Vitamin D deficiency is common in the elderly, especially in the housebound and in geriatric patients. The establishment of strict diagnostic criteria is hampered by differences in assay methods for 25-hydroxyvitamin D. The synthesis of vitamin D3 in the skin under influence of UV light decreases with aging due to insufficient sunlight exposure, and a decreased functional capacity of the skin. The diet contains a minor part of the vitamin D requirement. Vitamin D deficiency in the elderly is less common in the United States than elsewhere due to the fortification of milk and use of supplements. Deficiency in vitamin D causes secondary hyperparathyroidism, high bone turnover, bone loss, mineralization defects, and hip and other fractures. Less certain consequences include myopathy and falls. A diet low in calcium may cause an increased turnover of vitamin D metabolites and thereby aggravate vitamin D deficiency. Prevention is feasible by UV light exposure, food fortification, and supplements. Vitamin D3 supplementation causes a decrease of the serum PTH concentration, a decrease of bone turnover, and an increase of bone mineral density. Vitamin D3 and calcium may decrease the incidence of hip and other peripheral fractures in nursing home residents. Vitamin D3 is recommended in housebound elderly, and it may be cost-effective in hip fracture prevention in selected risk groups. (Endocrine Reviews 22: 477–501, 2001)

Vitamin D Deficiency and Secondary Hyperparathyroidism in the Elderly: Consequences for Bone Loss and Fractures and Therapeutic Implications

The relations between 24 hour urinary electrolyte excretion and blood pressure were studied in 10,079 men and women aged 20-59 sampled from 52 centres around the world based on a highly standardised protocol with central training of observers, a central laboratory, and extensive quality control. Relations between electrolyte excretion and blood pressure were studied in individual subjects within each centre and the results of these regression analyses pooled for all 52 centres. Relations between population median electrolyte values and population blood pressure values were also analysed across the 52 centres. Sodium excretion ranged from 0.2 mmol/24 h (Yanomamo Indians, Brazil) to 242 mmol/24 h (north China). In individual subjects (within centres) it was significantly related to blood pressure. Four centres found very low sodium excretion, low blood pressure, and little or no upward slope of blood pressure with age. Across the other 48 centres sodium was significantly related to the slope of blood pressure with age but not to median blood pressure or prevalence of high blood pressure. Potassium excretion was negatively correlated with blood pressure in individual subjects after adjustment for confounding variables. Across centres there was no consistent association. The relation of sodium to potassium ratio to blood pressure followed a pattern similar to that of sodium. Body mass index and heavy alcohol intake had strong, significant independent relations with blood pressure in individual subjects.

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Intersalt: An international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion

Objectives To review and synthesize the literature in the following areas: the association of specific circulating 25(OH)D concentrations with bone health outcomes in children, women of reproductive age, postmenopausal women and elderly men; the effect of dietary intakes (foods fortified with vitamin D and/or vitamin D supplementation) and sun exposure on serum 25(OH)D; the effect of vitamin D on bone mineral density (BMD) and fracture or fall risk; and the identification of potential harms of vitamin D above current reference intakes. Data sources MEDLINE(R) (1966-June Week 3 2006); Embase (2002-2006 Week 25); CINAHL (1982-June Week 4, 2006); AMED (1985 to June 2006); Biological Abstracts (1990-February 2005); and the Cochrane Central Register of Controlled Trials (2nd Quarter 2006). Review methods Two independent reviewers completed a multi-level process of screening the literature to identify eligible studies (title and abstract, followed by full text review, and categorization of study design per key question). To minimize bias, study design was limited to randomized controlled trials (RCTs) wherever possible. Study criteria for question one were broadened to include observational studies due to a paucity of available RCTs, and question four was restricted to systematic reviews to limit scope. Data were abstracted in duplicate and study quality assessed. Differences in opinion were resolved through consensus or adjudication. If clinically relevant and statistically feasible, meta-analyses of RCTs on vitamin D supplementation and bone health outcomes were conducted, with exploration of heterogeneity. When meta-analysis was not feasible, a qualitative systematic review of eligible studies was conducted. Results 167 studies met our eligibility criteria (112 RCTs, 19 prospective cohorts, 30 case-controls and six before-after studies). The largest body of evidence on vitamin D status and bone health was in older adults with a lack of studies in premenopausal women and infants, children and adolescents. The quality of RCTs was highest in the vitamin D efficacy trials for prevention of falls and/or fractures in older adults. There was fair evidence of an association between low circulating 25(OH)D concentrations and established rickets. However, the specific 25(OH)D concentrations associated with rickets is uncertain, given the lack of studies in populations with dietary calcium intakes similar to North American diets and the different methods used to determine 25(OH)D concentrations. There was inconsistent evidence of an association of circulating 25(OH)D with bone mineral content in infants, and fair evidence that serum 25(OH)D is inversely associated with serum PTH. In adolescents, there was fair evidence for an association between 25(OH)D levels and changes in BMD. There were very few studies in pregnant and lactating women, and insufficient evidence for an association between serum 25(OH)D and changes in BMD during lactation, and fair evidence of an inverse correlation with PTH. In older adults, there was fair evidence that serum 25(OH)D is inversely associated with falls, fair evidence for a positive association with BMD, and inconsistent evidence for an association with fractures. The imprecision of 25(OH)D assays may have contributed to the variable thresholds of 25(OH)D below which the risk of fractures, falls or bone loss was increased. There was good evidence that intakes from vitamin D-fortified foods (11 RCTs) consistently increased serum 25(OH)D in both young and older adults. Eight randomized trials of ultraviolet (UV)-B radiation (artificial and solar exposure) were small and heterogeneous with respect to determination of the exact UV-B dose and 25(OH)D assay but there was a positive effect on serum 25(OH)D concentrations. It was not possible to determine how 25(OH)D levels varied by ethnicity, sunscreen use or latitude. Seventy-four trials examined the effect of vitamin D(3) or D(2) on 25(OH)D concentrations. Most trials used vitamin D(3), and the majority enrolled older adults. In three trials, there was a greater response of serum 25(OH)D concentrations to vitamin D(3) compared to vitamin D(2), which may have been due to more rapid clearance of vitamin D(2) in addition to other mechanisms. Meta-analysis of 16 trials of vitamin D(3) was consistent with a dose-response effect on serum 25(OH)D when comparing daily doses of /= 400 IU. An exploratory analysis of the heterogeneity demonstrated a significant positive association comparable to an increase of 1 - 2 nmol/L in serum 25(OH)D for every 100 additional units of vitamin D although heterogeneity remained after adjusting for dose. Vitamin D(3) in combination with calcium results in small increases in BMD compared to placebo in older adults although quantitative synthesis was limited due to variable treatment durations and BMD sites. The evidence for fracture reduction with vitamin D supplementation was inconsistent across 15 trials. The combined results of trials using vitamin D(3) (700 - 800 IU daily) with calcium (500 - 1,200 mg) was consistent with a benefit on fractures although in a subgroup analysis by setting, benefit was primarily in elderly institutionalized women (fair evidence from two trials). There was inconsistent evidence across 14 RCTs of a benefit on fall risk. However, a subgroup analysis showed a benefit of vitamin D in postmenopausal women, and in trials that used vitamin D(3) plus calcium. In addition, there was a reduction in fall risk with vitamin D when six trials that adequately ascertained falls were combined. Limitations of the fall and fracture trials included poor compliance with vitamin D supplementation, incomplete assessment of vitamin D status and large losses to follow-up. We did not find any systematic reviews that addressed the question on the level of sunlight exposure that is sufficient to maintain serum 25(OH)D concentrations but minimizes risk of melanoma and non-melanoma skin cancer. There is little evidence from existing trials that vitamin D above current reference intakes is harmful. In most trials, reports of hypercalcemia and hypercalciuria were not associated with clinically relevant events. The Women's Health Initiative study did report a small increase in kidney stones in postmenopausal women aged 50 to 79 years whose daily vitamin D(3) intake was 400 IU (the reference intake for 50 to 70 years, and below the reference intake for > 70 years) combined with 1000 mg calcium. The increase in renal stones corresponded to 5.7 events per 10,000 person-years of exposure. The women in this trial had higher calcium intakes than is seen in most post-menopausal women. 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.

http://www.reboundhealth.com/cms/images/pdf/MedicalAbstract/effectiveness%20and%20safety%20of%20vitamin%20d%20in%20relation%20to%20bone%20health%20id%2016060.pdf

Effectiveness and safety of vitamin D in relation to bone health.

Background. Prostate cancer is the most prevalent nonskin cancer among men in the United States and is the second leading cause of cancer deaths in men, The cause of prostate cancer remains obscure. Recently it was hypothesized that low levels of vitamin D, a hormone with potent antitumor properties, may increase the risk for clinical prostate cancer.

Methods. Because the major source of vitamin D is casual exposure to ultraviolet (UV) radiation, the authors examined the geographic distributions of UV radiation and prostate cancer mortality in 3073 counties of the contiguous United States using linear regression and trend surface analyses.

Results. The geographic distributions of UV radiation and prostate cancer mortality are correlated inversely (P < 0.0001). Prostate cancer mortality exhibits a significant north-south trend, with lower rates in the South. These geographic patterns are not readily explicable by other known risk factors for prostate cancer.

Conclusions. These data lend support to the hypothesis that UV radiation may protect against clinical prostate cancer. Viewed in conjunction with other recent data, including those demonstrating a differentiating effect of vitamin D on human prostate cancer cells, these findings suggest that vitamin D may have an important role in the natural history of prostate cancer.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819921215%2970%3A12%3C2861%3A%3AAID-CNCR2820701224%3E3.0.CO%3B2-G

Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation.

https://www.amjmed.com/article/0002-9343(92)90682-2/pdf

Differences in vitamin D status between countries in young adults and the elderly.

The serum and urinary calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and parathyroid hormone (PTH) were studied in healthy black and white males living in Belgium, and the results were compared to data in blacks of similar age living in Zaire. Dietary calcium and vitamin D were estimated in a subsample of blacks and whites examined in Belgium. Compared to whites (9.51±0.28 mg%) serum calcium was somewhat lower in blacks (9.26±0.27 mg% in Belgium; 9.19±0.48 mg% in Zaire). The 24 hour urinary calcium excretion averaged 215.0±16.7 mg% in whites and was higher (P<0.05 or less) than in blacks (115±71 mg% in Belgium; 36±33 mg% in Zaire). The serum 25OHD levels were similar in whites and blacks evaluated in Zaire, both being higher (P<0.05 or less) than in blacks living in Belgium. In the latter blacks, an inverse correlation was observed between the 25OHD level and the duration of the stay in a temperate climate. Parathyroid hormone levels were slightly higher in blacks living in Belgium than in the other two groups of subjects. The serum levels of 1,25(OH)2D3 and human vitamin D-binding protein were similar in the three groups of subjects. Dietary calcium averaged 541±152 mg/day in blacks and was significantly (P<0.001) less than in whites (1,203±508 mg/day), whereas no significant difference was observed in dietary vitamin D intake between blacks and whites. It is concluded that calcium intake is low in blacks but stimulation of parathyroid hormone and 1,25(OH)2D3 required to achieve normocalcemia does not occur.

Calcium, vitamin D-endocrine system, and parathyroid hormone in black and white males

Summary Objective To assess the prevalence of cardiovascular risk factors in adult urban and rural Congolese subjects. Methods We obtained anthropometric data and information on life habits and medical history in 699 people ≥ 20 years, 444 in an urban, 255 in a rural setting. We determined the body mass index and recorded two blood pressure measurements that were averaged for analysis. Hypertension was BP ≥ 140/90 mmHg, awareness and/or use of antihypertensive treatment. Diabetes mellitus was self-reported diagnosis or a casual glycemia ≥ 200 mg/dL. We assessed the probability of hypertension in stepwise multiple logistic analysis, and awareness, and control of hypertension. Results We found higher ( P P P  55 years: 2.35; P P P Conclusions Our results indicate a heavy burden of uncontrolled risk factors in the Congolese population the potential complications of which run at a high mortality rate. They highlight the need for reasonable prevention measures at the population level.

Hypertension artérielle chez l’adulte Congolais du Sud Kivu : résultats de l’étude Vitaraa

Blood pressure and anthropometric characteristics were studied in 312 rural and 675 urban Bantu of Zaire aged 10 years and more; proteinuria and the urinary sodium to potassium ratio were determined. On average, systolic and diastolic pressure were higher in rural than in urban Bantu, and rose with advancing age in both populations. However, rural Bantu were older, lighter and smaller, and had a lower sodium:potassium ratio than urban Bantu. Using multiple regression analysis, systolic and diastolic pressures correlated positively with age, weight, pulse rate, sex and sodium:potassium ratio; diastolic pressure also correlated negatively to height. After adjusting blood pressure for these independent correlates, systolic pressure remained significantly higher in rural Bantu. However, no significant difference persisted between the two populations after adjusting blood pressure for age alone. The prevalence of hypertension in rural and urban Bantu increased with age and was 14.2 and 9.9%, respectively, for participants at least 20 years old; women were more affected in the rural area, whereas men were more affected in the urban population. The occurrence of proteinuria was higher in rural Bantu than in urban; it was similar in participants with and without definite hypertension. It is suggested that higher blood pressure in the rural setting was mostly accounted for by the older age of the population.

Correlates of blood pressure in rural and urban Zaïre.

The 24-hour urinary excretion of sodium, potassium, calcium, and magnesium and their relationship to arterial blood pressure were investigated from December 1983 to May 1984 in a 10% random sample (n = 666) of urban Bantu of Kinshasa, Zaire. In youths aged 10-19 years, blood pressure averaged 109/60 mmHg, and the 24-hour urinary excretion of sodium, potassium, calcium, and magnesium averaged 84 mmol, 30 mmol, 483 mumol, and 2 mmol, respectively. After adjustment for age and body weight, a weak positive association became apparent between diastolic pressure and the urinary sodium to potassium ratio in girls and all youths. In adults aged greater than or equal to 20 years, blood pressure averaged 124/72 mmHg, and the 24-hour urinary excretion of sodium, potassium, calcium, and magnesium averaged 87 mmol, 33 mmol, 828 mumol, and 1.88 mmol, respectively. After adjustment for sex, age, body weight, and pulse rate in all adults, systolic pressure was significantly and positively correlated with urinary sodium excretion and negatively correlated with urinary potassium excretion, while diastolic pressure was weakly associated with urinary calcium excretion. In women, an independent and significant association was also observed between systolic pressure and 24-hour urinary sodium. When instead of the 24-hour urinary excretion of sodium and potassium, the sodium to potassium ratio was considered as an independent variable in multiple regression analysis, both systolic and diastolic pressure were independently and positively related to the sodium to potassium ratio in all adults. These results indicate that in this urban Bantu population, age and body weight are the major predictors of systolic pressure in youths and the major predictors of both systolic and diastolic pressure in adults. The sodium to potassium ratio did contribute to the prediction of blood pressure in girls and when, in youths as well as in adults, both sexes were considered together. Urinary calcium was associated with diastolic pressure only in all adults.

J R M'Buyamba-Kabangu

Papers

Calcium, vitamin D-endocrine system, and parathyroid hormone in black and white males

Hypertension artérielle chez l’adulte Congolais du Sud Kivu : résultats de l’étude Vitaraa

Correlates of blood pressure in rural and urban Zaïre.

Blood pressure and urinary cations in urban bantu of zaire

In-hospital mortality among black patients admitted for hypertension-related disorders in Mbuji Mayi, Congo.