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Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status. Hollis BW, Wagner CL, Drezner MK, Binkley NC. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):631-4. Epub 2007 Jan 10. PMID: 17218096 In the present study, we sought to investigate what circulating 25(OH)D levels would result in populations exhibiting no substrate limitations to the vitamin D-25-hydroxylase. To perform this, we chose two distinct populations. The first were individuals from a year-found sunny environment who spent a good deal of time outdoors. The second were a group of lactating women receiving a substantial daily oral dose of vitamin D3. Surprisingly, a study such as this previously had not been undertaken. There are several reasons for this. First, finding a group of sun-exposed individuals is not an easy task; in fact, we had to go to Hawaii to find them. Secondly, very few studies have been performed where subjects actually received adequate vitamin D3 supplementation to make them replete. Finally, it is very difficult and costly to measure circulating vitamin D3 and relate it to circulating 25(OH)D. The results of our study are far-reaching. This study also demonstrates that individuals can be vitamin D deficient with significant sun exposure if the skin area exposed is limited as was suggested several years ago (19). Finally, whether one receives their vitamin D3 orally or through UV exposure, the vitamin D-25-hydroxylase appears to handle it in an equivalent fashion with respect to maintaining circulating 25(OH)D levels. Thus, we believe that the relationship between circulating vitamin D and 25(OH)D may define adequate nutritional vitamin D status.

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Using these functional indicators, several studies have more accurately defined vitamin D deficiency as circulating levels of 25(OH)D ≤ 80 nmol or 32 µg/L. Recent studies reveal that current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. Hollis BW. J Nutr. 2005 Feb;135(2):317-22. Review. PMID: 15671234 [

Alpha-linolenic acid and risk of nonfatal acute myocardial infarction. Campos H, Baylin A, Willett WC. Circulation. 2008 Jul 22;118(4):339-45. Epub 2008 Jul 7. Erratum in: Circulation. 2008 Sep 16;118(12):e492. PMID: 18606916 doi: 10.1161/CIRCULATIONAHA.107.762419 Conclusions - Consumption of vegetable oils rich in {alpha}-linolenic acid could confer important cardiovascular protection. The apparent protective effect of {alpha}-linolenic acid is most evident among subjects with low intakes.

Scientists have long known that a lack of vitamin D can weaken our bones. A new study shows that low levels of this nutrient may also be linked to a higher chance of dying early from heart and circulation problems, as well as other causes.

Dietary linolenic acid is inversely associated with calcified atherosclerotic plaque in the coronary arteries: the National Heart, Lung, and Blood Institute Family Heart Study. Djoussé L, Arnett DK, Carr JJ, Eckfeldt JH, Hopkins PN, Province MA, Ellison RC; Investigators of the NHLBI FHS. Circulation. 2005 Jun 7;111(22):2921-6. Epub 2005 May 31. PMID: 15927976 doi: 10.1161/CIRCULATIONAHA.104.489534

Vitamin D in preventive medicine: are we ignoring the evidence? Zittermann A. Br J Nutr. 2003 May;89(5):552-72. Review. PMID: 12720576 Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1alpha-hydroxylase into the vitamin D hormone calcitriol. Calcitriol receptors are present in more than thirty different tissues. Apart from the kidney, several tissues also possess the enzyme 1alpha-hydroxylase, which is able to use circulating 25(OH)D as a substrate. Serum levels of 25(OH)D are the best indicator to assess vitamin D deficiency, insufficiency, hypovitaminosis, adequacy, and toxicity. European children and young adults often have circulating 25(OH)D levels in the insufficiency range during wintertime. Elderly subjects have mean 25(OH)D levels in the insufficiency range throughout the year. In institutionalized subjects 25(OH)D levels are often in the deficiency range. There is now general agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Moreover, vitamin D insufficiency can lead to a disturbed muscle function. Epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer. Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites is able: (i) to reduce blood pressure in hypertensive patients; (ii) to improve blood glucose levels in diabetics; (iii) to improve symptoms of rheumatoid arthritis and multiple sclerosis. The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations of 5-15 microg/d.

Vitamin D deficiency and risk of cardiovascular disease. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D'Agostino RB, Wolf M, Vasan RS. Circulation. 2008 Jan 29;117(4):503-11. Epub 2008 Jan 7. PMID: 18180395 doi: 10.1161/CIRCULATIONAHA.107.706127 Conclusions- Vitamin D deficiency is associated with incident cardiovascular disease. Further clinical and experimental studies may be warranted to determine whether correction of vitamin D deficiency could contribute to the prevention of cardiovascular disease.

Matsuoka, L. Y., Wortsman, J., Hanifan, N. & Holick, M. F. (1988) Chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D: a preliminary study. Arch. Dermatol. 124:1802-1804

25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. Heaney RP, Armas LA, Shary JR, Bell NH, Binkley N, Hollis BW. Am J Clin Nutr. 2008 Jun;87(6):1738-42. PMID: 18541563 Conclusions: At physiologic inputs, there is rapid conversion of precursor to product at low vitamin D3 concentrations and a much slower rate of conversion at higher concentrations. These data suggest that, at typical vitamin D3 inputs and serum concentrations, there is very little native cholecalciferol in the body, and 25(OH)D constitutes the bulk of vitamin D reserves. However, at supraphysiologic inputs, large quantities of vitamin D3 are stored as the native compound, presumably in body fat, and are slowly released to be converted to 25(OH)D.

Effectiveness and safety of vitamin D in relation to bone health. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V. Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235. Review. PMID: 18088161 CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

Effectiveness and safety of vitamin D in relation to bone health. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V. Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235. Review. PMID: 18088161 CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

Egg consumption and risk of heart failure in the Physicians' Health Study. Djoussé L, Gaziano JM. Circulation. 2008 Jan 29;117(4):512-6. Epub 2008 Jan 14. PMID: 18195171 doi: 10.1161/CIRCULATIONAHA.107.734210 CONCLUSIONS: Our data suggest that infrequent egg consumption is not associated with the risk of HF. However, egg consumption of > or = 1 per day is related to an increased risk of HF among US male physicians.

In 1939, Dr. Abraham Myerson measured initial levels of circulating testosterone in men and exposed their various body parts to UVB light. After five days of chest exposure sufficient to cause reddening, circulating testosterone increased by 120%. After eight days without additional UV exposure, testosterone returned to initial levels. When the genital area was exposed, testosterone levels increased by 200%!

Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study. Salonen RM, Nyyssönen K, Kaikkonen J, Porkkala-Sarataho E, Voutilainen S, Rissanen TH, Tuomainen TP, Valkonen VP, Ristonmaa U, Lakka HM, Vanharanta M, Salonen JT, Poulsen HE; Antioxidant Supplementation in Atherosclerosis Prevention Study. Circulation. 2003 Feb 25;107(7):947-53. PMID: 12600905 doi: 10.1161/01.CIR.0000050626.25057.51 Conclusions- These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons.

Serum Long-Chain n-3 Polyunsaturated Fatty Acids and Risk of Hospital Diagnosis of Atrial Fibrillation in Men. Virtanen JK, Mursu J, Voutilainen S, Tuomainen TP. Circulation. 2009 Dec 8;120(23):2315-21. Epub 2009 Nov 23. PMID: 19933935 doi: 10.1161/CIRCULATIONAHA.109.852657 Conclusions- An increased concentration of long-chain n-3 PUFAs in serum, a marker of fish or fish oil consumption, may protect against AF. Serum docosahexaenoic acid concentration had the greatest impact

"Quality of HDL differs in diabetics but improves with niacin therapy December 22, 2009 | Michael O'Riordan Hannover, Germany - A small study published this week hints that the effects of HDL cholesterol differ in healthy patients from those with diabetes mellitus [1]. HDL cholesterol in individuals with diabetes has impaired endothelial protective functions compared with the HDL from healthy subjects, although treatment with extended-release niacin can improve these endothelial protective effects, according to researchers. Publishing their findings online December 21, 2009 in Circulation, lead investigator Dr Sajoscha Sorrentino (Hannover Medical School, Germany) and colleagues write that because recent HDL-raising intervention studies have yielded mixed results, "circulating HDL-cholesterol levels alone likely do not represent an adequate measure of therapeutic efficacy, and indexes of HDL functionality are urgently needed for assessment of the potential of HDL-targeted therapies to exert vasoprotective effects." Speaking with heartwire, senior investigator Dr Ulf Landmesser (University of Zürich, Switzerland), said the results have implications for clinical research. "We have to understand that we can't look only at the HDL levels in the plasma, but we need to look at the quality," he said. "The quality of the HDL is not the same in different patients. This is very important for targeting HDL as a treatment. Second, niacin therapy is a promising way not only to raise HDL but also to improve the quality; it is a good treatment option, especially if the larger outcomes data are positive.""

Fish intake and risk of incident atrial fibrillation. Mozaffarian D, Psaty BM, Rimm EB, Lemaitre RN, Burke GL, Lyles MF, Lefkowitz D, Siscovick DS. Circulation. 2004 Jul 27;110(4):368-73. Epub 2004 Jul 19. PMID: 15262826 doi: 10.1161/01.CIR.0000138154.00779.A5 Conclusions- Among elderly adults, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower incidence of AF. Fish intake may influence risk of this common cardiac arrhythmia.

Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Iso H, Kobayashi M, Ishihara J, Sasaki S, Okada K, Kita Y, Kokubo Y, Tsugane S; JPHC Study Group. Circulation. 2006 Jan 17;113(2):195-202. Epub 2006 Jan 9. PMID: 16401768 doi: 10.1161/CIRCULATIONAHA.105.581355 Conclusions- Compared with a modest fish intake of once a week or &20 g/d, a higher intake was associated with substantially reduced risk of coronary heart disease, primarily nonfatal cardiac events, among middle-aged persons

Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Leaf A, Kang JX, Xiao YF, Billman GE. Circulation. 2003 Jun 3;107(21):2646-52. Review. PMID: 12782616 doi: 10.1161/01.CIR.0000069566.78305.33 This review will be limited specifically to the beneficial prevention by the n-3 polyunsaturated fatty acids (PUFAs) of arrhythmic deaths, including sudden cardiac death, which annually causes some 300 000 deaths in the United States and millions more worldwide. We will also show that the growing body of positive clinical studies is supported by what has been learned in animal and laboratory studies regarding the mechanism by which n-3 PUFAs prevent cardiac arrhythmias.