J Clin Invest. 1986 Jan;77(1):7-12.
Oral intake of phosphorus can determine the serum concentration of 1,25-dihydroxyvitamin D by determining its production rate in humans.
Portale AA, et al.
Changes in the oral intake of phosphorus could induce the reported changes in the serum concentration of 1,25-dihydroxyvitamin D (1,25-(OH)2D) by inducing changes in its production rate (PR) or metabolic clearance rate (MCR), or both. To investigate these possibilities, we employed the constant infusion equilibrium technique to measure the PR and MCR of 1,25-(OH)2D in six healthy men in whom the oral intake of phosphorus was initially maintained at 1,500 mg/70 kg body weight per d for 9 d, then restricted to 500 mg/d (coupled with oral administration of aluminum hydroxide) for 10 d, and then supplemented to 3,000 mg/d for 10 d. With phosphorus restriction, the serum concentration of 1,25-(OH)2D increased by 80% from a mean of 38 +/- 3 to 68 +/- 6 pg/ml, P less than 0.001; the PR increased from 1.8 +/- 0.2 to 3.8 +/- 0.6 micrograms/d, P less than 0.005; the MCR did not change significantly. The fasting serum concentration of phosphorus decreased from 3.5 +/- 0.2 to 2.6 +/- 0.2 mg/dl, P less than 0.01. With phosphorus supplementation, the serum concentration of 1,25-(OH)2D decreased abruptly, reaching a nadir within 2 to 4 d; after 10 d of supplementation, the mean concentration of 27 +/- 4 pg/ml was lower by 29%, P less than 0.01, than the value measured when phosphorus intake was normal. The PR decreased to 1.3 +/- 0.2 micrograms/d, P less than 0.05; the MCR did not change significantly. The fasting serum concentration of phosphorus increased significantly, but only initially. These data demonstrate that in healthy men, reductions and increases in the oral intake of phosphorus can induce rapidly occurring, large, inverse, and persisting changes in the serum concentration of 1,25-(OH)2D. Changes in the PR of 1,25-(OH)2D account entirely for the phosphorus-induced changes in serum concentration of this hormone.
Vitamin D3 positively affected by calcium intake:
Am J Clin Nutr. 2004 Dec;80(6 Suppl):1717S-20S.
Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system.
Cantorna MT, Zhu Y, Froicu M, Wittke A.
Vitamin D is an important immune system regulator. The active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], has been shown to inhibit the development of autoimmune diseases, including inflammatory bowel disease (IBD). Paradoxically, other immune system-mediated diseases (experimental asthma) and immunity to infectious organisms were unaffected by 1,25(OH)2D3 treatment. There are similar paradoxical effects of vitamin D deficiency on various immune system functions. Vitamin D and vitamin D receptor (VDR) deficiency resulted in accelerated IBD. Experimental asthma was unaffected by 1,25(OH)2D3 treatment and was less severe among VDR-deficient mice. Vitamin D is a selective regulator of the immune system, and the outcome of 1,25(OH)2D3 treatment, vitamin D deficiency, or VDR deficiency depends on the nature of the immune response (eg, infectious disease, asthma, or autoimmune disease). An additional factor that determines the effect of vitamin D status on immune function is dietary calcium. Dietary calcium has independent effects on IBD severity. Vitamin D-deficient mice on low-calcium diets developed the most severe IBD, and 1,25(OH)2D3 treatment of mice on low-calcium diets improved IBD symptoms. However, the best results for IBD were observed when the calcium concentration was high and 1,25(OH)2D3 was administered. Both the type of immune response and the calcium status of the host determine the effects of vitamin D status and 1,25(OH)2D3 on immunity.
Low Phophosphate Intake, Increases Vitamin D, Lowers Prostate Disease:
Indian J Exp Biol. 1999 Jul;37(7):623-6.
Phosphorus balance and prostate cancer.
Prostatic diseases affect men over the age of 45 and increase in frequency with age so that by the eighth decade more than 90% of men have Benign Prostatic Hyperplasia, (BPH), of which some progress to Carcinoma of Prostate (CaP). CaP, the most common malignancy in men, is also the second most common cause of death in men. Over the last three decades the mortality rate for CaP has steadily increased. There, however, are scant clues to the aetiology/pathogenesis of CaP. As treatment failures of advanced carcinoma continue to frustrate clinicians, emphasis has recently been focused on possible preventive strategies. Several studies support the view that higher levels of 1,25-(OH)2D, the active metabolite of vitamin D, reduce the risk of BPH and CaP. Men with high serum levels of 1,25-(OH)2D have a reduced risk of poorly differentiated and clinically advanced CaP. Hypercalcemic activity of 1,25-(OH)2D or its analogues, however, thwart their use for therapy in humans. Incidentally, a low dietary intake of phosphorus has been reported to increase serum levels of 1,25-(OH)2D. In addition, dietary fructose reduces plasma phosphate levels by 30 to 50% for more than 3 hr. Fruit intake has, indeed, been shown to be associated with reduced risk of CaP, particularly the advanced type. These observations, taken together, support that dietary determinants of hypophosphatemia, leading to increased plasma levels of 1,25-(OH)2D, could reduce the risk of ageing men to develop prostatic diseases, both BPH and/or carcinoma of Prostate.
Phosphorus intake over 1400 mg per day raises all-cause mortality.
Am J Clin Nutr February 2014 vol. 99 no. 2 320-327
High dietary phosphorus intake is associated with all-cause mortality: results from NHANES III
Alex R Chang, Mariana Lazo, Lawrence J Appel, Orlando M Gutiérrez, and Morgan E Grams
Background: Elevated serum phosphorus is associated with all-cause mortality, but little is known about risk associated with dietary phosphorus intake.
Objective: We investigated the association between phosphorus intake and mortality in a prospective cohort of healthy US adults (NHANES III; 1998–1994).
Design: Study participants were 9686 nonpregnant adults aged 20–80 y without diabetes, cancer, or kidney or cardiovascular disease. Exposure to dietary phosphorus, which was assessed by using a 24-h dietary recall, was expressed as the absolute intake and phosphorus density (phosphorus intake divided by energy intake). All-cause and cardiovascular mortality was assessed through 31 December 2006.
Results: Median phosphorus intake was 1166 mg/d (IQR: 823–1610 mg/d); median phosphorus density was 0.58 mg/kcal (0.48–0.70 mg/kcal). Individuals who consumed more phosphorus-dense diets were older, were less often African American, and led healthier lifestyles (smoking, physical activity, and Healthy Eating Index). In analyses adjusted for demographics, cardiovascular risk factors, kidney function, and energy intake, higher phosphorus intake was associated with higher all-cause mortality in individuals who consumed >1400 mg/d [adjusted HR (95% CI): 2.23 (1.09, 4.5) per 1-unit increase in ln(phosphorus intake); P = 0.03]. At <1400 mg/d, there was no association. A similar association was seen between higher phosphorus density and all-cause mortality at a phosphorus density amount >0.35 mg/kcal [adjusted HR (95% CI): 2.27 (1.19, 4.33) per 0.1-mg/kcal increase in phosphorus density; P = 0.01]. At <0.35 mg/kcal (approximately the fifth percentile), lower phosphorus density was associated with increased mortality risk. Phosphorus density was associated with cardiovascular mortality [adjusted HR (95% CI): 3.39 (1.43, 8.02) per 0.1 mg/kcal at >0.35 mg/kcal; P = 0.01], whereas no association was shown in analyses with phosphorus intake. Results were similar by subgroups of diet quality and in analyses adjusted for sodium and saturated fat intakes.
Conclusions: High phosphorus intake is associated with increased mortality in a healthy US population. Because of current patterns in phosphorus consumption in US adults, these findings may have important public health implications.