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

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

2 Thyroid Gland and Nutritional Considerations April 19, 2010

3 Subclinical Hypothyroidism Defined as an elevated serum thyroidstimulating hormone (TSH) level with normal free thyroid hormone values. The prevalence of subclinical hypothyroidism is 4 to 8 percent in the general population, and up to 15 to 18 percent in women who are older than 60 years. April 19, 2010 Nutritional Considerations of Endocrinology 3

4 Thyroid Gland Synthesizes two major hormones Triiodothyronine (T3) main biologically active thyroid hormone Thyroxine (T4) precursor of T3 The synthesis of T4 and T3 occurs within thyroglobulin at the cell-colloid interphase. April 19, 2010 Nutritional Considerations of Endocrinology 4

5 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. April 19, 2010 Nutritional Considerations of Endocrinology 5

6 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. Deiodinase type II plays an important role in providing intracellular T3 to the brain and pituitary. Type III deiodinase catalyzes the conversion of T4 to biologically inactive reverse T3 and catabolizes T3 to produce inactive 3,3'- diiodothyronine. Selenium also plays a role in oxidative stress control at the thyroid as a component of the enzyme glutathione peroxidase. April 19, 2010 Nutritional Considerations of Endocrinology 6

7 Glutathione Peroxidase The selenoenzymes, glutathione peroxidase and thioredoxin reductase, are crucial to the protection of the thyroid from the hydrogen peroxide that is produced there to oxidize iodide for thyroid hormone synthesis. J Endocrinol 2005 & Br Med Bull 1999 An inverse association was found between selenium status and thyroid volume, thyroid tissue damage, and goiter in French women and with the positive association between the incidence of thyroid cancer and low prediagnostic serum selenium concentration in Norway. Eur J Endocrinol 2003, Int J Epidemiol 1989 & Sci Total Environ April 19, 2010 Nutritional Considerations of Endocrinology 7

8 Histologic Evaluations Thyroid glands of selenium-deficient animals showed an active fibrotic process in which the inflammatory reaction and excess of transforming growth factor-b 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 Selenium. April 19, 2010 Nutritional Considerations of Endocrinology 8

9 Selenium Dosage Protective effects of selenium on the thyroid are confirmed by the finding that supplementation with 200 µg/d of sodium selenite or selenomethionine decreased inflammation and thyroid autoantibody concentrations in patients with autoimmune thyroiditis. Biofactors-2003, Eur J Endocrin-2003 & J Endocrinol-2006 Important note: A dose of 100 µg selenomethionine/d was ineffective. April 19, 2010 Nutritional Considerations of Endocrinology 9

10 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. April 19, 2010 Nutritional Considerations of Endocrinology 10

11 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). April 19, 2010 Nutritional Considerations of Endocrinology 11

12 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. April 19, 2010 Nutritional Considerations of Endocrinology 12

13 Leukonychia April 19, 2010 Nutritional Considerations of Endocrinology 13

14 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. April 19, 2010 Nutritional Considerations of Endocrinology 14

15 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. April 19, 2010 Nutritional Considerations of Endocrinology 15

16 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 anemia's can be corrected by the appropriate nutrient. April 19, 2010 Nutritional Considerations of Endocrinology 16

17 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). April 19, 2010 Nutritional Considerations of Endocrinology 17

18 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. April 19, 2010 Nutritional Considerations of Endocrinology 18

19 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. April 19, 2010 Nutritional Considerations of Endocrinology 19

20 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. April 19, 2010 Nutritional Considerations of Endocrinology 20

21 Postpartum Depression Prevalence of antenatal depression can be as high as 20%, while approximately 12% to 16% of women experience postpartum depression. These are probably conservative estimates, as cases of maternal depression are underreported or under diagnosed. Risk factors for depression include genetic predisposition and environmental factors, as well as a number of social, psychological, and biological factors. Credible links between nutrient deficiency and mood have been reported for folate, vitamin B-12, calcium, iron, selenium, zinc, and n-3 fatty acids. For maternal depression, the nutrient that has received the most attention from nutrition researchers has been the n-3 essential fatty acids. J Am Diet Assoc. 9/2009 April 19, 2010 Nutritional Considerations of Endocrinology 21

22 Depression Major depressive disorder is very common, with a lifetime prevalence of 17% and a rate almost twice as high in women as in men. 22 Treatment Success: Between 19% and 34% of depressed patients still do not respond to acute antidepressant treatment % may fail to achieve and sustain a full remission. Between 15% and 50% will have a recurrence of depression despite continuous antidepressant treatment. April 19, 2010 Nutritional Considerations of Endocrinology 22

23 Postpartum Depression and Iron Deficiency Anemia Women in the United States who were enrolled in the Women, Infants, and Children (WIC) program, postpartum anemia occurred in 27% overall and in 48% of non-hispanic blacks. The risk of postpartum anemia was greatest in those who were anemic in pregnancy; 49% of women who were anemic in trimester 3 developed anemia postpartum compared with 21% who were nonanemic. Am J Obstet Gynecol 2001 Anemia postpartum is associated with increased risk of postpartum depression. J Nutr 2003 April 19, 2010 Nutritional Considerations of Endocrinology 23

24 Iron Deficiency 24 Final step of heme synthesis involves insertion of ferrous iron into protoporphyrin IX to form heme. April 19, 2010 Nutritional Considerations of Endocrinology 24

25 Pyridoxine Deficiency 25 First step in heme synthesis is catalyzed by aminolevulinic acid synthase. Vitamin B6-requiring enzyme. April 19, 2010 Nutritional Considerations of Endocrinology 25

26 Zinc Deficiency 26 Second step of heme synthesis is catalyzed by aminolevulinic acid dehydratase. Zinc metalloenzyme April 19, 2010 Nutritional Considerations of Endocrinology 26

27 Serotonin and Dopamine Zinc is important for the production and modulation of melatonin, which regulates dopamine function, and for the conversion of dietary pyridoxine to its active form, pyridoxal phosphate, which is necessary for the conversion of tryptophan to serotonin. Int J Neurosci-1990, Biol Trace Elem Res-1999, J Child Adolesc Psychopharmacol-2005 & Prog Neuropsychopharmacol Biol Psychiatry April 19, 2010 Nutritional Considerations of Endocrinology 27

28 NMDA Receptors One suggested pathway for depression is through zinc's effects on neurotransmitter responses at the NMDA (N-methyl-D-aspartate) receptors. Brain Res Bull-2001, Neurobiol Dis 1997 & Pol J Pharmacol-2003 Studies have suggested that NMDA glutamate receptors in depressed patients may be supersensitive, with dysregulation of glutamate often described in depression. Neuropharmacol April 19, 2010 Nutritional Considerations of Endocrinology 28

29 Glutamate The major neurotransmitter in excitatory hippocampal pathways, may over stimulate the NMDA pathway in sensitive individuals, leading to aberrant brain biochemical activity or brain cell atrophy and loss associated with depression. J Nutr-2000, Neuroscience-2000, J Histochem Cytochem 1990, Mol Psychiatry-1996 April 19, 2010 Nutritional Considerations of Endocrinology 29

30 Adenosine Receptors and Zinc Zinc may exhibit an antidepressant effect through direct or indirect activation of adenosine A 1 and A 2A receptors or a possible up-regulation of neuroprotective effectors (eg, glutathione). Biol Psychiatry-2008 & Behav Brain res April 19, 2010 Nutritional Considerations of Endocrinology 30

31 Albumin and Zinc An Italian study noted a relation between the concentration of albumin (as an indicator of zinc status) and depression 71% of participants with an albumin deficiency had a higher score on a measure of depression than did the 29% of participants with a normal albumin value. Rejuvenation Res April 19, 2010 Nutritional Considerations of Endocrinology 31

32 Depression & B-Vitamins 32 Low blood folate and cobalamin (vitamin B-12) concentrations have been found in patients with major depression in a number of studies. Psychosomatics 1980 J Affect Disord 1990 Psychiatr Prax 1995 Acta Psychiatr Scand 1989 Low blood folate concentrations have been associated with a poor response to antidepressant treatment, and in some studies there has been an inverse correlation between blood folate concentrations and the severity of depression. Psychiatry Res 1994 Am J Psychiatry 1997 April 19, 2010 Nutritional Considerations of Endocrinology 32

33 Vitamin D Deficiency Osteopenia/Osteoporosis Diabetes mellitus and Syndrome X Increased risk of common cancers Autoimmune diseases (RA, MS, Crohn s disease) Hypertension Infectious diseases Depression (J Nutr Health Aging 1999) April 19, 2010 Nutritional Considerations of Endocrinology 33

34 Zinc Consumption According to the US Department of Agriculture, 50% of persons who follow the Dietary Guidelines for Americans (DGA) have zinc intakes that are 75% of the RDA. April 19, 2010 Nutritional Considerations of Endocrinology 34

35 Zinc and Diabetes Mellitus Insulin synthesis Insulin secretion J Am Coll Nutr 1998 April 19, 2010 Nutritional Considerations of Endocrinology 35

36 Vitamin D and Diabetes Mellitus Vitamin D deficiency inhibits pancreatic secretion of insulin and 1,25(OH) 2 D 3 restores it. Diabetes 1985, Science 1980 Vitamin D deficiency in early life accelerates development of type 1 diabetes in nonobese diabetic mice. Diabetologia 2004, Trends Endocrinol Metab 2005 In humans, 25(OH)D concentration has a positive correlation with insulin sensitivity and hypovitaminosis D has a negative effect on β cell function. April 19, 2010 Nutritional Considerations of Endocrinology 36

37 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): 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) April 19, 2010 Nutritional Considerations of Endocrinology 37

38 Metformin (Glucophage) Vitamin B12 deficiency Chronic metformin use results in vitamin B12 deficiency in 30% of patients. South Med J J Am Board Fam Med Diabetes Care April 19, 2010 Nutritional Considerations of Endocrinology 38

39 Case Study #1 62 year old female CC: Breast carcinoma metastasis (remission for 13 years) Past Medical Hx: Hypothyroidism, Anemia and Osteoporosis SpectraCell results (3/2009) Deficiencies: Asparagine, Chromium, Zinc, Glutathione and Glucose/Insulin Interaction Marginal: Riboflavin, Calcium and Cysteine April 19, 2010 Nutritional Considerations of Endocrinology 39

40 Case Study #2 71 year-old male Dx. Hypothyroidism, HTN & Hyperlipidemia SpectraCell results (11/2007) Vitamin B12 Pantothenate Vitamin D Zinc Glutathione Spectrox - 52% April 19, 2010 Nutritional Considerations of Endocrinology 40

41 Case Study #3 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% April 19, 2010 Nutritional Considerations of Endocrinology 41

42 Please join us next month, Thursday May 20 th, for our webinar on, Nutritional Considerations of Endocrinology Part 2: Men s Health. To register log on to April 19, 2010 Nutritional Considerations of Endocrinology 42

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

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