Nutritional Considerations of Endocrinology Part 2 Men s Health. Presented by: Dr. Ron Grabowski May 20 th 2010

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1 Nutritional Considerations of Endocrinology Part 2 Men s Health Presented by: Dr. Ron Grabowski May 20 th 2010 May 21, 2010

2 Nutritional Considerations of Endocrinology Part 2 Men s Health Presented by: Dr. Ron Grabowski May 20 th 2010 May 21, 2010

3 Thyroid Function and Mineral Status Zinc Selenium Iron Iodine May 21, 2010 Presentation Title 3

4 Zinc and the Thyroid Gland Protein synthesis Involved in T3 binding to its nuclear receptor (Miyamoto et al. 1991). In a zinc depletion-repletion study conducted in humans, Wada and King (1986) observed that circulating TSH, total T4 and free T4 tended to decrease during the depletion phase, returning to control levels after zinc repletion. Zinc deficiency can indirectly affect thyroid hormone status by decreasing energy intakes. May 21, 2010 Presentation Title 4

5 Zinc Status Serum retinol has been positively associated with serum zinc. In some studies, children with serum retinol <1.05 umol/l had an almost two-fold greater risk of being zinc deficient compared to those with serum retinol levels indicative of adequate vitamin A status. Serum albumin concentrations have also correlated positively with serum zinc concentrations. Approximately 70% of zinc is transported in the serum bound to albumin. Males have shown to have an almost two-fold greater risk of being zinc deficient than females, possibly a reflection of the higher zinc requirements of males than females because of their higher lean body mass and growth rate (Hotz and Brown 2004). May 21, 2010 Presentation Title 5

6 Zinc Absorption and Excretion Studies have shown that phytate interferes with zinc absorption both from vegetable and animal protein sources. In addition to phytate, vegetables contain other organic compounds, e.g., phaeophytin, a degradation product of chlorophyll, which may bind metals and make them unavailable. Calcium may increase the inhibitory effect of phytate on zinc absorption. The normal zinc content of sweat is approximately 115 ug/100ml. A normal individual might lose 5 or more mg of zinc/day in sweat. May 21, 2010 Presentation Title 6

7 Zinc and Hyperthyroidism High serum Zn values have been reported in hyperthyroidism and serum Zn concentrations have been noted to correlate well with T3 and T4 levels. The present study confirms that the red blood cell Zn concentration is decreased in thyrotoxic patients and increased in hypothyroid patients. Thyroxine administration to rats significantly enhanced the rate of Zn-turnover and altered its distribution in various organs leading to an almost 50% depletion in soft tissue Zn. A higher than normal urinary Zn excretion in hyperthyroidism has been reported by Bremner and Fell and Nishi et al; this may result from an increased extracellular fluid Zn loss. Excess thyroid hormone may result in the mobilization of Zn from tissues such as erythrocytes, bone, and muscle by increased catabolism. May 21, 2010 Presentation Title 7

8 Prealbumin (PA) and Retinol Binding Protein (RBP) It is well known that Zn, RBP, and T4 to some extent, exist in blood complexed to PA which is a carrier for both thyroid hormone and Zn in the plasma. Zn is considered to play a regulatory role in the release of RBP from the liver. Morley et al noted that serum Zn levels correlated positively with T3 but not with T4 and that RBP and PA levels correlated positively with T3 in patients with alcoholic cirrhosis. May 21, 2010 Presentation Title 8

9 Iodine in Thyroid Disease Iodine is an essential nutrient for man. Its main function is concerned with the formation of the thyroid hormones. After absorption from the intestine, iodine is transported in the blood as the iodide. Thyroid cell for iodide causes it to be trapped there, oxidized to elemental iodine, and then incorporated into an amino acid, tyrosine, which in a series of coupling reactions becomes the active hormones, triiodothyronine (T3) and tetraiodothyronine (thyroxine; T4). The optimal adult requirement for iodine is approximately ug/day. In the United States, iodized salt contains 0.01% potassium iodide. Thus the requirement could easily be satisfied on an intake of 3-4 g salt daily. Conditions such as pregnancy, lactation, infection, puberty, and acromegaly increase requirements considerably above those of the normal adult. May 21, 2010 Presentation Title 9

10 Iodine Status There has been a high prevalence of both suboptimal iodine and zinc status among the children concomitant with the relatively high levels of anemia and marginal vitamin A deficiency (Thurlow et al. 2005). Mild to moderate iodine deficiency can have detrimental effects in children, causing impairments in both neuropsychological and physical development (van den Briel et al. 2000; WHO/UNICEF/ICCIDD, 2001). May 21, 2010 Presentation Title 10

11 Iodine, Selenium and Zinc Current evidence indicates that the simultaneous occurrence of nutritional deficiencies of more than one of these micronutrients could be more common than previously considered. (Diplock 1992, Vanderpas et at. 1993). Combined deficiency of selenium and iodine has been suggested as a potential determining factor in the development of the myxedematous or nervous form of endemic cretinism. (Goyens et al. 1987, Vanderpas et al. 1990). Two-and three-way nutrient interaction may have distinct manifestations in thyroid function. May 21, 2010 Presentation Title 11

12 Selenium and the Thyroid Gland Participates in the extrathyroidal deiodination of T4 to the active form T3 (Arthur et at. 1993). Component of deiodinase type I, which transforms T4 into T3 in liver, kidney, muscle and thyroid. Evidence suggests that deiodinases type II and Type III may also be selenium dependent (Arthur 1997). Deiodinase type II plays an important role in providing intracellular T3 to the brain and pituitary. Selenium also plays a role in oxidative stress control at the thyroid as a component of the enzyme glutathione peroxidase. May 21, 2010 Presentation Title 12

13 Histologic Evaluations Thyroid glands of selenium-deficient animals showed an active fibrotic process in which the inflammatory reaction and excess of transforming growth factor- play a key role. Contempre et al. (1996) The most severe morphologic alteration of the thyroid cell were caused by Zn deficiency alone or in combination with the lack of Se. May 21, 2010 Presentation Title 13

14 Thyrotoxicosis and Vitamins Increases the need for almost all the vitamins especially pyridoxine, pantothenic acid, and thiamin. A deficiency of pyridoxine in a normal animal depresses the uptake of radioactive iodine by the thyroid gland. If pyridoxine deficiency exists, gastric secretion decreases with a subsequent decline in vitamin B12 absorption. Mohamed and Roberts have reported that seven of ten thyrotoxic patients showed an abnormality in the breakdown of histidine to glutamic acid. This reaction has been shown to be folate dependent and suggests that a relative deficiency of folic acid exists in the thyrotoxic patient. Excessive thyroid secretion has been demonstrated to increase the need for vitamin A, riboflavin, ascorbic acid, vitamin D, choline, and perhaps vitamin E. May 21, 2010 Presentation Title 14

15 Thyrotoxicosis and Minerals Serum and urinary calcium levels are mildly elevated. Urinary losses of phosphorus are even greater than calcium. Total body magnesium is low in spite of normal or high serum levels. Losses of potassium in the urine depend on the extent of protein catabolism. Mineral absorption from the gut can compensate for excretory losses if adequate amounts are in the diet. Hypercalcemia stimulates thyroid parafollicular cells to secrete calcitonin resulting in a lowering of the calcium concentration. May 21, 2010 Presentation Title 15

16 Copper and the Thyroid Gland Most plasma Cu (approximately 93%) is bound to ceruloplasmin and a small fraction to albumin (6 to 7%) or is chelated to amino acids (<1%), which is diffusible. Thyroid hormones enhance the synthesis of lysozymal enzymes in muscle and are necessary for the catabolic response and increase the concentration of free amino acids in plasma. A general increase in plasma amino acid concentrations in hyperthyroid rats has been reported, and an increased plasma ceruloplasmin level in patients with hyperthyroidism. May 21, 2010 Presentation Title 16

17 Environmental Factors Inadequate intakes of iodine, selenium, and zinc can also be exacerbated by environmental factors, because their concentrations in plant-based foods are dependent on soil trace element levels. May 21, 2010 Presentation Title 17

18 Hypothyroidism and Anemia In humans, a mild anemia is found in the majority of patients with thyroid deficiency. The anemia may be hypochromic, megaloblastic, normochromic, or normocytic. Hypothyroidism reduces iron and vitamin B12 absorption and at least some of the associated anemias can be corrected by the appropriate nutrient. May 21, 2010 Presentation Title 18

19 Iron and Iodine Iodine deficiency is also exacerbated by coexisting iron deficiency (Zimmermann et al. 2000). Subjects with iron deficiency anemia; Levels of plasma thyroxine (T4) and triiodothyronine (T3) are lower. Conversion of T4-T3 is slowed. Concentrations of TSH are elevated (Beard et al. 1998). May 21, 2010 Presentation Title 19

20 Iron and Thyroid The 2 initial steps of thyroid hormone synthesis are catalyzed by thyroperoxidases and are dependent on iron. Iodine incorporation into tyrosine residues of thyroglobulin and covalent bridging of the residues are catalyzed by heme-containing thyroperoxidases. Theoretically, severe iron deficiency could lower thyroperoxidase activity and interfere with thyroid hormone synthesis. Animal and human studies suggest that iron deficiency impairs thyroid metabolism. Iron deficiency anemia decreases plasma thyroxine (T4) and triiodothyronine (T3) concentrations, reduces peripheral conversion of T4 to T3, and may increase concentrations of thyrotropin. Compared with healthy control subjects, iron-deficient adults have lower circulating T4 and T3 concentrations and higher thyrotropin concentrations. May 21, 2010 Presentation Title 20

21 Hypothyroidism and Vitamin A Thyroid hormones facilitate the conversion of the carotenes of vitamin A. When thyroid insufficiency exists, hypercarotenemia may develop imparting the yellow discoloration to the skin of myxedematous patients. May 21, 2010 Presentation Title 21

22 Vitamin A and Iodine Coexisting suboptimal vitamin A status (<1.05 umol/1) can also exacerbate iodine deficiency. Mechanism (proposed) Involves inhibition of thyroid-stimulating hormone (TSH) secretion by the pituitary and thyroid hormone transport, mediated in part through retinol-binding protein and transthyretin. May 21, 2010 Presentation Title 22

23 Nutritional Relationships with Male Infertility May 21, 2010 Presentation Title 23

24 Zinc and Infertility Clinical studies with adult males experimentally deprived of zinc show that Leydig cell synthesis of testosterone is dependent on adequate dietary zinc. There is some evidence that zinc is required for normal functioning of the hypothalamic-pituitary-gonadal axis. There is considerable evidence that zinc deficiency causes primary testicular failure and altered testicular steroidogenesis. J Trace Elem Exp Med 1990 AJCN 1991:53: Nutr Res May 21, 2010 Presentation Title 24

25 Sperm Motility and Zinc Several studies have shown that oral zinc supplementation improves sperm motility in subfertile men with idiopathic asthenozoospermia and/or oligozoospermia. (Andrologia 1988) May 21, 2010 Presentation Title 25

26 Zinc and Its Role In Immunology Research indicates that the zinc and albumin secreted from the prostate form a complex that coats the sperm and thereby protects the cells. Prostatic zinc may have antibacterial activity because Trichomonas vaginalis is readily killed at concentrations of zinc that occur in the prostatic fluid of healthy men. Genitourin Med 1987:63 May 21, 2010 Presentation Title 26

27 Sperm Volume There are also several factors known to decrease semen volume. Compared with nonsmoking control subjects, persons who smoked > 16 cigarettes/d exhibited decreased seminal volumes. Nagy et al reported that, compared with nonalcoholic's of known fecundity, alcoholics exhibited decreased seminal volumes. Pathologies: Insulin-dependent diabetes mellitus (IDDM) Hyperprolactinemia Primary hypothyroidism Leukospermia Andrologia 1987, Alcohol Alcohol 1986, Diabetes Care 1989 and Andrologia 1985 May 21, 2010 Presentation Title 27

28 Calcium and Sperm Motility Calcium is thought to regulate the mitiation and maintenance of motility and calcium chelators stimulate sperm motility in ejaculated human semen. Motility and viability were also enhanced in semen samples containing less than the average concentration of ionized calcium compared with samples with higher Ca concentrations. Tash and Means found sperm motility to be inhibited by elevated intracellular calcium. Lancet 1984, Scand J Clin Lab Invest Suppl 1983, Biol Reprod 1982, Fertil Steril 1990 May 21, 2010 Presentation Title 28

29 DHA and Sperm Motility DHA is 22 carbons long and has 6 double bonds with the n 3 configuration. It is the most prominent fatty acid in the brain, retina, and spermatozoa and is necessary for vision, cognition, and sperm motility. AJCN-4/2007 May 21, 2010 Presentation Title 29

30 CoQ10 and Infertility Coenzyme Q10 [(CoQ10) also commonly called ubiquinone] is present in well-measurable levels in human seminal fluid, where it probably exerts important metabolic and antioxidant functions; seminal CoQ10 concentrations show a direct correlation with seminal parameters (count and motility). Alterations of CoQ10 content were also shown in conditions associated with male infertility, such as asthenozoospermia and varicocele (VAR). J Endocrinol Invest 2009 J Urol May 21, 2010 Presentation Title 30

31 Carnitine and Infertility L-carnitine and acetyl-l-carnitine has a supplementary effect in the treatment of idiopathic asthenospermia and improves the semen quality of the patient. Zhonghua Nan Ke Xue Feb Oxid Med Cell Longev Apr Asia Pac J Clin Nutr May 21, 2010 Presentation Title 31

32 Selenium and lnfertility 468 infertile men with idiopathic oligoasthenoteratospermia who were randomized to receive 200 mcg selenium orally daily (selenium group of 116), 600 mg N-acetyl-cysteine orally daily CONCLUSIONS: These results indicate that supplemental selenium and N-acetyl-cysteine improve semen quality. J Urol. 2/2009 May 21, 2010 Presentation Title 32

33 Antioxidants and Infertility The treatment of an inflammatory process by the synergic action of immune modulators and anti-oxidants could protect sperm during maturation and migration, leading to improved sperm function. Asian J Androl Mar May 21, 2010 Presentation Title 33

34 Nutrients Associated with Diabetes Mellitus May 21, 2010 Presentation Title 34

35 Diabetic Nephropathy ~ 80,000 individuals are diagnosed with renal failure per year in the US. Diabetes mellitus is the most common cause of kidney failure. Approximately 40%-50% of new cases per year. Approximately 21% of all patients with diabetes develop kidney disease. Approximately 100,000 people have kidney failure as a result of diabetes. Approximately 40% with Type 1 DM develop nephropathy and renal failure by the age of 50. Some develop prior to 30 years of age. NIDDM at least 5-20% have renal disease 20 years after diagnosis. 5/21/2010 May 21, 2010 Presentation Title 35

36 THIAMIN May prevent and decrease neuropathy. May decrease acute DM nephropathy. Diabetologia 2009 Diabetes Required for the synthesis of acetylcholine. Pyruvate dehydrogenase (B1 dependent enzyme). Synergistic with magnesium. Requirement increases with CHO intake. 5/21/2010 May 21, 2010 Presentation Title 36

37 ZINC Alters fat and carbohydrate metabolism. Diabetics tend to hyperexcrete zinc. Important in wound healing. May protect beta-cells. 5/21/2010 May 21, 2010 Presentation Title 37

38 COENZYME Q10 Lipid-soluble molecule derived mainly from endogenous synthesis. Can lower BP ( mg/d) Higher serum CoQ levels have been associated with lower HbA1c. Has not been found to improve FBG or insulin concentrations. Found to be low in diabetics May prevent nephropathy May prevent & decrease neuropathy Antioxidant May reduce oxidative stress by inhibiting the generation of superoxide by mitochondria. (controversial) May 21, 2010 Presentation Title 38

39 Statins and CoQ10 CoQ10-lowering effect of statins and its compensation by administration of CoQ10 was described approximately 15 y ago and since then has been confirmed in numerous studies of animals and humans. AJCN (1/2000) Long-term statin treatment may be associated with chronic peripheral neuropathy. Eur J Clin Pharmacol Jan;54(11):835-8 Adverse reactions myalgia; myopathies; rhabdomyolysis; gastrointestinal symptoms, including hepatic injury; and the initiation or accelerated progression of cataracts and neoplasia could be a direct or indirect consequence of the CoQ10-deficiency state associated with statin treatment. AJCN (1/2000) 5/21/2010 May 21, 2010 Presentation Title 39

40 Case Study #1 71 year-old male Dx. Hypothyroidism, HTN & Hyperlipidemia SpectraCell results (11/2007) Vitamin B12 Pantothenate Vitamin D Zinc Glutathione Spectrox - 52% May 21, 2010 Presentation Title 40

41 Case Study #2 34 year-old female Dx: Crohn s disease, Hypothyroidism and Fatigue SpectraCell results (10/2008) Asparagine Vitamin D Selenium Vitamin E Glucose/Insulin Interaction Spectrox: 38.0% May 21, 2010 Presentation Title 41

42 Please join us next month, Thursday June 17 th, for our webinar on, Nutritional Considerations of Sports Medicine. To register log on to May 21, 2010 Presentation Title 42

Nutritional Considerations of Endocrinology Part 1: Women s Health. Presented by Dr. Ron Grabowski, R.D., D.C.

Nutritional Considerations of Endocrinology Part 1: Women s Health Presented by Dr. Ron Grabowski, R.D., D.C. April 19, 2010 Thyroid Gland and Nutritional Considerations April 19, 2010 Subclinical Hypothyroidism