesis of pattern baldness, and limiting its production is probably worthwhile. In contrast to muscle meats, protein sources that provide gelatin (e.g., oxtail, shanks, broth) are deficient in tryptophan, and contain large amounts of the antiinflammatory amino acid, glycine. Glycine protects against liver damage from alcohol,[67] bacterial endotoxin,[68] and may be a chemoprotective agent.[69] In 2012, Dr. Zeev Pam noted that from his many years of experience in his clinical practice that oral gelatin was a safe and effective treatment for pattern hair loss.[70] Great Lakes makes some high-quality gelatin supplements, however, they're becoming increasingly expensive. A few tablespoons mixed in with coffee or juice is probably enough to obtain the benefits of glycine. Oxtail, chicharrones, and lamb shanks are other sources of gelatin.

Fructose — Carbohydrates are disposed of three different ways: they can be combined with oxygen to produce energy, stored as glycogen in the muscles and liver, or converted to fatty acids via de novo lipogenesis (DNL) and stored as triglyceride. A common argument against fructose is that it is shunted directly to the liver where it is converted to fat, setting the stage for fatty liver disease (NAFLD), diabetes and obesity. While it is true that the liver rapidly uses fructose, it does so primarily to refill hepatic glycogen. In one study, an infusion of fructose resulted in about 360 percent more glycogen than a glucose infusion.[71] And the liver's capacity for glycogen is very large. One study suggested that "de novo lipogenesis [DNL] is not an important pathway in humans" and that chronic overfeeding on carbohydrates increased glycogen stores of about 500 grams before DNL became significant.[72] The liver uses glycogen locally for its various tasks, so keeping it "energized" is a simple and effective way to support its function.   

IV: Synthesis

Low thyroid, impaired liver function, the exchange of lactic acid for carbon dioxide, the inhibition of glucose oxidation, the increased reliance on fat as fuel, a shift towards the adaptive "stress" substances, and a chronic generalized state of inflammation are probably all central events in the genesis of The Baldness Field. 

Image: Top: un-stimulated mast cell with its condensed quiescent granules. Bottom: stimulated mast cell with many activated decondensed granules.

Image: Top: un-stimulated mast cell with its condensed quiescent granules. Bottom: stimulated mast cell with many activated decondensed granules.

The baldness field, or the classic horseshoe shape of pattern hair loss, is characterized by an increased concentration of mast cells.[73] Mast cells are "early responders" to systemic hypoxia, initiating the inflammatory cascade.[74,75]

The concentration of mast cells in the prostate is a novel prognostic marker for prostate cancer.[76] Baldness is strongly associated with developing prostate cancer, and perhaps the mechanisms are similar.[77] Prolactin appears to be associated with both problems,[78] and like all of the stress hormones, is involved in the recruitment and degranulation of mast cells.[79] 

By generating carbon dioxide, active thyroid hormone is responsible for sufficiently oxygenating tissues (i.e., the Bohr effect). Carbon dioxide restrains mast cells from degranulation,[80] inhibiting the release of prostaglandin D2 and other growth inhibitors.

I think it's time to begin viewing baldness as, to steal a phrase from Ray, a "regulatory weakness" within the organism. I suspect that reversing the inflammatory processes that have developed — over a lifetime — is difficult without good nutrition and a few useful supplements. Moreover, self-metrics (e.g., the resting pulse and temperature) and for some, lab work, should regularly be employed to guide the entire ship in the right direction.


  1. Selye, H. The Story of Adaptation Syndrome. 1952. [Book]
  2. Barnes, B. Hope For Hypoglyemia: It’s Not Your Mind, It’s Your Liver. 1978. [Book]
  3. Biskind, M.S. Nutritional Aspects of Endocrine Disease. Am J Clin Pathol. 1946 Dec;16(12):737-45. “The majority of the patients with syndromes related to excess estrogen studies by M.S., G.R. and L.H. Baskind had a low basal metabolic rate. This was especially true of the patients with signs of severe or moderately severe nutritional deficiency. Administration of thyroid to these patients, in the absence of a vitamin B supplement, usually caused exacerbation of the signs and symptoms of deficiency without significant change in the metabolic rate. The low metabolic rate in these patients maybe the expression of a safety mechanism; the rise in body estrogen resulting from failure of inactivation in the liver depresses the pituitary with diminution in secretion of the thyrotropic principle.” “It seems likely that dietary estrogen, which normally is destroyed in the liver, would largely or entirely escape inactivation in vitamin B complex deficiency and, added to endogenous estrogen, already in excess, would exert a further deleterious effect. That failure of inactivation of dietary estrogen occurs in cirrhosis of the liver…” “Numerous studies already cited have establish that cirrhosis of the liver can be produced by nutritional deficiency or nutritional imbalance and that B vitamins (especially choline) and the protein content of the diet play a major role in this phenomenon."
  4. Long, R.S., and Simmons, E.E. The liver and estrogen metabolism; report of cases. AMA Arch Intern Med. 1951 Dec;88(6):762-9.
  5. Payer, J., et al. Prolactin levels in patients with cirrhosis increase with severity of liver disease. Endocrine Abstracts 2008 16 P436. “Prolactin levels increase significantly with severity of liver disease particularly in patients with ascites and hepatic encefalopathy. High prolactin level could therefore be considered as a negative prognostic marker of liver cirrhosis.”
  6. Yang, J.M., et al. The metabolic effects of estriol in female rat liver. J Korean Med Sci. 1999 Jun;14(3):277-85. “Basal oxygen consumption of perfused liver increased significantly in estriol or ethanol-treated rats.” “In isolated Kupffer cells from estriol-treated rats, intracellular calcium was more significantly increased after addition of lipopolysaccharide (LPS) than in controls. These findings suggest that the metabolic effects of estriol (two mg per 100 mg body wt) can be summarized to be highly toxic in rat liver, and these findings suggest that oral administration of estrogens may induce hepatic dysfunctions and play a role in the development of liver disease.”
  7. Tarantino, G., et al. Oral contraceptive and hepatic effects. European Review for Medical and Pharmacological Sciences. 1990, 12(3):165-168. “ “The general use of synthetic estrogens like DC pointed out that near many skilled collateral effects, some others that are showing with a decrease of bile excretion (cholestasis), reversible with their administration interruption…”
  8. Rony, H. and Zakon, S. Effect of endocrine substances on the adult human scalp. Arch Derm Syphilol. 1945;52(5):323-327. ”During the period of therapy with diethylstilbestrol [synthetic estrogen] there was decided loss of scalp hair and other hair, and the patient refused to continue longer to take that estrogen.”
  9. Hamilton, J.B. Male hormone stimulation is prerequisite and an incitant in common baldness. Am J Anat 71:451-480 1942. “Decrease in androgenic secretion can be attained also upon administration of estrogens, either as a result of inhibiting gonadotropic secretions or possible by direct antagonism between androgens and estrogens, but estrogens in themselves have been demonstrated to prevent the proper growth of hair.”
  10. Montagna, W. The Biology of Hair Growth. 1958. “It is agreed that estrogenic hormones inhibit hair growth.”
  11. Cormia, F.E. Alopecia From Oral Contraceptives. JAMA. 1967;201(8):635-637. “Diffuse alopecia of the scalp developed in five patients during or following administration of oral contraceptive drugs. That occurring during administration resembles alopecia of the male-pattern type, while that developing after discontinuance is comparable to telogen effluvium. Alopecia from oral contraceptive may be associated with other types of diffuse scalp hair loss and it may be a frequent cause of hair loss in women.”
  12. Greenwald, A.E. [Oral contraceptives and alopecia]. Dermatol Iber Lat Am. 1970;12:29-36. “Of five women who developed fiffuse slopecia while taking oral contraceptives, three had male pattern baldness while they were taking the treatmen; two began to lose their hair after having stopped taking the treatment, adn these resembled postpartum bladness.” 
  13. Schmidt JB. Hormonal basis of male and female androgenic alopecia: clinical relevance. Skin Pharmacol. 1994;7(1-2):61-6. “Our findings showed a significant elevation of cortisol in both male and female AH patients compared to controls, pointing to the suprarenes as a contributing factor in AH. This is confirmed by the observation of exacerbated AH in periods of increased stress.” “The mainly peripheral activity of this hormone and elevated E2 levels in males stress the importance of androgen metabolism especially at the peripheral level.” “Another significant finding was elevated PRL after TRH stimulation. Thus, the androgen-stimulating effect of PRL may also play a role in female AH. Our findings show multilayered hormonal influences in AH.”
  14. Garza, L.A., et al. Prostaglandin d2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med. 2012 Mar 21;4(126):126ra34. “Given the androgens are aromatized into estrogens, these results may be relevant to hair growth and alopecia in both men and women. Thus, these or similar pathways might be conserved in the skin and suggest that sex hormone regulation of Ptgds may contribute to the pathogenesis of AGA.” “…demonstrates elevated levels of PGD2 in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD2 as an inhibitor of hair growth in AGA and suggest the PGD2-GPR44 pathway as a potential target for treatment.”
  15. Toda, K., et al. 17β-Estradiol is critical for the preovulatory induction of prostaglandin E(2) synthesis in mice. Mol Cell Endocrinol. 2012 Oct 15;362(1-2):176-82. “Furthermore, significant elevation in the PGE(2) contents was detected in the preovulatory ovaries of ArKO mice after stimulation with E2 plus ovulatory doses of gonadotropins. Thus, these analyses demonstrate a requirement of E2 for the preovulatory enhancement of PGE(2) synthesis, leading to future success in ovulation.”
  16. Neuman, F., and Graf, K.J. Discovery, development, mode of action and clinical use of cyproterone acetate. “CA has been useful in treating androgen-dependent tumors and ‘androgenic’ diseases such as idiopathic precocious puberty, hirsutism, and male-pattern baldness in adult females, all signs of virilization in females, hypersexuality in adult males, acne and seborrhea, baldness in adult males, and benign prostatic hypertrophy.” “Because of its strong progesterone potency…” “Gynecomastia sometimes develops temporarily in males treated with CA. Serious side effects of CA treatment have not been observed.”
  17. Geller, J., et al. Effect of cyproterone acetate on clincal, endocrine and pathological features of benign prostatic hypertrophy. Journal of Steroid Biochemistry, 1975. Vol. 6, pp. 837-843. “Clinical effects of CPA in patients with BPH. In five patients treated with CPA, 250 mg daily by mouth for two-to-four months, all improved clinically (Table 2) by both objective (residual urine and ability to void) and subjective criteria. The resected prostate was surprisingly small compared to the expected values estimated prior to drug treatment.” “The decrease in estrogen to the castration levels demonstrated in two patients during CPA therapy may reflect either a decrease in estrogen secondary to a decrease in testosterone which serves as a precursor for the estrogen, or it may reflect the direct inhibition of estrogen synthesis by Leydig cells. Since estrogen may stimulate squamous metaplasia and fibromuscular growth in the middle and lateral lobes of prostate, the usual anatomic sites of BPH, decreased estrogen production rates with CPA may have relevance to the clinical effects of the drug in BPH.”
  18. Theodore, A., et al. Medical treatment of male pattern alopecia (androgenic alopecia). Head Neck Surg. 1985 Mar-Apr;7(4):336-9. “A therapeutic trial of topical progesterone at a 2%-5% concentration appears to be reasonable when the physician and patient appreciate the limitations of this approach.” “Attempts to interfere with androgen production or utilization have in the past involved the administration of estrogens systemically, topically, or through injections into the scalp. However, this again has not produced consistent positive clinical results. Some physicians formerly injected estrogen into the scalp. However, the lack of consistent clinical results and the potential for distant estrogenic effects if large quantities are used have caused many physicians to no longer use this form of therapy. It certainly could have a significant placebo effect. Physicians using injections into the scalp generally now inject a dilute suspension of aqueous progesterone, 3.O- 5.0 mg/ml, with or without triamcinolone acetonide, 1.0 mg/ml. This has not been associated with adverse distant side effects.” “Experimentally, thyroid hormone can produce increased amounts of testosterone binding protein and can increase the rate of hair growth in animals, which explains the use of thyroid hormone in AGA. However, significant clinical benefit has not been shown with this technique although it does enjoy a scientific rationale.” “AGA is probably a series of diseases with a common end pathway.”
  19. Yen, S.S., et al. Augmentation of prolactin secretion by estrogen in hypogonadal women. J Clin Invest. 1974 Feb; 53(2): 652–655. “The effect of estrogen on prolactin (PRL) release and gonadotropin suppression was assessed in six experiments performed on four hypogonadal women. Ethinyl estradiol at a dose of 1 microgram/kg per day induced a significant elevation of serum PRL levels within the 1st wk of treatment. There was a further rise until a plateau was reached in about 3-4 wk to levels of more than 3 times the initial concentration. This was accompanied by a pattern of increased episodic fluctuation. The corresponding serum luteinizing hormone and follicle-stimulating hormone fell progressively during the study period. These data indicate that a positive feedback relationship between estrogen and PRL release exists in humans.”
  20. Wiedemann, E., et al. Acute and chronic estrogen effects upon serum somatomedin activity, growth hormone, and prolactin in man. J Clin Endocrinol Metab. 1976 May;42(5):942-52. “Chronic E administration (ethinyl estradiol 0.5 mg/day for 7 to 70 days) reduced serum SM activity by 40 to 62% in each of 4 subjects (P less than 0.02 to less than 0.001). In 3 of the subjects, basal GH levels increased by 75 to 300% (P less than 0.05 to less than 0.001) and basal PRL levels increased by 90 to 200% (P less than 0.01 to less than 0.001).” “These results demonstrate that in males with normal pituitary function, E reduces serum SM activity, enhances basal GH and PRL secretion, and, upon iv injection, stimulates acute GH release.”
  21. Orfanos, C.E., and Hertel, H. [Disorder of hair growth in hyperprolactinemia]. Z Hautkr.1988 Jan 18;63(1):23-6. “These observations indicate that cutaneous symptoms such as seborrhea, acne, hypertrichosis/hirsutism, alopecia(= SAHA syndrome) may evidently occur in hyperprolactinemia, representing or mimicking androgen-induced skin symptoms. In such cases, therefore, evaluation of prolactin levels together with androgen blood levels and thyroid gland function tests should be performed to exclude underlying endocrinopathy.”
  22. Foitzik, K., et al. Prolactin and its receptor are expressed in murine hair follicle epithelium, show hair cycle-dependent expression, and induce catagen. Am J Pathol. 2003 May;162(5):1611-21. “In addition we show that PRL exerts functional effects on anagen hair follicles in murine skin organ culture by down-regulation of proliferation in follicular keratinocytes.””The regressing (catagen) follicle showed a strong expression of PRL in the proximal ORS.” “Addition of PRL (400 ng/ml) to anagen hair follicles in murine skin organ culture for 72 hours induced premature catagen development in vitro along with a decline in the number of proliferating hair bulb keratinocytes. These data support the intriguing concept that PRL is generated locally in the hair follicle epithelium and acts directly in an autocrine or paracrine manner to modulate the hair cycle.”
  23. 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. “PRL has also been implicated in the pathogenesis of androgenetic alopecia by modulation of androgens, and hyperprolactemia is associated with an androgenetic alopecia-type hair loss pattern, along with hirsutism (in females).”
  24. Vandorpe, G. and Kuhn, E.R. Estradiol-17P Silastic Implants in Female Rana ridibunda Depress Thyroid Hormone Concentrations in Plasma and the in Vitro 5’-Monodeiodination Activity of Kidney Homogenates. General and Comparitive Endocrinology 76, 341-345 (1989). “After E, treatment, there is a twofold decrease in plasma T4, and the 5’-D activity is two times lower. These two factors could contribute to the fivefold decrease of the plasma T3, concentration.”
  25. Strishkov, 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…”
  26. Schmidt, J.B., et al. [Hypothyroidism and hyperprolactinemia as a possible cause of androgenetic alopecia in the female]. Z Hautkr. 1989 Jan 15;64(1):9-12. “31 female patients suffering from androgentic alopecia were examined by means of the TRH test with regard to hypothyroidism and hyperprolactinemia. Before, as well as 20 and 40 minutes after, application of thyroxine releasing hormone (TRH), the serum concentrations of the hypohyseal thyroxine stimulating hormone (TSH) and prolactin (PRL) were measured by radioimmunoassay (RIA). In 7 of the patients (23%), we found increased TSH levels after stimulation with TRH—indicative of hypothyroidism. In 9 of the patients (29%), we observed increased PRL levels after TRH stimulation, indicating prolactinemia. TSH and PRL can interact with androgen metabolism at various levels. Thyroxine may influence the unbound, metabolically active testosterone via the sex hormone binding globulin (SHBG). Prolactin, which is stimulated by TRH, promotes the suprarenal cortisol and androgen production.In 48% of the patients, we found either hypothyroidism or hyperprolactinemia. This suggests that both conditions may contribute to the clinical picture of female androgenetic alopecia, as they interfere with the androgen metabolism.”
  27. Pan, J.W., et al. Human brain beta-hydroxybutyrate and lactate increase in fasting-induced ketosis. J Cereb Blood Flow Metab. 2000 Oct;20(10):1502-7.
  28. Crawford, S.O., et al. Association of blood lactate with type 2 diabetes: the Atherosclerosis Risk in Communities Carotid MRI Study. Int J Epidemiol. 2010 Dec;39(6):1647-55. doi: 10.1093/ije/dyq126. Epub 2010 Aug 25. “Plasma lactate was strongly associated with type 2 diabetes in older adults. Plasma lactate deserves greater attention in studies of oxidative capacity and diabetes risk.”
  29. Scale, T., and Harvey, J.N. Diabetes, metformin and lactic acidosis. Clin Endocrinol (Oxf). 2011 Feb;74(2):191-6. “Metformin has long been thought to cause lactic acidosis (LA) but evidence from various sources has led researchers to question a direct causative relationship. We assessed the relationship of metformin prescription and other factors to the incidence of LA.” “The incidence of LA was greater in diabetes than in the nondiabetic population but with no further increase in patients taking metformin. Lactate levels were no greater in patients on metformin than in patients with type 2 diabetes not on metformin…” “Diabetes rather than metformin therapy is the major risk factor for the development of LA. Lactic acidosis occurs in association with acute illness particularly in diabetes. Current guidance for the prevention of lactic acidosis may overemphasize the role of metformin.”
  30. Wolfe, R.R., et al. Energy metabolism in trauma and sepsis: the role of fat. Prog Clin Biol Res. 1983;111:89-109. “Rather than being completely oxidized, pyruvate is reduced to lactate and released into the plasma at an accelerated rate. The lactate then contributes to the production of glucose in the liver, completing a cyclical process called the Cori Cycle”
  31. Kenji, A., et al. Human Hair Follicles: Metabolism and Control Mechanisms.  J. Soc. Cosmet. Chem., 21, 901-924 Dec. 9, 1970. “In 1958, Bullough and Laurence reported that mitosis in the hair bulb requires adequate supplies of oxygen and energy sources, such as glucose, fructose, and pyruvate.” “It was found that all of these inhibitors [e.g., cyanide, etc.] decreased CO2 production, and indication that the Krebs cycle is operative in the hair follicles…” “The activity of the Krebs cycle increases about 35% during the growth stage of the hair follicle…” “Thus, in the growing follicles, glucose assimilation produces not only sufficient, energy for the follicles function but also essential substances for the follicle to metabolism fatty acid, nucleic acid, and steroid hormones.”
  32. Williams, R. et al. Metabolism of freshly isolated human hair follicles capable of hair elongation: a glutaminolytic, aerobic glycolytic tissue. J Invest Dermatol. 1993 Jun;100(6):834-40. “We have shown that only 10% of the total glucose utilized was oxidized to CO2 and 40% of this was oxidized via the pentose phosphate shunt. Although fatty acids and ketone bodies were oxidized by the hair follicle, they are poor energetic substitutes for glucose. Nor will fatty acids or ketone bodies sustain hair growth in vitro.” “Sixty-four percent of the glutamine taken up was calculated to be metabolized to lactate, showing that the hair follicle engages in both glycolysis and glutaminolysis.”
  33. Chiodini, I., et al. Cortisol secretion in patients with type 2 diabetes: relationship with chronic complications. Diabetes Care. 2007 Jan;30(1):83-8. “In type 2 diabetic subjects, hypothalamic-pituitary-adrenal activity is enhanced in patients with diabetes complications and the degree of cortisol secretion is related to the presence and number of diabetes complications.”
  34. Warburg, O., et al. Metabolism of Tumors in the Body. J Gen Physiol. 1927 March 7; 8(6): 519–530.
  35. Bushinsky, D.A., et al. Metabolic, but not respiratory, acidosis increases bone PGE(2) levels and calcium release. Am J Physiol Renal Physiol. 2001 Dec;281(6):F1058-66. “In mammals, metabolic[Lactic Acid], but not respiratory [CO2], acidosis increases urine calcium excretion without altering intestinal calcium absorption, indicating that the additional urinary calcium is derived from bone.” “Metabolic acidosis increases bone PGE(2) production, which is correlated with J(Ca), and inhibition of PGE(2) production inhibits this acid-induced J(Ca).” “Thus metabolic, but not respiratory, acidosis induces the release of bone PGE(2), which mediates J(Ca) from bone.”
  36. Wolfe, R.R., et al. Energy metabolism in trauma and sepsis: the role of fat. Prog Clin Biol Res. 1983;111:89-109. “The tissues are attuned to the oxidation of fat, and as a consequence most of the energy production is derived from fat oxidation. The increased fatty acids exert an inhibitory effect on the complete oxidation of glucose, so although glucose may be taken up at an accelerated rate, the relative contribution of glucose oxidation to total energy production may fall.”
  37. Large, V., and Arner P. Regulation of lipolysis in humans. Pathophysiological modulation in obesity, diabetes, and hyperlipidaemia. Diabetes Metab. 1998 Nov;24(5):409-18. “In man, the major hormones are insulin (inhibition of lipolysis) and catecholamines (stimulation of lipolysis). Physiological factors such as dieting, physical exercise and ageing also regulate lipolysis. The lipolytic process is modified in pathological conditions, e.g. obesity (both upper and lower obesity), diabetes (non- and insulin-dependent diabetes mellitus), and dyslipidaemia (in particular, familial combined hyperlipidaemia).”
  38. Katoh, K., et al. Saturated fatty acids suppress adrenocorticotropic hormone (ACTH) release from rat anterior pituitary cells in vitro. Comp Biochem Physiol A Mol Integr Physiol. 2004 Feb;137(2):357-64. Addition of saturated fatty acids (butyrate, caprylate, laurate, palmitate and stearate) in a medium at 1 mmol/l, despite effects on the basal release, significantly reduced the ACTH release induced by CRH (1 nmol/l) stimulation. Caprylate suppressed ACTH release in a concentration-dependent manner. However, unsaturated C18 and C20 fatty acids (oleate, linolate, linolenate and arachidonate) at 1 mmol/l significantly increased the basal release, but none of them suppressed CRH (1 nmol/l)-induced ACTH release. In the presence of caprylate (1 mmol/l), CRH (1 nmol/l)-stimulated increase in cellular calcium ion concentration was diminished. From these results we conclude that saturated fatty acids have a suppressing effect on CRH-induced ACTH increase in primary cultured rat anterior pituitary cells.
  39. Benassayag, C., et al. Potentiation of estradiol binding to human tissue proteins by unsaturated nonesterified fatty acids. Endocrinology. 1986 Jan;118(1):1-7. “Nonesterified fatty acids (NEFAs) have been recently shown in the rat to be involved in steroid hormone expression, having effects on plasma transport and intracellular activity.””Unsaturated NEFAs induced a 2- to 10-fold increase (P less than 0.001) in E2 binding to cytosol from normal, fibromatous, and neoplastic uteri, while saturated NEFAs had a slight inhibitory effect (P less than 0.05).”
  40. Reed, M.J., et al. Free fatty acids: a possible regulator of the available oestradiol fractions in plasma. J Steroid Biochem. 1986 Feb;24(2):657-9. “Consumption of dietary fats has been linked to the high incidence of breast cancer found in Western women. In vitro studies we have carried out show that unsaturated free fatty acids can increase the biologically available oestradiol fractions in plasma. It is possible therefore that the increased risk for breast cancer associated with a diet high in fats may be related to an elevation in the biologically available oestradiol fractions in plasma.”
  41. Thomas, W., et al. Estrogen induces phospholipase A2 activation through ERK1/2 to mobilize intracellular calcium in MCF-7 cells. Steroids. 2006 Mar;71(3):256-65. Epub 2005 Dec 22. “The principal secreted estrogen, 17beta-estradiol rapidly activates signaling cascades that regulate important physiological processes including ion transport across membranes, cytosolic pH and cell proliferation. “ “Here, we demonstrate that a physiological concentration of 17beta-estradiol caused a rapid, synchronous and transient increase in intracellular calcium concentration in a confluent monolayer of MCF-7 cells 2-3 min after treatment. “ “Here we show, for the first time, that PLA(2) and the eicosanoid biosynthetic pathway are involved in the 17beta-estradiol induced rapid calcium responses of breast cancer cells.”
  42. Garza, L.A., et al. Prostaglandin d2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med. 2012 Mar 21;4(126):126ra34. “Given the androgens are aromatized into estrogens, these results may be relevant to hair growth and alopecia in both men and women. Thus, these or similar pathways might be conserved in the skin and suggest that sex hormone regulation of Ptgds may contribute to the pathogenesis of AGA.” “…demonstrates elevated levels of PGD2 in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD2 as an inhibitor of hair growth in AGA and suggest the PGD2-GPR44 pathway as a potential target for treatment.”
  43. Bulun, S.E., et al. Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance. J Mol Endocrinol. 2000 Aug;25(1):35-42. “In contrast, aromatase is expressed aberrantly in endometriosis and is stimulated by prostaglandin E(2) (PGE(2)). This results in local production of estrogen, which induces PGE(2) formation and establishes a positive feedback cycle.”
  44. Greenhough, A., et al. The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis. 2009 Mar;30(3):377-86. doi: 10.1093/carcin/bgp014. Epub 2009 Jan 9. “It is widely accepted that alterations to cyclooxygenase-2 (COX-2) expression and the abundance of its enzymatic product prostaglandin E(2) (PGE(2)) have key roles in influencing the development of colorectal cancer.” “Future studies into the emerging players within the COX-2/PGE2 pathway may reveal novel approaches for more safely targeting this pathway for both cancer chemoprevention and therapy.”
  45. Cherkasskaia, M.D., et al. [Effect of prostaglandin E2 on energy metabolism in isolated rat liver mitochondria]. Vopr Med Khim. 1982 May-Jun;28(3):110-4. “In absence of EDTA prostaglandin E2, at concentrations of 5.6 microM and 56 microM, caused uncoupling of the oxidative phosphorylation and in presence of Ca2+—it caused uncoupling and inhibition of mitochondrial respiration, decrease in the rate of phosphorylation and in the ATPase reaction was well as in the efficiency of mitochondrial proton pump, connected with Ca2+ transport.”
  46. Kenji, A., et al. Human Hair Follicles: Metabolism and Control Mechanisms.  J. Soc. Cosmet. Chem., 21, 901-924 Dec. 9, 1970. “In 1958, Bullough and Laurence reported that mitosis in the hair bulb requires adequate supplies of oxygen and energy sources, such as glucose, fructose, and pyruvate.” “It was found that all of these inhibitors [e.g., cyanide, etc.] decreased CO2 production, and indication that the Krebs cycle is operative in the hair follicles…” “The activity of the Krebs cycle increases about 35% during the growth stage of the hair follicle…” “Thus, in the growing follicles, glucose assimilation produces not only sufficient, energy for the follicles function but also essential substances for the follicle to metabolism fatty acid, nucleic acid, and steroid hormones.”
  47. Goldberg, V.J., and Ramwell, P.W. Role of prostaglandins in reproduction. Physiol Rev. 1975 Jul;55(3):325-51.
  48. Denckla, W.D. Pituitary inhibitor of thyroxine. Fed Proc. 1975 Jan;34(1):96. “A description is given of a new pituitary function. It is suggested that the new function acts to decrease gradually the responsiveness of the peripheral tissues to thyroid hormones throughout life. It is suggested that the postulated relative hypothyroidism of older animals might contribute to their loss of viability.”
  49. 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.”
  50. Jordan, V.E. Protein status of the elderly as measured by dietary intake, hair tissue, and serum albumin. Am J Clin Nutr. 1976 May;29(5):522-8. “Serum albumin showed significant correlation with the protein content of the growing hair root bulbs. There was significant correlation between the percentage of growing hairs, their bulb diameters, and protein content, which in turn, correlated with the protein intake of the subject.”
  51. Pancharprateep, R., and Asawanonda, P. Insulin-like growth factor-1: roles in androgenetic alopecia. Exp Dermatol. 2014 Mar;23(3):216-8. “DP cells from balding scalp follicles were found to secrete significantly less IGF-1, IGFBP-2 and IGFBP-4 (P < 0.05) than their non-balding counterparts. Our data confirmed that the downregulation of IGF-1 may be one of the important mechanisms contributing to male pattern baldness.”
  52. Li, J., et al. Exogenous IGF-1 promotes hair growth by stimulating cell proliferation and down regulating TGF-β1 in C57BL/6 mice in vivo. Growth Horm IGF Res. 2014 Apr-Jun;24(2-3):89-94. “These observations suggest that IGF-1 is an effective stimulator of hair follicle development in wide-type mice in vivo and may be a promising drug candidate for baldness therapy.”
  53. Friesen, H.G., et al. Prolactin and growth hormone receptors. Ciba Found Symp. 1982;(90):263-78. “The two hormones prolactin and growth hormone exhibit considerable structural homology as well as exerting similar biological effects, especially the primate hormones. One effect of prolactin that deserves greater attention is its action on the immune system including the stimulation of growth of experimental lymphomas, both in vivo and in vitro.”
  54. Wilshire, G.B., et al. Diminished function of the somatotropic axis in older reproductive-aged women. J Clin Endocrinol Metab. 1995 Feb;80(2):608-13. “…insulin-like growth factor-I (IGF-I) levels in adults generally fall with age.”
  55. Mezey E. Insulin growth factor I and hypogonadism in cirrhosis. Hepatology. 2000 Mar;31(3):783-4. “Decreased serum IGF-1 concentrations are well documented in children with kwashiorkor, in malnourished adults, and after long-term fasting in obese male subjects.”
  56. Andersson, B., et al. Estrogen replacement therapy decreases hyperandrogenicity and improves glucose homeostasis and plasma lipids in postmenopausal women with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1997 Feb;82(2):638-43. “Blood glucose, glycosylated hemoglobin, c-peptide, total cholesterol, low-density lipoprotein cholesterol, and IGF-I decreased significantly (P < 0.01-P < 0.001), whereas high-density lipoprotein cholesterol rose (P < 0.001).”
  57. Martin, C. Endocrine Physiology. 1985. “Estrogens are among the best known of the growth stlimulants.”
  58. Vermeulen, A., et al. Estradiol in elderly men. Aging Male. 2002 Jun;5(2):98-102. “Free and bioavailable estradiol levels do decrease modestly with age as does the ratio of free testosterone to free estradiol, the latter testifying to the age-associated increased aromatization of testosterone. Estradiol levels are highly significantly positively related to body fat mass and more specifically to subcutaneous abdominal fat, but not to visceral (omental) fat. Indeed, aromatase activity in omental fat is only one-tenth of the activity in gluteal fat. Estrogens in males play an important role in the regulation of the gonadotropin feedback, several brain functions, bone maturation, regulation of bone resorption and in lipid metabolism. Moreover, they affect skin metabolism and are an important factor determining sex interest in man.”
  59. Santoro, N., et al. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab. 1996 Apr;81(4):1495-501. “We conclude that altered ovarian function in the perimenopause can be observed as early as age 43 yr and include hyperestrogenism, hypergonadotropism, and decreased luteal phase progesterone excretion. These hormonal alterations may well be responsible for the increased gynecological morbidity that characterizes this period of life.”
  60. Nagy, P., and Csaba, I.F. [Action of oestrogens on in vitro metabolism of trophoblast from human early pregnancy]. Zentralbl Gynakol. 1982;104(2):111-6. “Warburg’s manometric method was used to check the action of oestrone, oestradiol, and oestriol on aerobic and anaerobic glycolysis of placental respiration. Oestrogen concentrations of 10(-4) M were found to reduce oxygen consumption and to increase aerobic glycolysis. Such reduction of oxygen consumption was most strongly pronounced in connection with oestradiol, while the strongest rise in aerobic glycolysis took place in the wake of oestradiol and oestrone. Oestrogen action upon anaerobic glycolysis was variable, with the latter remaining unchanged by oestradiol, reduced in response to oestriol, and slightly increased by oestrone.”
  61. Suhane, S., and Ramanujan, V.K. Thyroid hormone differentially modulates Warburg phenotype in breast cancer cells. Biochem Biophys Res Commun. 2011 Oct 14;414(1):73-8. doi: 10.1016/j.bbrc.2011.09.024. Epub 2011 Sep 14. “Even though the role of thyroid hormone in modulating mitochondrial metabolism has been known, the current study accentuates the critical role it plays in modulating Warburg phenotype in breast cancer cells.” (Thanks Haidut)
  63. Kim, J.K., et al. Prevention of fat-induced insulin resistance by salicylate. “In summary, high-dose salicylate and inactivation of IKK-beta prevent fat-induced insulin resistance in skeletal muscle by blocking fat-induced defects in insulin signaling and action and represent a potentially novel class of therapeutic agents for type 2 diabetes.”
  64. Chen, Z.W., et al. [Effect of aspirin administration for the treatment of osteoporosis in ovariectomized rat model]. Zhonghua Yi Xue Za Zhi. 2011 Apr 5;91(13):925-9. “Aspirin can promote trabecular bone remodeling, improve three-dimensional structure of trabecular bone and increase bone density of cancellous in osteoporotic rats by stimulating bone formation. It may become a new drug for the treatment of osteoporosis.”
  65. Yamamoto, M., et al. Changes in thyroid hormones by treatment with aspirin and prednisolone in subacute thyroiditis with hyperthyroidism. Tohoku J Exp Med. 1979 Jan;127(1):85-95. “ Aspirin treatment, despite of initial increase in T3, had satisfactory effects on clinical signs and symptoms in subacute thyroiditis with no recurrence after withdrawal of the drug. It is concluded that aspirin treatment should be advocated not only in moderate but also in more severe cases of subacute thyroiditis.”
  66. Treib, J., et al. [Cerebral infarct in chronic acetylsalicylic acid poisoning]. Nervenarzt. 1996 Apr;67(4):333­4. “Salicylates can induce hemorrhage both by inhibiting platelet aggregation and especially in higher doses by vitamin K antagonism, leading to severe coagulopathy. The occurrence of an ischemic infarction, as presented in this case report, can be explained by a reduction of the vitamin K­dependent protein C level.”
  67. Senthillkumar, R., et al. Glycine modulates hepatic lipid accumulation in alcohol-induced liver injury. Pol J Pharmacol. 2003 Jul-Aug;55(4):603-11. “We studied the effect of administering glycine, a non-essential amino acid, on serum and tissue lipids in experimental hepatotoxic Wistar rats. All the rats were fed standard pellet diet. Hepatotoxicity was induced by administering ethanol (7.9 g kg(-1)) for 30 days by intragastric intubation. Control rats were given isocaloric glucose solution. Glycine was subsequently administered at a dose of 0.6 g kg(-1) every day by intragastric intubation for the next 30 days. Average body weight gain at the end of the total experimental period of 60 days was significantly lower in rats supplemented with alcohol, but improved on glycine treatment. Feeding alcohol significantly elevated the levels of cholesterol, phospholipids, free fatty acids and triglycerides in the serum, liver and brain as compared with those of the control rats. Subsequent glycine supplementation to alcohol-fed rats significantly lowered the serum and tissue lipid levels to near those of the control rats. Microscopic examination of alcohol-treated rat liver showed inflammatory cell infiltrates and fatty changes, which were alleviated on treatment with glycine. Alcohol-treated rat brain demonstrated edema, which was significantly lowered on treatment with glycine. In conclusion, this study shows that oral administration of glycine to alcohol-supplemented rats markedly reduced the accumulation of cholesterol, phospholipids, free fatty acids and triglycerides in the circulation, liver and brain, which was associated with a reversal of steatosis in the liver and edema in the brain.”
  68. Xu, F.L., et al. Glycine attenuates endotoxin-induced liver injury by downregulating TLR4 signaling in Kupffer cells. Am J Surg. 2008 Jul;196(1):139-48. “Dietary glycine improved survival rates and liver function in endotoxemic mice by regulating the production of proinflammatory or anti-inflammatory cytokines in liver. It attenuated liver injury by deactivating KCs through inhibiting TNF-alpha secretion and increasing IL-10 production. The downregulative effect of glycine on the endotoxin signaling pathway and TLR4/NF-kappaB/TNF-alpha may be a novel potential mechanism by which glycine inhibits KC activity.”
  69. Rose, M.L., et al. Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14,643. Carcinogenesis. 1999 Nov;20(11):2075-81. “These studies demonstrate that dietary glycine prevents the development of hepatic tumors caused by the peroxisome proliferator WY-14,643 consistent with the idea that it may be an effective chemopreventive agent.”
  70. Zeev, P. Edible Gelatin for Treating Hair Loss in both Men and Women patients for 19 Years in Clinical Practice. Aripam Medical Center, Ashdod, Israel 2012. “Dr. Zeev Pam, notes that from his many years of experience in his clinical practice that oral gelatin is a safe and effective treatment for hair loss for telogen effluvium and androgenic alopecia in both men and women as a single treatment or as a combination with other available treatments for hair loss.”
  71. Nilsson, L.H., and Hultman, E. Liver and muscle glycogen in man after glucose and fructose infusion. Scand J Clin Lab Invest. 1974 Feb;33(1):5-10.
  72. Acheson, K.J., et al. Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man. Am J Clin Nutr. 1988 Aug;48(2):240-7. “Glycogen storage capacity in man is approximately 15 g/kg body weight and can accommodate a gain of approximately 500 g before net lipid synthesis contributes to increasing body fat mass. When the glycogen stores are saturated, massive intakes of carbohydrate are disposed of by high carbohydrate-oxidation rates and substantial de novo lipid synthesis (150 g lipid/d using approximately 475 g CHO/d) without postabsorptive hyperglycemia.”
  73. Larson, A.R., et al. A prostaglandin D-synthase-positive mast cell gradient characterizes scalp patterning. J Cutan Pathol. 2014 Apr;41(4):364-9. “These data indicate that scalp is spatially programmed via mast cell prostaglandin D-synthase distribution in a manner reminiscent of the pattern seen in androgenetic alopecia.”
  74. Jin, Y., et al. Mast cells are early responders after hypoxia-ischemia in immature rat brain. Stroke. 2009 Sep;40(9):3107-12. “MCs are early responders to HI in neonatal brain. MC stabilization provides lasting protection and suggests a new target for therapeutic interventions.”
  75. Dix, R., et al. Activation of mast cells by systemic hypoxia, but not by local hypoxia, mediates increased leukocyte-endothelial adherence in cremaster venules. J Appl Physiol (1985). 2003 Dec;95(6):2495-502. Epub 2003 Aug 29. “Systemic hypoxia, produced by lowering inspired Po2, induces a rapid inflammation in several microcirculations, including cremaster muscle.” “The results suggest that mast cell stimulation occurs only when PaO2 is reduced, independent of cremaster PmO2, and support the idea of a mediator that is released during systemic hypoxia and initiates the inflammatory cascade.”
  76. Johansson, A., et al. Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy. Am J Pathol. 2010 Aug;177(2):1031-41. “Mast cells affect growth in various human tumors, but their role in prostate cancer (PC) is unclear. Here, we identify mast cells as independent prognostic markers in PC using a large cohort of untreated PC patients with a long follow-up. By analyzing mast cells in different tissue compartments, our data indicate that intratumoral and peritumoral mast cells have anti-opposed to protumor properties.” “Similar to the situation in men, mast cells infiltrated rat prostate tumors that relapsed after initially effective castration treatment, concurrent with a second wave of angiogenesis and an up-regulation of FGF-2. We conclude that mast cells are novel independent prognostic markers in PC and affect tumor progression in animals and patients. In addition, peritumoral mast cells provide FGF-2 to the tumor micro environment, which may contribute to their stimulating effect on angiogenesis.”
  77. Zhou, C., et al. Relationship Between Male Pattern Baldness and the Risk of Aggressive Prostate Cancer: An Analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. 2014. “Our analysis indicates that frontal plus moderate vertex baldness at age 45 years is associated with an increased risk of aggressive prostate cancer and supports the possibility of common pathophysiologic mechanisms.”
  78. Leav, I., et al. Prolactin Receptor Expression in the Developing Human Prostate and in Hyperplastic, Dysplastic, and Neoplastic Lesions. Am J Pathol. 1999 Mar; 154(3): 863–870. “Indirect evidence of possible PRL involvement in the development of benign prostatic hyperplasia (BPH) and/or carcinoma has come from reports that circulating hormone levels were significantly higher in older men when compared with those found in younger males. Moreover, patients with prostate cancer have been reported to have higher levels of plasma PRL than did age-matched controls, and high affinity PRL binding sites have been detected in normal, BPH, and neoplastic human prostate.”
  79. Arck, P.C., et al. Neuroimmunology of stress: skin takes center stage. J Invest Dermatol. 2006 Aug;126(8):1697-704. “Human mast cells are activated by a plethora of mast-cell secretagogues and other mediators. This includes the stress hormones ACTH and CRH, as skin mast cells express five CRH-R1 isoforms as well as CRH-R2α. Thus, skin mast cells not only are highly sensitive to modulation of their activities by classical stress hormones but also generate key stress hormones (at least CRH) themselves.”
  80. Strider, J.W., et al. Treatment of mast cells with carbon dioxide suppresses degranulation via a novel mechanism involving repression of increased intracellular calcium levels. Allergy. 2011 Mar;66(3):341-50. “Results from this study provide the first evidence of a unique regulatory mechanism by which CO2 inhibits mast cell degranulation and histamine release by repressing stimulated increases in intracellular calcium. Thus, our data provide a plausible explanation for the reported therapeutic benefit of noninhaled intranasal delivery of 100% CO2 to treat allergic rhinitis.”