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Abstracts

Life Extension Magazine October 2011
Abstracts

Iodine

Iodine-deficiency prophylaxis and the restriction of salt consumption - a 21st century challenge.

The World Health Organization (WHO) issued a recommendation (Technical Consultation: Paris 2006, Luxembourg 2007) that salt consumption, as a risk factor for hypertension, atherosclerosis, myocardial infarction, stroke, and select cancers, should be restricted. The European Commission looked to adhere to this recommendation by creating the High Level Group on Nutrition and Physical Activity. According to WHO recommendations, a daily allowance of 5 g NaCl (i.e., 2 g Na) for individual salt consumption should not be exceeded. At present, mean individual salt consumption in Poland totals 13.5 g, of which salt used in household constitutes 8.8 g. In some regions of Poland, this number reaches upwards of 15.0 g/person. The Position Paper on Initiatives Aimed at Decreasing Salt Consumption in Poland, developed by an expert group at the National Food and Nutrition Institute, set the course for intervention, including changing recipes for massproduced food products and large-scale catering, improving oversight by food control agencies, and continuing legislative changes. These interventions should also include education directed towards consumers, food producers, public health professionals, healthcare workers, and media representatives. The Position Paper of the Polish Hypertension Society also sets the course for promoting restricted salt consumption and controlling hypertension on a population level. However, household salt is the main carrier of iodine in the Polish model of iodine prophylaxis. Thus, any interventions also require synchronized action with the Polish Council for Control of Iodine Deficiency Disorders. Current efforts aimed at preventing iodine-deficiency look to increase consumption of other iodine-rich products (e.g., milk, mineral water) with standardized levels of iodine. Once they achieve an iodine concentration of 0.1-0.2 mg, these products can easily supplement any decrease in physiological iodine levels resulting from reduced salt consumption. Also required are wide-ranging educational campaigns which will be coordinated by the new designated WHO Collaborating Centre for Nutrition at the Chair of Endocrinology at Jagiellonian University, Collegium Medicum in Kraków.

Endokrynol Pol. 2010 Jan-Feb;61(1):135-40

Iodine deficiency.

Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected. However, about 50% of Europe remains mildly iodine deficient, and iodine intakes in other industrialized countries, including the United States and Australia, have fallen in recent years. Iodine deficiency during pregnancy and infancy may impair growth and neurodevelopment of the offspring and increase infant mortality. Deficiency during childhood reduces somatic growth and cognitive and motor function. Assessment methods include urinary iodine concentration, goiter, newborn TSH, and blood thyroglobulin. But assessment of iodine status in pregnancy is difficult, and it remains unclear whether iodine intakes are sufficient in this group, leading to calls for iodine supplementation during pregnancy in several industrialized countries. In most countries, the best strategy to control iodine deficiency in populations is carefully monitored universal salt iodization, one of the most cost-effective ways to contribute to economic and social development. Achieving optimal iodine intakes from iodized salt (in the range of 150-250 microg/d for adults) may minimize the amount of thyroid dysfunction in populations. Ensuring adequate iodine status during parenteral nutrition has become important, particularly in preterm infants, as the use of povidone-iodine disinfectants has declined. Introduction of iodized salt to regions of chronic iodine deficiency may transiently increase the incidence of thyroid disorders, but overall, the relatively small risks of iodine excess are far outweighed by the substantial risks of iodine deficiency.

Endocr Rev. 2009 Jun;30(4):376-408

Role of iodine, selenium and other micronutrients in thyroid function and disorders.

Micronutrients, mostly iodine and selenium, are required for thyroid hormone synthesis and function. Iodine is an essential component of thyroid hormones and its deficiency is considered as the most common cause of preventable brain damage in the world. Nowadays about 800 million people are affected by iodine deficiency disorders that include goiter, hypothyroidism, mental retardation, and a wide spectrum of other growth and developmental abnormalities. Iodine supplementation, under form of iodized salt and iodized vegetable oil, produced dramatic improvements in many areas, even though iodine deficiency is still a problem not only for developing countries. In fact, certain subpopulations like vegetarians may not reach an adequate iodine intake even in countries considered iodine-sufficient. A reduction in dietary iodine content could also be related to increased adherence to dietary recommendations to reduce salt intake for preventing hypertension. Furthermore, iodine intakes are declining in many countries where, after endemic goiter eradication, the lack of monitoring of iodine nutrition can lead to a reappearance of goiter and other iodine deficiency disorders. Three different selenium-dependent iodothyronine deiodinases (types I, II, and III) can both activate and inactivate thyroid hormones, making selenium an essential micronutrient for normal development, growth, and metabolism. Furthermore, selenium is found as selenocysteine in the catalytic center of enzymes protecting the thyroid from free radicals damage. In this way, selenium deficiency can exacerbate the effects of iodine deficiency and the same is true for vitamin A or iron deficiency. Substances introduced with food, such as thiocyanate and isoflavones or certain herbal preparations, can interfere with micronutrients and influence thyroid function. Aim of this paper is to review the role of micronutrients in thyroid function and diseases.

Endocr Metab Immune Disord Drug Targets. 2009 Sep;9(3):277-94

Projected effect of dietary salt reductions on future cardiovascular disease.

BACKGROUND: The U.S. diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is a potentially important target for the improvement of public health. METHODS: We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable, population-wide reductions in dietary salt of up to 3 g per day (1200 mg of sodium per day). We estimated the rates and costs of cardiovascular disease in subgroups defined by age, sex, and race; compared the effects of salt reduction with those of other interventions intended to reduce the risk of cardiovascular disease; and determined the cost-effectiveness of salt reduction as compared with the treatment of hypertension with medications. RESULTS: Reducing dietary salt by 3 g per day is projected to reduce the annual number of new cases of CHD by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial infarction by 54,000 to 99,000 and to reduce the annual number of deaths from any cause by 44,000 to 92,000. All segments of the population would benefit, with blacks benefiting

proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits of reduced salt intake are on par with the benefits of population-wide reductions in tobacco use, obesity, and cholesterol levels. A regulatory intervention designed to achieve a reduction in salt intake of 3 g per day would save 194,000 to 392,000 quality-adjusted life-years and $10 billion to $24 billion in health care costs annually. Such an intervention would be cost-saving even if only a modest reduction of 1 g per day were achieved gradually between 2010 and 2019 and would be more cost-effective than using medications to lower blood pressure in all persons with hypertension. CONCLUSIONS: Modest reductions in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target.

N Engl J Med. 2010 Feb 18;362(7):590-9

Urinary iodine concentration: United States National Health And Nutrition Examination Survey 2001-2002.

Urine iodine has been measured in the US population by the National Health and Nutrition Examination Survey (NHANES) since 1971. A downward trend was noted between NHANES I (320 +/- 6 microg/L in 1971-1974) and NHANES III (145 +/- 3 microg/L in 1988-1994). This report presents data from NHANES 2001-2002 that indicates that the U.S. median urine iodine (UI) level has stabilized since the initial drop between NHANES I and NHANES III. The median UI concentration in the U.S. population in NHANES 2001-2002 was found to be 167.8 microg/L (95% confidence interval [CI] 159.3-177.6). The NHANES 2001-2002 data confirm the current stability of the U.S. iodine intake and continued adequate iodine nutrition for the country.

Thyroid. 2005 Jul;15(7):692-9

Iodine deficiency in vegetarians and vegans.

Iodine content in food of plant origin is lower in comparison with that of animal origin due to a low iodine concentration in soil. Urinary iodine excretion was assessed in 15 vegans, 31 lacto- and lacto-ovovegetarians and 35 adults on a mixed diet. Iodine excretion was significantly lower in alternative nutrition groups - 172 microg/l in vegetarians and 78 microg/l in vegans compared to 216 microg/l in subjects on a mixed diet. One fourth of the vegetarians and 80% of the vegans suffer from iodine deficiency (iodine excretion value below 100 microg/l) compared to 9% in the persons on a mixed nutrition. The results show that under conditions of alternative nutrition, there is a higher prevalence of iodine deficiency, which might be a consequence of exclusive or prevailing consumption of food of plant origin, no intake of fish and other sea products, as well as reduced iodine intake in the form of sea salt.

Ann Nutr Metab. 2003;47(5):183-5

Iodine uptake and loss-can frequent strenuous exercise induce iodine deficiency?

Most of the daily dietary iodine intake (approximately 90%) will be excreted in the urine; measurement of urinary iodine excretion is thus routinely used as an index of dietary iodine intake. However, urinary excretion is not the only means of iodine loss. Subjects such as athletes or those participating in vigorous exercise can lose a considerable amount of iodine in sweat, depending on environmental factors such as temperature and humidity. In areas of lower to moderate dietary iodine intake, loss in sweat can equal that in urine. Although electrolyte loss in sweat is well-recognized and replacement strategies are adopted, there is less recognition of potential iodine loss. Crude calculations reveal that if sweat iodide losses are not replaced, dietary stores could be depleted in an athlete undergoing a regular training regime. The significance of these losses could be increased in areas where dietary iodine intake is lower in the summer months. Although there is little doubt that excessive sweating can induce a relative iodine deficiency state, there is no case as yet for iodine supplementation in those that take vigorous exercise. However, sustained iodine loss may have implications for thyroid status and possibly consequences for athletic performance.

Horm Metab Res. 2005 Sep;37(9):555-8.

Iodine: deficiency and therapeutic considerations.

Iodine deficiency is generally recognized as the most commonly preventable cause of mental retardation and the most common cause of endocrinopathy (goiter and primary hypothyroidism). Iodine deficiency becomes particularly critical in pregnancy due to the consequences for neurological damage during fetal development as well as during lactation. The safety of therapeutic doses of iodine above the established safe upper limit of 1 mg is evident in the lack of toxicity in the Japanese population that consumes 25 times the median intake of iodine consumption in the United States. Japan’s population suffers no demonstrable increased incidence of autoimmune thyroiditis or hypothyroidism. Studies using 3.0- to 6.0-mg doses to effectively treat fibrocystic breast disease may reveal an important role for iodine in maintaining normal breast tissue architecture and function. Iodine may also have important antioxidant functions in breast tissue and other tissues that concentrate iodine via the sodium iodide symporter.

Altern Med Rev. 2008 Jun;13(2):116-27

Iodine deficiency, more than cretinism and goiter.

Recent reports of the World Health Organization show iodine deficiency to be a worldwide occurring health problem. As iodine status is based on median urinary iodine excretion, even in countries regarded as iodine sufficient, a considerable part of the population may be iodine deficient. Iodine is a key element in the synthesis of thyroid hormones and as a consequence, severe iodine deficiency results in hypothyroidism, goiter, and cretinism with the well known biochemical alterations. However, it is also known that iodine deficiency may give rise to clinical symptoms of hypothyroidism without abnormality of thyroid hormone values. This led us to the hypothesis that iodine deficiency may give rise to subtle impairment of thyroid function leading to clinical syndromes resembling hypothyroidism or diseases that have been associated with the occurrence of hypothyroidism. We describe several clinical conditions possibly linked to iodine deficiency, a connection that has not been made thus far. In this paper we will focus on the relationship between iodine deficiency and obesity, attention deficit hyperactivity disorder (ADHD), psychiatric disorders, fibromyalgia, and malignancies.

Med Hypotheses. 2008 Nov;71(5):645-8

Tissue iodine content and serum-mediated 125I uptake-blocking activity in breast cancer.

In the thyroid, active transport of iodide is under control of the TSH-dependent Na+/I- symporter (NIS), whereas in the breast such control is less well understood. In this study, NIS expression was demonstrated by RT-PCR in 2 of 2 fibroadenomata and 6 of 7 breast carcinoma messenger ribonucleic acid isolates. In addition, mean total tissue iodine levels of 80.9 +/- 9.5 ng I/mg protein in 23 benign tumors (fibroadenomata) were significantly higher than those in 19 breast cancers taken from either the tumor (18.2 +/- 4.6 ng I/mg) or morphologically normal tissue taken from within the tumor-bearing breast (31.8 +/- 4.9 ng I/mg; P < 0.05 in each case). Inhibition of 125I uptake into NIS-transfected CHO cells was observed in serum from 20 of 105 (19.0%) breast carcinoma, 8 of 49 (16.3%) benign breast disease, and 27 of 86 (31.4%) Graves’ patients, but in only 1 of 33 (3.0%) age-matched female controls. IgG purified from serum of patients showing positive 125I uptake inhibition also

inhibited iodide uptake, suggesting that such inhibition was antibody mediated. 125I uptake inhibition was significantly associated with thyroid peroxidase antibody positivity (P < 0.05) in sera from breast cancer patients, but not in those with benign breast disease, once again suggesting an association between thyroid autoimmunity and breast carcinoma.

J Clin Endocrinol Metab. 2000 Mar;85(3):1245-50

Comparison of iodine contents in gastric cancer and surrounding normal tissues.

It has been suggested that iodine plays an important role in gastric cancer. Gastric cancer ranks first among the cancers in the north-eastern Anatolia region, Turkey, where iodine deficiency is common. In this study, iodine levels were determined in gastric cancer and surrounding normal tissues in 19 patients with gastric cancer. Tissue iodine levels were determined by the Foss method based on the Sandell-Kolt-hoff reaction. Tissue iodine levels were lower in gastric cancer tissue (17.8+/-3.4 ng I/mg protein, mean+/-SEM) compared with surrounding normal tissue (41.7+/-8.0 ng I/mg protein) (p<0.001). There was positive correlation between the iodine levels in gastric cancer tissue and surrounding normal tissue (r = 0.845, p<0.001). There was no significant difference in iodine levels in cancer and surrounding normal tissue between male and female subjects. The iodine deficiency in our region may be one of the factors for increased gastric cancer prevalence. Our results support the hypothesis that iodine plays an important role in gastric cancer development.

Clin Chem Lab Med. 2005;43(6):581-4

Iodine prophylaxis—the protective factor against stomach cancer in iodine deficient areas.

BACKGROUND: Poland has one of the highest death rates for stomach cancer in Europe. Moderate iodine deficiency and in consequence high goitre prevalence led to the implementation in 1996 of a very efficient mandatory model of iodine prophylaxis, based on household salt iodisation (30 +/- 10 mg KI/1 kg of salt). AIM OF THE STUDY: The aim of the study was evaluation of incidence rate of stomach cancer and its possible relation to increased iodine consumption in the years 1992-2004. METHODS: Iodine supply and effectiveness of iodine prophylaxis were evaluated on the basis of comparative analysis of goitre prevalence and ioduria in schoolchildren. To allow comparison between time periods with varying population age structures, the incidence rates of stomach cancer were standardized for age, using the “world standard population”. The direct standardization method has been applied. For each sex, the time-trend of incidence rates was shown in graphs over the years 1991-2004. RESULTS: Evident increase in iodine consumption in this period of time was proved by rise in percentage of schoolchildren (6-8 years old) with ioduria above 100 microg/l from 11.4% in 1992-1993 to 52.9.1% in 2003. It was correlated with the decrease in goitre prevalence from 18.8% to 3.2% respectively. The 24-h thyroid uptake of (131)I in investigated population fell from 45.5% in 1986 to 26.8% in 1998. In Krakow the standardized incidence ratio of stomach cancer for men decreased from 19.1 per 100,000 to 15.7 per 100,000, and for women from 8.3 per 100,000 to 5.9 per 100,000 in the years 1992-2004. A significant decline of average rate of decrease was observed in men and women (2.3% and 4.0% per year respectively). CONCLUSION: Observed association between improved iodine supply and decrease of incidence of stomach cancer could indicate the protective role against stomach cancer of iodine prophylaxis in iodine deficient areas--further studies are necessary.

Eur J Nutr. 2007 Aug;46(5):251-6

Iodide accumulation provides kelp with an inorganic antioxidant impacting atmospheric chemistry.

Brown algae of the Laminariales (kelps) are the strongest accumulators of iodine among living organisms. They represent a major pump in the global biogeochemical cycle of iodine and, in particular, the major source of iodocarbons in the coastal atmosphere. Nevertheless, the chemical state and biological significance of accumulated iodine have remained unknown to this date. Using x-ray absorption spectroscopy, we show that the accumulated form is iodide, which readily scavenges a variety of reactive oxygen species (ROS). We propose here that its biological role is that of an inorganic antioxidant, the first to be described in a living system. Upon oxidative stress, iodide is effluxed. On the thallus surface and in the apoplast, iodide detoxifies both aqueous oxidants and ozone, the latter resulting in the release of high levels of molecular iodine and the consequent formation of hygroscopic iodine oxides leading to particles, which are precursors to cloud condensation nuclei. In a complementary set of experiments using a heterologous system, iodide was found to effectively scavenge ROS in human blood cells.

Proc Natl Acad Sci U S A. 2008 May 13;105(19):6954-8