HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014

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1 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Anterior Pituitary GH Liver IGF-1 Pancreas Insulin 2 Adrenal Glands (Cortex) DHEA Cortisol Aldosterone Males: 2 Testicles Testosterone Dihydrotestosterone (DHT) Females: 2 Ovaries Estrogens Progesterone 1

2 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 People age.. unnecessarily? = New, wellkept house Age 24, untreated = Age 64, untreated House not well cared of, not repaired 2

3 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 = Untreated very old person Ruin How can we partially or even near totally reverse the aging? Ideally = Age 64, untreated = Age 68 => Outlook of a treated age 24? 3

4 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Aim of Medicine: Make the patient as healthy as possible Aim of Reversing Aging Medicine: Make the patient as young as possible to be sure (s)he is at his (her) healthiest Less healthy Healthier Healthiest Age 55 Age 52 Age 58 Age 56 Age but looks as a 40-year old (15 years younger) but looks as a 30-year old (25 years younger) Aim of Medicine: Make the patient as healthy as possible Aim of Reversing Aging Medicine: Make the patient as young as possible to be sure (s)he is at his (her) healthiest Less healthy Healthier Healthiest Hormon e therapie s + Paleolith ic- type Diet Age 55 Age 52 Age 58 Age 56 Age but looks as a 40-year old (15 years younger) but looks as a 30-year old (25 years younger) 4

5 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Aim of Medicine: Make the patient as healthy as possible Aim of Reversing Aging Medicine: Make the patient as young as possible to be sure (s)he is at his (her) healthiest Less healthy Hormone therapies + Paleolithic - type Diet Healthier Hormone therapies + Paleolithic -type Diet + Nutritional therapies + Telmomerase activators Healthiest Age 55 Age 52 Age 58 Age 56 Age Stem cell therapy? but looks as a 40-year old (15 years younger) but looks as a 30-year old (25 years younger) Less healthy Hormone therapies + Paleolithic - type Diet Healthier Hormone therapies + Healthiest Age 55 Age 52 Age 58 Age 56 Age Cortisol 1. IGF-1- Growth hormone 2. Testosterone 2. Estradiol 3. Insulin (longacting) 5

6 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 human Growth Hormone Anterior Pituitary Growth Hormone MSH ACTH LH, FSH TSH 6

7 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Physical Aging by Growth hormone & IGF-1 deficiency Thin hair lacking volume Sex hormone, GH, IGF-1 deficiencies Shorter hair IGF-1/GH Forehead defic. Thin eyebrows (middle) GH, IGF-1 Wrinkles Cataract Melatonin, GH deficiencies Muscle hypotrophyigf-1/gh, testosterone, DHEA deficiencies Droopy upper/lower eyelids IGF-1/GH deficiencies AGING FACE IGF-1/GH & Sex hormone defic. Droopy nose tip Sagging cheeks Nasolabial fold IGF-1/GH deficiency Thinner lips (Insulin deficiency) Skinfolds under the chin Dry skin Thyroid, sex hormone, DHEA, GH deficiencies 7

8 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Growth hormone deficiency Psychic complaints appear mainly During the day: Exhausted, dramatizing, anxious => In the evening: worsens, complete exhaustion, anxious Passing bedtime hour aggravates all psychic complaints Whole day and evening worsens towards the More superior, relaxed mind Improved to spiritual consiousness Growth hormone Ene r-gy Hap pine ss Jo y Love Ser enit y Fir mn ess Irrit a bilit y Hat e Run s awa y Fear Para lyze d Sadness Cry -ing Dep ress ed Unha ppi ness Fat igu e 8

9 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 GH treatment: The change! BEFORE AFTER 2 months GH & 4 months TESTO GH treatment: The change! 9

10 HormoonWellness - Dr. Thierry Hertoghe 23 mei

11 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Magnesium citrate Mg => GH Mg therapy => GH 11

12 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Mg => serum GH Mg treatment => serum GH SUBJECTS: lactating dairy cows + feed intake RESULTS: (84% concentrate diet) serum Mg => increase of serum GH caused by feed intake g MgO or g of Mg(OH)2 supplements => Serum GH (vs controls) Emery RS, Luoma J, Liesman J, Thomas JW, Tucker HA, Chapin LT. Effect of serum magnesium and feed intake on serum growth hormone concentrations. J Dairy Sci Apr;69(4):

13 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Magnesium absorption Best absorbed: the chelated form of magnesium, such as magnesium citrate, glycinate or malate. This form is by your body. Step 2 Combine magnesium with calcium. The easiest way is to take a balanced formula of 1 part magnesium to 2 parts calcium. Step 3 Take vitamin C at the same time. It helps make magnesium more biologically available to your body. Step 4 Bathe in magnesium sulfate, better known as Epsom salts. The mineral can be absorbed through your skin. Step 5 Reduce or eliminate your consumption of soft drinks. Their high level of phosphates causes magnesium to be depleted from your body. Step 6 Lower your fat intake. A high fat intake will also cause magnesium to be depleted from your body. Mg content of oral supplements 13

14 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Potassium 14

15 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 K + => GH Potassium deficiency => GH Potassium therapy => GH 15

16 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Niacin 16

17 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Vit. B3 => HDL, LDL, TG HDL: Niacin => increased HDL levels over 25%, vs an increase of 13.3% due to gemfibrozil. LDL: Gemfibrozil actually raised LDL, while niacin slightly lowered this fraction. TG: Gemfibrozil lowered triglyceride levels by 40%, vs a 30% decrease from niacin. CCL: niacin resulted in an overall improvement in the lipid profile which exceeded that induced by gemfibrozil Guyton, John R., Blazing, Michael A., Hagar, James, et al. Extended-release niacin vs Gemfibrozil for the treatment of low levels of high density lipoprotein cholesterol. Arch Intern Med, 2000, 160: Vit. B3 => mortality These results support many previous studies on the use of niacin as a lipid-lowering nutrient. Ex.: in the Coronary Drug Project, which enrolled men with a previous myocardial infarction, niacin use => 26% decrease in 2 nd non-fatal heart attacks over a 6-yr period 11% decrease in total mortality after 15 yrs of follow up (Canner, et al, 1986) (Fig. 2). References: Canner, P.L., Berge, K.G., Wenger, N.K., et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol, 1986, 8: ; Dilman, V., and Dean, W. The Neuroendocrine Theory of Aging and Degenerative Disease, 1992, The Center for Bio-Gerontology, Pensacola; Guyton, John R., Blazing, Michael A., Hagar, James, et al. Extended-release niacin vs Gemfibrozil for the treatment of low levels of high density lipoprotein cholesterol. Arch Intern Med, 2000, 160: ; Horowitz, N. Link niacin to longevity after an MI. Medical Tribune, 1985, 26: 12, pp. 1, 17. Muntoni, S. Inhibition of fatty acid oxidation by biguanides: implication for metabolic physiopathology. Adv Lipid Res, 1974, 12: ; Quabbe, H.J., Ramek, W., and Luyckx, A.S. Growth hormone, cortisol and glucagon concentration during plasma free fatty acid depression. Different effects of nicotinic acid and an adenosine derivative. J Clin Endocr Metab, 1983, 57:

18 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Niacin deficiency => Pellagra = the disease caused by niacin deficiency => involves skin (photosensitivity), gastrointestinal tract central nervous system. progresses through dermatitis, diarrhea, depression & death. Pellagra was endemic in the southern USA (& many other parts of the world) in the early 1900s, partt. among children. It was found to be a dietary deficiency by Joseph Goldberger, a U.S. Public Health Service physician at about the time of the first world war. Pellagra was carried to Europe in the years following Columbus' discovery of the new world as maize (corn) was discovered & became the staple for Europe's poor. Vit. B3 treatment => GH 18

19 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Niacin => stimulates GH While extolling the benefits of niacin, one frequently overlooked side effect is that niacin = powerful releaser of growth hormone (Quabbe, et al, 1983) (Fig. 3). Quabbe & colleagues administered 500 mg niacin intravenously to humans => dramatic rise in GH. In a 2nd phase of their study, they simultaneously administered an infusion of fatty acids => the fat completely blunted any rise in growth hormone. CCL: anyone using niacin as a GH stimulant should take it on an empty stomach (glucose & insulin also inhibit growth hormone, as well as fatty acids). References: Quabbe, H.J., Ramek, W., and Luyckx, A.S. Growth hormone, cortisol and glucagon concentration during plasma free fatty acid depression. Different effects of nicotinic acid and an adenosine derivative. J Clin Endocr Metab, 1983, 57: Niacin: oral at bedtime Too Low Optimal dose Excess 0.1 g? g > 0.8 g? Mild to good GH response (only in lean subjects); no response in subjects > 1.5 x ideal weight Flush 20 ( histamine release w/ artery dilatation); Liver damage (timereleased forms from 0.8 g up) To optimize: Xanthinol nicotinate passes better the blood-brain barrier Klatz R. Grow Young with HGH. Harper & Collins 1997 Hertoghe T, Brussels,

20 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Vit. B3 => Flush Mechanism: niacin causes fatty acids in the skin => changed into rel. prostaglandins => open the blood vessels. If any part of this system is not working properly, the flush response does not occur such as in some chizophrenics schizophrenia healthy Patch test result from patient with schizophrenia (left) vs healthy High dose niacin is very safe: =>most frequent adverse effect = harmless flushing of the skin + itching => usually resolves over a few days or weeks of use. 3 ways of minimizing the flush: 1. Taking an aspirin 30 or so before the niacin => helps to reduce this effect. 2. To start with low doses ( mg) & gradually increase the dose as tolerated. 3. Use inositol hexanicotinate (IHN) another non-flushing form of. IHN, while a bit more costly than niacin, = effective in somewhat lower doses, thereby remaining cost effective 20

21 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Amino acids known to increase GH release L-Arginine mg L-Glutamine mg L-Ornithine mg L-Lysine mg Glycine mg Tryptophan 5 to 10 g 21

22 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 GH & arginine & obesity STIMULATION Lean Obese 22

23 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Arginine: oral 1h before exercise & sleeping Lower dose Optimal dose Excess 3 g 7 12 g > 20 g moderate Gh response Highest GH response (esp. in young adults yrs those w/ low body fat & high aerobic capacity) mechanism: inhibits somatostatin Lowest GH response, diarrhea enhances effects of GHRH when given together Matteini M et al. GH secretion by arginine stimulus: the effect of low doses and oral arginine administered before standard test. Bull Soc Ital Biol Exp. 1980; 56: 2254 Hertoghe T, Brussels,

24 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Glutamine: oral at bedtime Too Low Optimal dose Excess 0.5 g 2 g > 5 g good GH response (works also in older adults (32-64 yrs)), virtually no side effects Low Toxicity mechanism: stimulates GH secretion Welbourne T. Increased plasma bicarbonate and growth hormone after oral glutamine load. Am J Clin Nutr. 1995; 61: Hertoghe T, Brussels,

25 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Ornithine-alpha-ketoglutarate (OKG) => potently insulin, GH & IGF-1 in trauma patients Ornithine-alpha-ketoglutarate (OKG) = promising anticatabolic agent a. SUBJECTS:14adult, multiple trauma patients who were highly catabolic and hypermetabolic were studied. Whole-bodyprotein ((15)N glycine), fat (2 stage glycerol infusion) and glucose((3h)glucose) kinetics (t/o) and plasma parameters were measured (A) within48-60 h after injury before starting nutritional support and then (B) after 4days of enteral feeding. Group A (n=7, control) received a defined enteralformula (Two Cal HN, 1.4 times BEE calories) and Group B (n=7, OKG) receivedsame isonitrogenous diet replacing 2.62gN/d from the enteral diet by OKG-N (20gOKG/d). RESULTS (Mean+/-SEM): Protein turnover is significantly (P<==0.05)increased in OKG treated patients (4.68+/ vs 3.90+/-0.23, gp/kg/day) andglycerol turnover is decreased (0. 87+/-0.16 vs 1.46+/-0.16, micro mole/kg/min).glucose turnover is not changed. Significant (P<== 0.05) increases in serum levels of hormones (insulin, 44.2+/-8.4 vs 15.7+/-5.0 ulu/ml, GH 1.68+/-0.33 vs 0.92+/-0.16, ng/ml and IGF-1, 106+/-13 vs 75+/-18,ng/ml) and free amino acids (glutamine, 383+/-20 vs 306+/-25, Proline, 203+/-18vs 146+/-13 and ornithine, 164+/-27 vs 49+/-5 micro mole/l) are found in OKG treated patients, compared to non OKG patients. CONCLUSION: Increased hormonesecretion due to OKG and the rapid interaction between the metabolites of OKG atthe intermediary metabolism level may be responsible for altered substrate fuelkinetics. Jeevanandam M, Petersen SR. Substrate fuel kinetics in enterally fed trauma patients supplemented with ornithine alpha ketoglutarate. Clin Nutr Aug;18(4): Trauma Center, St. Joseph's Hospital and Medical Center, 350 West Thomas Road, Phoenix, Arizona 85013, USA. Ornithine : oral at bedtime Lower dose Optimal dose excess 1.5 g g > 10 g moderate Gh response Highest GH response (esp. in young adults yrs those w/ low body fat & high aerobic capacity) Lowest GH response, diarrhea mechanism: enhances GH release Other effects: regenerates the liver in animals Klatz R. Grow Young with HGH. Harper & Collins 1997 Hertoghe T, Brussels,

26 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 NUTRIENT DOSE to GH levels/activity DURATION Calcium 500 to 1500 mg/day elemental calcium before bedtime 4 to 8 months or permanently 4 to 8 months or Magnesium oral mg/day elemental magnesium permanently Potassium oral 0.5 to 3 g/day 1 to 12 months Vit. B3 oral 1 3 x 500 mg/day 2 to 6 months Vit. B6 oral 1 to 2 x mg/day pyridoxine; or active: mg/day Pyridoxal-5-phosphate 4 to 8 mo or permanently Saturated fatty ac. oral saturated coconut oil, butter, egg yolk permanently Arginine oral 2 to 7 grams per day for 2 to 3 months (7 4 to 12 months g/day to increase growth hormone) Glutamine oral 2 g/day for 2 to 3 months Tryptophan 0.5 to 2 grams before bedtime. If less sleep less 4 to 3 months => take it in the morning. Lysine 1 to 3 g/day 2 to 3 months Glycine 4 to 6 g/day 2 to 3 months Orninthine 2 to 6 g/day 2 to 3 months + 26

27 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Insulin-like Growth Factor 1 The liver => Secretes most of IGF-1 (Insulin-like Growth factor 1)) Liver IGF-1 27

28 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 IGF-1 Deficiency IGF-1 Excess 28

29 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Pancreas Insulin Glucagon 29

30 HormoonWellness - Dr. Thierry Hertoghe 23 mei

31 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 IGF-1 treatment => Magnesium rh IGF-1 & insulin => => serum erythrocytic Mg SUBJECTS: 3 fasting normotensive & 10 essential hypertensive subjects before & 30, 60, & 120 after incubation w/ a physiologically maximal dose of insulin (200 µu/ml) & w/ diff. doses of r human IGF-I ( nmol/l). TREATMENT: In normotensive subjects, IGF-I elevated Mg(i) (P <0.05) in a dose- & time-dep. fashion, as did insulin (P < 0.05). In hypertensive subjects, maximal Mg(i) responses to insulin, but not to IGF-I, were blunted [insulin, 163 to 177 µmol/l (P=NS); IGF-I, 164 to 190 µmol/l (P < 0.05)]. For insulin, but not for IGF-I,cellular Mg(i) responsiveness was closely & directly related to basal Mg(i)levels (insulin: r=0.72; P < 0.01; IGF-I: r=0.18; P=NS). blunted Mg (i)responses to insulin could be reversed by preincubation of hypertensive cells with IGF-I. CCL: 1) both IGF-I & insulin stimulate erythrocytemg(i) levels; 2) cellular Mg(i) responses to insulin, but not to IGF-I, depend onbasal Mg(i) levels, i.e. the higher the Mg(i) the greater the sensitivity toinsulin; and 3) IGF-I potentiates insulin-induced stimulation of Mg(i) at dosesthat themselves do not raise Mg(i). Dominguez LJ, Barbagallo M, Sowers JR, Resnick LM. Magnesium responsiveness to insulin and insulin-like growth factor I in erythrocytes from normotensive and hypertensive subjects. J Clin Endocrinol Metab Dec;83(12): Division of Endocrinology, Metabolism, and Hypertension, Wayne State University, Detroit, Michigan 48201, USA. 31

32 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Potassium IGF-1 Potassium treatment IGF-1 32

33 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Potassium => serum IGF-1 in young rats FACT: Growth retardation & impaired protein synthesis = major characteristics of potassium (K)-deficiency in animals & man. SUBJECTS: young rats. TREATMENT: K-depleted rats after 10 days on K-def.diet, 4 1/2-week-old (vs controls) - 54% serum potassium (s-k) -97% weight gain. Sign. length, tibia length, and muscle weight of soleus in animals were all significantly reduced compared with pair-fed controls. * -46% s-igf-i w/ growth retardation s-insulin showed no decrease. K-repletion in animals depleted for 7 days showed Complete normalization of s-k within 24 hours, sign. increase in both s-igf-i and weight. In 4-week-old rats maintained on K-deficient diet + variable K-content (1 to 260 mmol/kg) for 1 wk, a strong corr. between the K-content of fodder & s-igf-i could be established (r =.88, P <.001), as well as between s-igf-i ² weight gain (r =.90, P <.001).Furthermore, a stepwise reduction in basal s-gh was seen with the graded reduction of dietary K-content. Flyvbjerg A, Dørup I, Everts ME, Orskov H. Evidence that potassium deficiency induces growth retardation through reduced circulating levels of growth hormone and insulin-like growth factor I. Metabolism Aug;40(8): Medical Department M (Diabetes and Endocrinology), Aarhus Kommunehospital,Denmark. Potassium => serum IGF-1 in rats 33

34 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Vit. A => IGF-1 34

35 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Vit. A diet => serum IGF-1 in rats SUBJECTS: Male rats (3-wk-old) => Vitamin A-deficient diet for 11 wk d serum retinol & hepatic retinyl palmitate. Sign. body weight (p < 0.05) Sign. serum IGF-I than the rats fed the control diet. Approx. 40% lower levels of the IGF-I mrna in the liver & lungs. 2x IGF-I receptor (IGF-IR) mrna in the heart 2x IGFBP-6 mrna in the lungs did not alter the expression of IGF-II, IGFBP-1, IGFBP-3, IGFBP-4 or IGFBP-5 in all tissues VA-deficient rats => single inj. of retinoic acid (2 mg/rat) tissue IGF-I & IGF-IR gene expression did not change after 4or 8 h the expression of IGF-II, IGFBP-4, & IGFBP-6 mrnas in some tissues increased rapidly. Fu Z, Yoneyama M, Noguchi T, Kato H. Response of the insulin-like growth factor system to vitamin A depletion and repletion in rats. J Nutr Sci Vitaminol (Tokyo) Dec;48(6): Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi Bunkyo-ku, Tokyo ,Japan. Vit A interacts with IGF1 expression IGF-1 Weight IGF-1 Weight in Rats Response of the insulin-like growth factor system to vitamin A depletion and repletion in rats. J Nutr Sci Vitaminol (Tokyo) Dec;48(6): Fu Z, Yoneyama M, Noguchi T, Kato H. 35

36 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Vit. A treatment => IGF-1 Retinoic acid restores IGF1 in alcohol-reduced plasma IGF1 mrna IGF-1 IGF-1 IGF-1 IGF-1 mrna IGF-1 mrna IGF-1 Alcohol-reduced plasma IGF-I levels and hepatic IGF-I expression can be partially restored by retinoic acid supplementation in rats. Lian F, Chung J, Russell RM, Wang XD. J Nutr Nov;134(11):

37 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 serum vit. D => serum IGF-1 37

38 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 IGF1 POSITIVELY CORRELATED VIT D IN AGING MEN Only 25(OH)D and total testosterone are positively associated with serum IGF-I IGF1 regulates 25(OH)D3 in men FAT MASS regulates 25(OH)D3 in women IGF-I is a significant predictor of BMD at the total hip, femoral neck and femoral trochanter neck Relationship between 25-(OH) D3, the IGF-I system, leptin, anthropometric and body composition variables in a healthy, randomly selected population. Gomez JM, Maravall FJ, Gomez N, Navarro MA, Casamitjana R, Soler J.Horm Metab Res Jan;36(1): IGF-I and testosterone levels as predictors of bone mineral density in healthy, community-dwelling men. Rucker D, Ezzat S, Diamandi A, Khosravi J, Hanley DA. Clin Endocrinol (Oxf) Apr;60(4): Vit. D treatment => IGF-1 38

39 HormoonWellness - Dr. Thierry Hertoghe 23 mei µg/day CALCITRIOL => => serum IGF-1 I osteoporotic women SUBJECTS: 18 osteoporotic women [1,25(OH)2D3] => 2 doses (1µg/day & 2 µg/day) for 14 days The biological effectiveness of the treatment => controlled by serum intact parathyroid hormone TREATMENT: CALCITRIOL 1,25(OH)2 vitamin D3 vs before treatment sign. plasma IGF-I, beta 2 microglobulin, & serum osteocalcin => effects were only apparent after the higher dose of the drug (169 vs 134 ng/ml, P < 0.01; 2.08 vs 1.92 µg/ml, P < 0.05; & 8.5 vs 5.4 ng/ml, P < 0.01, resp.). CCL: exogenous 1,25(OH)2D3 => production of IGF-I & beta 2 microglobulin in osteoporotic patients in parallel to the marker of osteoblastic function, osteocalcin Zofková I, Kancheva RL, Bendlová B. Effect of 1,25(OH)2 vitamin D3 on circulating insulin-like growth factor-i and beta 2 microglobulin in patients with osteoporosis. Calcif Tissue Int Mar;60(3):236-9.Institute of Endocrinology, Prague I, Czech Republic. 39

40 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 VITAMIN D Vit. D converter Cholecalciferol (vit. D3) 1 µg 40 IU 1 IU µg Ergocalciferol (vit. D2) 1 µg 40 IU 1 IU µg Note: IU: International Units; mg: milligrams; mcg: micrograms 90 Vit. D converter VIT. D TYPE µg IU Cholecalciferol (vit. D3) 100 µg 4000 IU recommended Ergocalciferol (vit. D2) 100 µg 4000 IU VIT. D TYPE IU µg Cholecalciferol (vit. D3) 1000 IU 25 µg recommended Ergocalciferol (vit. D2) 1000 IU 25 µg Note: IU: International Units; mg: milligrams; mcg: micrograms

41 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 PUFA treatment => IGF-1 41

42 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 IGF1 BURN PATIENTS : FISH OIL IMPROVES SPEED & AMOUNT OF IGF1 RECOVERY Decreased serum insulin-like growth factor-i in burn patients: relationship with serum insulin-like growth factor binding protein-3 proteolysis and the influence of lipid composition in nutritional support. Abribat T, Nedelec B, Jobin Crit Care N, Garrel Med. DR Jul;28(7):

43 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Zinc treatment => IGF-1 Zinc treatment in 22 Children short stature - OVER 6 weeks IGF-1 IGF-1 IGF-BP-3 IGF-BP-3 Effect of zinc supplementation on growth hormone,igf1,igfbp3,somatomedin generation,alkaline phosphatase, osteocalcin and growth on prepubertal children with idiopathic short stature. Imamoglu,Bereket,Turan,Taga J Pediatr Endocrinol Metab 2005 Jan 18,

44 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Ratio IGF1/IGFBP3 bioavailability of IGF1 Direct stimulatory effect of Zinc Effect of zinc supplementation on growth hormone,igf1,igfbp3,somatomedin generation,alkaline phosphatase, osteocalcin and growth on prepubertal children with idiopathic short stature. Imamoglu,Bereket,Turan,Taga J Pediatr Endocrinol Metab 2005 Jan 18, Protein, zinc => increase IGF-1 SUBJECTS: 226 free-living healthy middle-aged & elderly men aged y; 24-h dietary telephone interviews performed over 1 yr RESULTS: We observed statistically significant positive associations between intakes of protein (P for trend = 0.001) & zinc (P for trend = 0.002)and serum IGF-I concentrations after adjusting for age. The difference in mean serum IGF-I for the highest vs the lowest quintile of intake was approx. + 17% (162 µg/l vs 139 µg/l) for protein & + 16% (166 µg/l vs 143 µg/l) for zinc. Consumption of red meat (P for trend = 0.05) & fish & seafood (P =0.07) was modestly positively associated with serum IGF-I. Other dietary factors were not associated with IGF-I concentrations. CCL: greater dietary intakes of protein, zinc, red meat, & fish & seafood => associated with higher serum IGF-I Larsson SC, Wolk K, Brismar K, Wolk A. Association of diet with serum insulin-like growth factor I in middle-aged and elderly men. Am J Clin Nutr May;81(5): Division of Nutritional Epidemiology, The National Institute of Environmental Medicine and Molecular Medicine, Unit of Endocrinology and Diabetes, Karolinska Institutet, Stockholm, Sweden. susanna.larsson@imm.ki.se 44

45 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Zinc stimulates growth hormone. More than meat?? 226 Free living healthy men ; yr PROTEIN MEAT/FISH ASSOCIATION OF DIET WITH SERUM INSULIN-LIKE GROWTH FACTOR 1 IN MIDDLE-AGED AND ELDERLY MEN. AM J CLIN NUTR 2005 MAY 81(5) LARSSON,WOLK,BRISMAR,WOLK,;division nutr epidemiology stockolm Sweden 45

46 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Carnitine treatment => IGF-1 L-Carnitine => IGF-1 in sows SUBJECTS: sows (female swine, pig) TREATMENT: L-Carnitine-treated sows => plasma IGF-I on day 80 of pregnancy (experiment 2, p <0.05) & on day 95 (experiment 1, p < 0.10), & plasma IGF-II on day 80 (experiment 2, p < 0.05) than control sows.. Doberenz J, Birkenfeld C, Kluge H, Eder K. Effects of L-carnitine supplementation in pregnant sows on plasma concentrations of insulin-like growth factors, various hormones and metabolites and chorion characteristics. J Anim Physiol Anim Nutr (Berl) Dec;90(11-12): Institut für Ernährungswissenschaften, Martin- Luther-Universität Halle-Wittenberg, Halle/Saale, Germany. 46

47 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 L-Carnitine => serum IGF-1 in chicks + adequate protein, not + low protein, nor excess CARN. SUBJECTS: chicks => diets + varying dietary protein (50, 200 & 400 g/kg) for 10 days Dietary L-Carnitine supplementation provided 0, 200, 500 & 1000 mg/kg. L-Carnitine as 500 or 1000 mg/kg => sign. improved body weight gain in birds & 400 g protein/kg diets => little influence on plasma IGF-I in birds + low protein (50 g/kg) diet. dietary L-Carnitine increased from 0 to 1000 mg/kg in the adequate protein (200g/kg) diet => plasma IGF-I also increased. dietary L-Carnitine content was > 500 mg/kg in the 400 g/kg protein group =>plasma IGF-I decreased with increasing dietary L-Carnitine content Note: Body weight change correlated sign. w/ change in plasma IGF-I in chicks + adequate dietary protein. CCL: the improvement in body weight gain caused by dietary L-Carnitine supplementation was achieved when chicks were given their dietary protein requirement, which may be partially explained by an increase in plasma IGF-I. Kita K, Kato S, Amanyaman M, Okumura J, Yokota H. Dietary L-carnitine increases plasma insulin-like growth factor-i concentration in chicks fed a diet with adequate dietary protein level. Br Poult Sci Mar;43(1): Laboratory of Grassland Science, University Farm, Graduate School of Bioagricultural Sciences, Nagoya University, Aichi, Japan. kitak@agr.nagoya-u.ac.jp Carnitine => serum IGF-1 in rats SUBJECTS: Diabetic rats RESULTS: Diabetic rats sign. lower carnitine in serum & liver vs normal rats. Carnitine treatment dose-dep. serum total carnitine concentrations dose-dep. serum Total IGF-I in serum from diabetic rats by carnitine treatment, but was stat. sign.only in the D200 group. restored serum total IGF-I in STZ-induced diabetic rats to nearly normal levels The expression of liver IGF-ImRNA was lower in diabetic rats than in normal rats => increased by L-Carnitine treatment. no effect on the levels of IGF-II in serum, liver, and kidney. Heo YR, Kang CW, Cha YS. L-Carnitine changes the levels of insulin-like growth factors (IGFs) and IGF binding proteins in streptozotocin-induced diabetic rat. J Nutr Sci Vitaminol (Tokyo) Oct;47(5): Department of Food Science & Human Nutrition and Institute for Molecular Biology and Genetics, Chonbuk National University, Chonju, Korea. 47

48 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Acetyl-L-Carnitine (3 g/day) => serum IGF-1 SUBJECTS: 11 asymptomatic, HIV-1-infected subjects TREATMENT: Acetyl-L-Carnitine (3 g/day) for 5 months substantial impact on the main immunologic abnormality associated with HIV infection, loss of CD4 cells, by rate of apoptotic lymphocyte death. 2 impt mechanisms underlying the observed antiapoptotic effects of Acetyl-L-Carnitine ceramide generation serum IGF-1, a major survival factor able to protect cells from apoptosis by different stimuli & conditions Di Marzio L, Moretti S, D'Alò S, Zazzeroni F, Marcellini S, Smacchia C, Alesse E, Cifone MG, De Simone C. Acetyl-L-carnitine administration increases insulin-like growth factor 1 levels in asymptomatic HIV-1-infected subjects: correlation with its suppressive effect on lymphocyte apoptosis and ceramide generation. Clin Immunol Jul;92(1): Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy. 48

49 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Creatine treatment => IGF-1 Resistance training & Creatine => muscle IGF-1 in young adults SUBJECTS: 24 young men & 18 young women + minimal resistanceexercise-training experience (=1 year) + at least 30 min of structured physical activity (i.e., walking, jogging,cycling) 3-5 x/wk => supplement with creatine (CR: 0.25 g/kg lean-tissue mass for 7 days; 0.06 g/kg lean-tissue mass for 49 days; n=22, 12 males, 10 female) or isocaloric placebo (PL: n=20, 12 male, 8 female) and engage in a whole-body resistance-exercise training program for 8 wk. 18 = vegetarians (lacto-ovo or vegan; CR: 5 male, 5 female; PL: 3 male, 5 female) => Muscle biopsies (vastus lateralis) Resistance-exercise training (RET) intramuscular IGF-I content by 67%,=>greater accumulation with creatine supplementation (CR) (+78%) than placebo (+54%; p=.06). no diff. in IGF-I between vegetarians & nonvegetarians. CCL: Creatine supplementation during resistance-exercise training => intramuscular IGF-I in healthy men & women, indep. of habitual diet. Burke DG, Candow DG, Chilibeck PD, MacNeil LG, Roy BD, Tarnopolsky MA, Ziegenfuss T. Effect of creatine supplementation and resistance-exercise training on muscle insulin-like growth factor in young adults. Int J Sport Nutr Exerc Metab Aug;18(4): Department of Human Kinetics, St. Francis Xavier University, Antigonish, NS, Canada. 49

50 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 NUTRIENT DOSE to IGF-1 levels/activity DURATION Calcium 500 to 1500 mg/day elem. calcium prior bed 4 to 8 months Magnesium oral mg/day elemental magnesium 4 to 8 months Phosphorus oral g/day of Na/K+ phosphate; animal food. 4 to 8 months Potassium oral 0.5 to 3 g/day 1 to12 months Vit. A (retinol) oral to IU/day 4-8 months Vit. B7 (biotin) 2 mg/day; hair regrowth: 3x 2mg/wk IM inj. (18x) 4 to 8 months Vit. D3 (cholecalciferol) oral 1000 to 4000 IU/day or; IU/ 3-4 mo 4 to 8 months Vit. E (?) Oral mg/day (mixed tocpherols & tocotrienols 4 to 8 months oral 2-4 g/day fish oil for EPA and DHA or 6 to 8 months Omega-3 PUFA 1/2 table/souppoon/day of rapeseed or flaxseed oil Iron oral mg/day elem.iron (± 500 mg complexed) 2 to 12 months Manganese Oral 10 to 50 mg/day Zinc oral 50 mg/day zinc citrate or sulphate prior bed 4 to 8 months Carnitine oral L-Carnitine: 3 (women) to 4 (men) g/day; 4 to 8 months oral Acetyl-L-Carnitine: 2 (women) to 3 (men) g/day Glutamine oral 2 g/day 2 to 8 months Creatine oral 3 to 10 g/day 1 to 3 months 50

51 HormoonWellness - Dr. Thierry Hertoghe 23 mei

52 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Insulin therapy => plasma amino acids in old as in young men STUDY: healthy postabsorptive young (n = 5, mean age, 25 years) elderly (n=5, mean age, 76 years) men RESULTS: Glucose disposal rates adjusted for lean body mass (LBM) were lower in the elderly than in the young at the 6, 10, and 30 mu insulin infusion rates & similar in the two age groups in the 400 mu studies. Insulin dose-depe. in 8 of 10 plasma amino acids & not influenced by age. an insulin dose-depe. in plasma leucine flux which was similar in both age groups. Fukagawa NK, Minaker KL, Rowe JW, Matthews DE, Bier DM, Young VR. Glucose and amino acid metabolism in aging man: differential effects of insulin. Metabolism Apr;37(4): Department of Applied Biological Sciences, Massachusetts Institute of Technology, Cambridge. Insulin => speed of amino acid uptake in the fibroblasts MATERIAL: cultured human fibroblasts. INFO: Among the 6amino acid transport systems operating in cultured human fibroblasts => 2systems (A and X-C) are strongly stimulated by insulin & 4(ASC, X-AG, y+ and L) are essentially not sensitive to the presence of the hormone in the incubation medium. RESULTS: The hormonal stimulation of system A and system X-C => became significant after 3 h of incubation & increased up to 12 h. The stimulatory effect was related to insulin concentration, with a halfmaximal stimulation at 10(-9) M hormone concentration. Insulin enhanced transport activity by increasing the maximal velocity (Vmax) of transport, without significant changes in Km values. Longo N, Franchi-Gazzola R, Bussolati O, Dall'Asta V, Foà PP, Guidotti GG, Gazzola GC. Effect of insulin on the activity of amino acid transport systems in cultured human fibroblasts. Biochim Biophys Acta Feb 21;844(2):

53 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Insulin excess => <= Insulin deficit Insulin Deficient Insulin Excess Insulin Sufficient 53

54 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Vit. E in lower half of reference => type 2 Diabetes mellitus 54

55 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Vit. E treatment => insulin production Vit. E => pancreatic insulinproduction in type 2 diabetes SUBJECTS: 41 patients + type II diabetes mellitus => 4 groups: (1) diets, (2) predian, (3) glibenclamide, & (4) sugar-reducing drugs & insulin => All patients & 1200 mg/day vit. E RESULTS: Vit. E in doses pancreatic insulin-production conducive to normalization of lipid peroxidation no matter what kind of therapy is administered. Balabolkin MI, Mikhailova EV, Kniazeva AP, Pankova SS. [Effect of high doses of tocopherol on the processes of lipid peroxidation and insulin secretion in patients with non-insulin-dependent diabetes mellitus] Probl Endokrinol (Mosk) May-Jun;40(3):

56 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Vit. E + Vit. B3 Combination treatment => Delays type 1 Diabetes (Human study) Vit. E => delays diabetes type 1 in mice SUBJECTS: non-obese diabetic (NOD) mice => treated from 3 weeks of age until 30 weeks of age + vit. E-rich diet or control diet RESULTS: Vit. E did not reduce the incidence of diabetes (type 1) by 30 wks of age did sign. delay the onset of the disease (p <0.01) no diff. in the degree of lymphocytic infiltration of the pancreas (insulitis) with respect to control mice. CCL: Vitamin E delays diabetes onset in NOD mice without having an apparent effect on the autoimmune process Beales PE, Williams AJ, Albertini MC, Pozzilli P. Vitamin E delays diabetes onset in the non-obese diabetic mouse. Horm Metab Res Oct;26(10): Department of Diabetes and Metabolism, St. Bartholomew's Hospital, London, United Kingdom 56

57 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Vit. D supplements => Hyperglycaemia & Diabetes I Vit. D in infancy => type 1 diabetes 57

58 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Vit. D treatment => (Human study) Vit. D3 => insulin secretion 58

59 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 L-Arginine Treatment => C-peptide production (Human studies) Arginine => C-peptide peak response 59

60 HormoonWellness - Dr. Thierry Hertoghe 23 mei

61 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Adrenal cortex Adrenal medulla... 2 Adrenal Glands (Cortex) DHEA Cortisol Aldosterone Adrenal cortex Adrenal medulla Cortisol => provides energy, takes inflammation away DHEA => builds up, protects against cortisol catabolism Aldosterone => keeps blood pressure up /water in the body 61

62 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Cortisol Deficiency Adequate Cortisol Cortisol deficiency Psychic complaints appear mainly at moment of At moments & in the evening: Nervous, irritable, tensed, tired person stress or standing up 7h 19h 23h In between: Kind, extrovert person 62

63 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 More combative mind, punch Improved earth-to-earth consiousness Cortisol Ene r-gy Hap pine ss Jo y Love Ser enit y Fir mn ess Irrit a bilit y Hat e Run s awa y Fear Para lyze d Sadness Cry -ing Dep ress ed Unha ppi ness (++) Fat igu e Adrenal gland Cortisol 63

64 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 To boost Cortisol & other Adrenal hormones => a good understanding of Minerals Example of Marathon runnining 64

65 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Lack of Sodium = Global (Mental + Muscular) & Diffuse (all over) fatigue : + drowsiness 65

66 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Sodium => Cortisol sodium => urinary Cortisol, but similar serum ACTH & Cortisol SUBJECTS: 10 normal control subjects => 4 days of low sodium diet (intake 40 meq/day = 0.9 g/day) & after 6 days of high sodium diet (intake 320 meq/day = 7.36 g/day)). TREATMENT: high sodium diet (8x higher in Na, vs low sodium diet) 1.5x urinary cortisol from 26.2 to 36.8 µg/day similar plasma ACTH & serum cortisol measured every 2 h for a 24- h period CCL: altered handling of cortisol by kidneys during high salt intak. Wambach G, Bleienheuft C, Bönner G. Sodium loading raises urinary cortisol in man. J Endocrinol Invest Jun;9(3):

67 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Sodium treatment => Cortisol Sodium lactate IV => cortisol + panic attack SUBJECTS: 103 patients + panic disorder or agoraphobia + panic attacks, & 32 normal controls. TREATMENT: Sodium lactate infusions => panic attacks in patients + panic disorder, but not in normal controls - Baseline cortisol levels did not distinguish early panickers from nonpanickers & controls, but late panickers - sign. elevated baseline cortisol levels. - In addition, a higher % of late panickers => increase in cortisol during the baseline period vs the other groups. early panickers - sign. greater somatic distress as measured by the Acute Panic inventory. infusion of 0.5 mol/l of sodium lactate - no increase in cortisol with lactate-induced panic - cortisol levels fell sign. during the lactate infusion in all groups. CCL: Cortisol elevation occurred + moderate anxiety but not + severe panic anxiety. => different pathophysiologic mechanisms. Hollander E, Liebowitz MR, Gorman JM, Cohen B, Fyer A, Klein DF. Cortisol and sodium lactate-induced panic. Arch Gen Psychiatry Feb;46(2): Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY. 67

68 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Lack of Magnesium = Cramps in legs & feet 68

69 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Mg supplements alone => ACTH Mg + Exercise => resting serum Cortisol SUBJECTS: Supplementation with 10 mg of magnesium (as magnesiumsulfate) per kilogram of body weight. & exercise & magnesium supplements => sign. ACTH increases (p < 0.05). increased cortisol in training subjects + supplements (p <0.05) but not so in subjects that either trained or received magnesium supplements in an independent manner. higher cortisol levels measured in resting individuals were in the supplemented and non-supplemented athletes than those in sedentary subjects (p < 0.05). CCL: exercise &/or magnesium supplementation => rise of ACTH, whereas cortisol is increased only as a result of combined exhaustion and magnesium supplements. Cinar V, Mogulkoc R, Baltaci AK, Polat Y. Adrenocorticotropic hormone and cortisol levels in athletes and sedentary subjects at rest and exhaustion: effects of magnesium supplementation. Biol Trace Elem Res Mar;121(3): Karaman High School of Physical Education and Sport, Selcuk University, Karaman, Turkey. bsyovedat@yahoo.com Mg => serum cortisol & prevents the serum cortisol during exercise in healthy men SUBJECTS: 9 healthy men => one hour ergometer exercise MG TREATMENT: after 14 day magnesium aspartate supplementation NO observation of the usual aldosterone & cortisol increase during exercise sign. lower. serum cortisol Na & K in plasma increased during the exercise; these changes were not affected by Mg. The Mg concentration was elevated in plasma and erythrocytes During the ergometer course plasma Mg was unchanged but decreased sign. in the redblood cells. Mg and K concentration in sweat decreased during the exercise. No influence of Mg on urinary electrolyte excretion was observed. Golf SW, Happel O, Graef V, Seim KE. Plasma aldosterone, cortisol and electrolyte concentrations in physical exercise after magnesium supplementation. J Clin Chem Clin Biochem Nov;22(11):

70 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Calcium treatment => Cortisol 70

71 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Calcium => serum ACTH in humans => serum cortisol & aldosterone SUBJECTS: 4 normal subjects, one patient + hypoparathyroidism & one patient + hypothyroidism 6 normal subjects and 4thyroidectomized patients as controls TREATMENT: iv calcium gluconate a decrease in plasma renin activity but only in the normal subjects. higher Plasma ACTH, cortisol & aldosterone were when calcium was administered. Plasma ACTH and cortisol responses to calcium were abolished whereas plasma aldosterone response persisted in 2 normal subjects pre-treated + dexamethasone. Plasma renin activity was not statistically different whether or not calcium had been injected in the subjects studied twice. CCL: direct effect ofcalcium on ACTH and aldosterone secretion which is not mediated by calcitonin & parathyroid hormone. The stimulatory effect of calcium on cortisol secretion depends on the increase in plasma ACTH. Isaac R, Raymond JP, Rainfray M, Ardaillou R. Effects of an acute calcium load on plasma ACTH, cortisol, aldosterone and renin activity in man. Acta Endocrinol (Copenh) Feb;105(2):

72 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Lack of Potassium = Fatigue in lower legs Potassium => Cortisol 72

73 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Potassium treatment => urinary sodium & water excretion => serum Sodium => serum cortisol 73

74 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Vit. C treatment => Cortisol Vit. C => serum ACTH & cortisol in a healthy man SUBJECTS: a healthy male volunteer. TREATMENT: Vitamin C infusion initial to moderate stages :distinct plasma cortisol & vit. C from the circulation middle stage a small plasma cortisol terminal stage => skyrocket-like plasma ACTH & cortisol Methylprednisolone in vit. C infusion initial to moderate stages suppressed the depletion of plasma vitamin C & cortisol of the initial tomoderate stages. middle stage: No effect on the small surge of plasma cortisol. terminal stage: completely suppressed the emergence of the plasma ACTH/cortisol surges of the terminal stage Kodama M, Kodama T, Murakami M, Kodama M. Vitamin C infusion treatment enhances cortisol production of the adrenal via the pituitary ACTH route. In Vivo Nov-Dec;8(6): Kodama Research Institute of Preventive Medicine, Nagoya, Japan. 74

75 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Vit. C => cortisol production & delays its turnover in rats FACT: effect of vitamin C on adrenal glucocorticoid prod. repeatedly observed in human experiments SUBJECTS: scurvy-prone ODS rats vs scurvy-resistant Wistar rats PRETREATMENT: vit. C (ascobic acid) intraperitoneally release of endogenous glucocorticoid delay the turnover of the tracer cortisol in plasma. the effect of vitamin C = of physiological significance. The responses of the adrenal glands, testes & liver to vitamin C pretreatment were generally more distinct in scurvy-prone ODS rats than in Wistar rats, but varied from one organ to another. Kodama M, Inoue F, Kodama T, Kodama M. Intraperitoneal administration of ascorbic acid delays the turnover of 3H-labelled cortisol in the plasma of an ODS rat, but not in the Wistar rat. Evidence in support of the cardinal role of vitamin C in the progression of glucocorticoid synthesis. In Vivo Jan-Feb;10(1): Biophysics Division, National Cancer Center Research Institute, Tokyo, Japan. 75

76 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Acetyl-L-Carnitine treatment => Cortisol Acetyl-L-Carnitine => serum cortisol Acetyl-L-Carnitine => acutely administered => raises serum beta-endorphin & cortisol in humans Martignoni E, Facchinetti F, Sances G, Petraglia F, Nappi G, Genazzani AR. Acetyl-Lcarnitine acutely administered raises beta-endorphin and cortisol plasma levels in humans. Clin Neuropharmacol Oct;11(5):472-7.Department of Neurology, C. Mondino Foundation, University of Pavia, Italy. 76

77 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Glutamate treatment => Corticosterone Neonatal Glutamate => corticosterone in mice SUBJECTS: Male mice TREATMENT: Neonatal administration of sodium glutamate (4 mg/g) on (postnatal days 1, 3, 5, 7, & 9) numbers of square crossings, vertical rearings, excursions to the center, and the time spent in the center in adulthood, vs mice + physiological saline In the light-dark test, time spent by mice in the light sector, but did not differ from that in intact animals. In the acoustic startle reflex test, startle amplitude but had no effect onthe magnitude of prestimulus inhibition. sexual motivation, physiological saline producing a tendency to decreased sexual motivation. 4x basal blood corticosterone in adult males, while physiological saline had no effect. CCL: neonatal sodium glutamate => decreases motor and investigative activity, anxiety, and sexual motivation in adult male mice => increases basal corticosterone. Physiological saline increased all these parameters apart from sexual motivation, though this was not associated with changes in basal corticosterone. Kuznetsova EG, Amstislavskaya TG, Bulygina VV, Il'nitskaya SI, Tibeikina MA, Skrinskaya YA. Effects of administration of sodium glutamate during the neonatal period on behavior and blood corticosterone levels in male mice. Neurosci Behav Physiol Oct;37(8): Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, Russia. 77

78 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Omega-3 (esp. EPA) Cortisol Omega-6 treatment (esp. DHGLA) Cortisol 78

79 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 PUFA: EPA, (DHA) & ARA => cortisol prod. DHGLA => cortisol prod. in fish interrenal cells SUBJECTS : fish => in vitro studies of sea bream interrenal cells TREATMENT: essential fatty acids on ACTH-ind. cortisol prod. /release Arachidonic acid (ARA) & part. eicosapentaenoic acid (EPA) => cortisol production in sea bream interrenal cells Indometacin (INDO= eicosanoidproduction inhibitor) => the increased cortisol prod. induced by EPA & ARA, suggesting mediation by their cyclooxygenase-derived products Docosahexaenoic acid => cortisol prod. to a lesser extent than that caused by EPA or ARA, but the inhibitory effect of INDO was not as marked as it was for the other fatty acids. dihomogammalinolenic acid => cortisol production = inhibitor effect of this fatty acid on cortisol secretion. Ganga R, Tort L, Acerete L, Montero D, Izquierdo MS. Modulation of ACTH-induced cortisol release by polyunsaturated fatty acids in interrenal cells from gilthead seabream, Sparus aurata. J Endocrinol Jul;190(1):39-45.Grupo de Investigación en Acuicultura, Instituto Canario de Ciencias Marinas, PO Box 56, Telde, Las Palmas, Canary Islands, Spain. rgaqua2003@yahoo.fr 79

80 HormoonWellness - Dr. Thierry Hertoghe 23 mei 2014 Cortisol + NUTRIENT DOSE to CORTISOL levels/activity DURATION Calcium 500 to 1500 mg/day elemental calcium before bedtime 4 to 8 months or permanently Potassium oral 0.5 to 3 g/day 1 to 12 months Magnesium (?) Vit. B5 oral mg/day elemental magnesium oral 1 to 3 x 100 mg daily as oral capsules scalp hair growth: 3 x 500 mg IM inj. of vit. B5 4 to 8 months or permanently 2 to 8 months Vit. C (?) oral 1 to 2 g/day 4 to 8 months Vit. K1 (pylloquinone) oral 1-10 mg/day of safe (phylloquinone) 2 to 12 months Omega-3 PUFA oral 2-4 g/day fish oil for EPA and DHA or 6 to 8 months (EPA, (DHA)) 1/2 table/souppoon/day of rapeseed or flaxseed oil Saturated fatty ac. oral saturated coconut oil, butter, egg yolk permanently Cholesterol Carnitine oral : consume more foods rich in cholesterol oral L-carnitine: 3 (women) to 4 (men) g/day; oral Acetyl-L-carnitine: 2 (women) to 3 (men) g/day 4 to 8 months or permanently 4 to 8 months Cortisol - NUTRIENT DOSE to excess CORTISOL DURATION Sodium oral 1 to 3 g/day of sodium (1 g/day per 1000 kcal 1 to 12 months consumed per day) 4 to 8 months or Magnesium (?) oral mg/day elemental magnesium permanently Vit. B5 100 mg/day for; Migraines: 400 mg/day 2 to 6 months Vit. C (?) oral 1 to 2 g/day 4 to 8 months Omega-6 PUFA oral 500 to 1000 mg/day of borage oil or evening 4 to 8 months (DHGLA) primrose oil (combine w/ vit. E mg/day) oral 0.2 to 2 mg/day, preferably nicotinate or 4 to 12 months Chromium tripicolinate chromium; active = GTF chromium (Glucose Tolerance Factor =chromium nicotinate) Zinc oral 50 mg/day zinc citrate/sulphate prior bed 4 to 8 months Arginine oral 2 to 7 grams per day for 2 to 3 months (7 4 to 12 months g/day to increase growth hormone) Lysine oral 2.5 g g/day 2 to 8 months 80