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نقش ويتامين D در سلامت. فروزان صالحي دفتر بهبود تغذيه جامعه شهريور 1393. ویتامین D. محلول در چربی Sunshine vitamin هورمون یا ماده مغذی؟ پیش سازهای ویتامین :D (7-دهیدرو کلسترول و ارگوسترول). ویتامین D. انواع : ويتامين D 2 (گياهي: ارگوكلسيفرول)
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نقش ويتامين D در سلامت فروزان صالحي دفتر بهبود تغذيه جامعه شهريور 1393
ویتامین D • محلول در چربی • Sunshine vitamin • هورمون یا ماده مغذی؟ • پیش سازهای ویتامین :D (7-دهیدرو کلسترول و ارگوسترول)
ویتامین D • انواع: • ويتامين D2 (گياهي: ارگوكلسيفرول) • ويتامين D3 (جانوري: كولهكلسيفرول) • وظيفه اصلی: • اهميت در تنظيم غلظت كلسيم، فسفر و متابوليسم استخواني • ساير وظايف: • اثرات ضد سرطاني (در سلولهاي خوني، پستان، ريه، رحم و كولون) • تمايز سلولي در برخي بافتها
منابع • نور آفتاب • 90 درصد نياز از تابش مستقيم نور خورشيد فراهم ميشود • بهترين ساعت روز: 10 تا 15 • بهترين: فصل تابستان • بهترين عرض جغرافيايي: استوا • دستها، بازوها؛صورت، گردن و پاها: به ميزان نصف تا ثلث زماني كه پوست ميسوزد! • حداقل 2 بار در هفته (3 تا 4 بار ) • بهترین طول موج 300-270
منابع غذایی • روغن جگر ماهی • ماهی های چرب (شاه ماهی herring، خالمخالی mackerel و آزاد salmon) • زردۀ تخم مرغ • کره • جگر • شیر و لبنیات • سفرۀ غذایی ایران به طور معمول از نظر ویتامین D فقیر است!
3 oz smoked salmon = 583 IU 3 oz light tuna, canned in oil = 229 IU 1 large, whole egg = 29 IU
دریافت های غذایی مرجع (DRIs) • µg0/025= IU 1 • در شیرخوارگی و کودکی: µg5 • دریافت کافی (AI) برای بزرگسالان 51 سال به بالا: µg 10 (IU400) • برای 71 سال به بالا µg 15 (IU600) • حد قابل تحمل (UL): شیرخواران µg 25 (IU1000)؛ بزرگسالان µg 50 (IU2000) در روز
Adequate daily intake of Vit D The recommendation adequate intakes for vitamin D are inadequate, and, in the absence of exposure to sunlight, a minimum of 1000IU vitamin D is required to maintain a health concentration of 25(OH)D in the blood. -Holick MF
روشهای ارزیابی وضع تغذیۀ ویتامین D • اندازه گیری سطح سرمی 1, 25(OH)2D؟؟ • اندازه گیری سطح سرمی 25(OH)D • RIAو HPLC • Bone alkaline phosphatase (BALP) • استئوکلسین • کلسیم تام و یونیزه، فسفات
یک میلیارد نفر در دنیا دچار کمبود ویتامین د یا ویتامین د ناکافی (در حاشیه کمبود) هستند • در امریکا و اروپا 40 تا 100 درصد افراد مسن در جامعه دچار کمبود ویتامین د هستند • حتی در آفتابی ترین مناطق دنیاکمبود ویتامین د شایع است در کشورهای آفتابی مثل عربستان سعودی، امارات، استرالیا ، ترکیه، هندوستان و لبنان 30 تا 50 درصد بچه ها و بزرگسالان کمبود ویتامین د داشتند
افراد درمعرض کمبود ویتامین D • افرادی که مدت طولانی به دور از نور خورشید هستند • ساکنان مناطق با عرض جغرافیایی شمالی • ساکنان مناطق با آلودگی سنگین هوا • افراد با لباس های کاملاً پوشیده • افراد شب کار • افراد با پوست تیره • سالمندان • کودکان شیرخوار • استفاده ار کرم های ضد آفتاب با SPFبالای 8
عوارض کمبود ویتامینD • ریکتز (در کودکان) • استئومالاسی (در بزرگسالان) • استئوپروز؟ در كنار كاهش فعاليت بدني، قطع هورمونهاي جنسي و دريافت ناكافي كلسيم)
ریکتز • کمبود ویتامین D • نقص در تولید 25(OH)D3 • افزایش متابولیسم 25(OH)D3 • نقص در تولید 1,25(OH)2D3 • مقاومت به 1,25(OH)2D3
ریکتز • عوامل جغرافیایی • عوامل فرهنگی • عوامل اجتماعی • وضع تغذیۀ مادر باردار • فقر شیر مادر از نظر ویتامین D • رنگ پوست
ویتامین D و سرطان • تاثیر بر روی شیوع سرطان و مرگ ناشی از آن • مکانیسم اثر: • کاهش رشد سلول های سرطانی • افزایش تمایز سلولی • تحریک مرگ سلولی دستگاه گوارش، پروستات، پستان، لنفوم، آندومتر و ریه
June, 2007 American Journal of Clinical Nutrition • Women who regularly took vitamin D3 and calcium had a 60% reduction in all-cancer incidence compared with a group taking placebo and a 77% reduction when the analysis was confined to cancers diagnosed after the first 12 months.
Vitamin D & Colon Cancer Research • Third National Health and Nutrition Examination Survey • Epidemiologic study • 16,818 participants • Examined blood levels of vitamin D • Results • Blood levels 80nmol/L or higher reduced risk by 72%
Lung cancer 1,25(OH)2D: • inhibits proliferation and induces differentiation of lung cancer cell lines (Higashimoto, et al., 1996, Guzey, et al., 1998) • inhibits metastatic growth and locoregional recurrence of lung cancer cells in mice (Wiers, et al., 2000)
Lung cancer • 456 patients with early stage NSCLC • Median age – 69 • 96% Caucasian • Data collection: • Season of surgery • Food frequency questionnaire • Recurrence free survival (RFS) • Overall survival (OS) Zhou, et al., 2005
Breast cancer 1,25(OH)2D: • inhibits cell proliferation, induces differentiation & apoptosis, and inhibits angiogenesis in normal and breast cancer cells (Colston, et al, 1989, Saez, et al, 1993, Mantell, et al., 2000) • suppresses high-fat diet-induced mammary tumorigenesis in rats (Jacobson, et al., 1989, Xue, 1999)
Breast cancer • Inverse association between vitamin D & calcium intake and breast density • Inconclusive results in studies looking at VDR genetic polymorphisms and breast cancer • Inverse association between high sunlight exposure and breast cancer risk • Association may be stronger for premenopausal than postmenopausal women due to interactions between vitamin D, the VDR, estrogen and insulin-like growth factor-I (IGF-I) Cui & Rohan, 2006
Breast cancer • Case-control study – 972 women with newly-diagnosed breast cancer & 1,135 healthy controls • Interviews regarding vitamin D-related exposures, e.g. outdoor activities, use of sunscreen, dietary contributions Knight, 2007
Breast cancer • More frequent sun exposure during adolescence was associated with a 35% reduction in breast cancer risk later in life • Lower risk also linked to cod liver oil and milk intake > 10 glasses / week • Milder protection seen for people age 20 – 29 • No protection for people over age 45
Breast cancer • Epidemiologic study of different regions of Norway, each with a different annual UV exposure • Prognosis 15 – 25% better for women diagnosed / treated in the summer vs. winter <get this article: Breast Cancer Research and Treatment, May>Knight , 2007
Endometrial cancer Is ultraviolet B irradiance inversely associated with incidence rates of endometrial cancer: an ecological study of 107 countries. Mohr, et al, 2007
Endometrial cancer • Objective: perform an ecological analysis of the relationship between low levels of ultraviolet B irradiance and age-standardized incidence rates of endometrial cancer by country, controlling for known confounders
Endometrial cancer • 107 countries: • UVB irradiance • cloud cover • intake of energy from animal sources • proportion overweight • skin pigmentation • cigarette consumption • health expenditure • total fertility rates • vs. age-standardized incidence of endometrial cancer
Endometrial cancer • Association found between endometrial cancer incidence rates and: • Low UVB irradiance • High intake of energy from animal sources ( IGF-I?) • Per capital health expenditure • Proportion of population overweight
Pancreatic cancer • Prospectively collected diet and lifestyle data • Nurses’ Health Study – 75,427 women • Health Professionals Follow-up Study – 46,771 men • Pancreatic cancer risk 41% lower among those who consumed > 600 IU of vitamin D / day vs. those who consumed < 150 IU / day Skinner, et al., 2006
Multiple Sclerosis, Vitamin D U.S. nurses taking the most vitamin D had a relative risk of MS of 0.66 vs. least vitamin D Fish consumption also reduces the risk of MS. Fish is a good source of vitamin D.
Multiple Sclerosis: Prevention by Vitamin D Itestimate that 40-70% of MS in the U.S. could have been prevented through adequate vitamin D, especially in winter This is the season when infectious diseases are most common; MS appears to be caused by infectious disease Circulating vitamin D levels are lowest in winter
Other Diseases that UVB/Vitamin D Helps Prevent Muscle pain, weakness Progression of rheumatoid and osteo-arthritis Type 1 diabetes mellitus in infancy Type 2 diabetes mellitus Body, brain disorders during fetal development Irritable bowel syndrome, Crohn’s disease High blood pressure, heart disease Tuberculosis
Associations of low vitamin D status with chronic disease Osteopathy Myopathy Infection Inflammatory and autoimmune disease Hypertension, cardiovascular disease and diabetes mellitus Cancer
Type 2 Diabetes • Altered vitamin D and calcium homeostasis may play a role in development of type 2 diabetes • Low serum levels of 25(OH)D are associated with impaired pancreatic β cell function and insulin resistance • High calcium intake is inversely associated with body weight
Type 2 Diabetes • Nurses’ Health Study – 83,779 women (98% Caucasian) • Daily intake of >1,200 mg calcium & >800IU vitamin D was associated with a 33% lower risk of type 2 diabetes compared with an intake of <600 mg calcium & <400 IU vitamin D Pittas, et al., 2006
Type 1 Diabetes • Birth-cohort study in Finland – all women due to give birth in 1966 enrolled • 10,366 children born alive and followed to one year; 81 diagnosed with Type 1 diabetes • Children who regularly took recommended dose of vitamin D (2000 IU) had a RR of 0.22 compared with those who did not. • Children suspected of having rickets had a RR of 3.0 compared with those not suspected. Hopponen, et al., 2001
Metabolic Syndrome • Third National Health & Nutrition Examination Survey (NHANES III) • 8,421 men and non-pregnant women > 20 years of age and had fasted > 8 hrs • Unadjusted prevalence of metabolic syndrome - 21.9%
Metabolic Syndrome • After adjustments for known risk factors, odd of metabolic syndrome decreased progressively across increasing concentrations of 25(OH)D • Relative risk compared with bottom quintile of vitamin D level: • 2nd quintile – 0.85 • 3rd quintile – 0.75 • 4th quintile – 0.62 • 5th quintile – 0.46 Ford, et al., 2005
Pulmonary / COPD • Third National Health & Nutrition Examination Survey (NHANES III) • 14,000 subjects • Dose-response correlation between percent predicted FEV1 and FVC values and circulating 25(OH)D • Plausibility: vitamin D shown to prevent experimental inflammatory diseases in mice including allergic asthma Black, et al., Chest, 2005
Congestive Heart Failure • RCT of vitamin D + calcium vs. placebo + calcium x 9 months in subjects with CHF • 93 subjects completed study • Anti-inflammatory cytokine interleukin 10 significantly higher • Suppressed release of TNF-α • No difference in survival but blood levels not optimized Schleithoff, et al., 2006