Dr. Ron’s Research Review – August 12, 2020

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This week’s research review focuses on vitamin D and phosphate.

Low-Phosphate Diet

A study found the increase in serum 1,25(OH)2D3 level in adult rats during short-term low-phosphate diet treatment is likely to be mediated by a decrease in metabolic clearance via the down-regulation of both renal 24-OHase and VDR expression. (Chau et al., 2005)

Dietary Phosphate

The main food sources of phosphate are the protein-rich food groups, including dairy products, meat, and fish. Phosphate is the main component of many preservatives and additive salts found in processed food. (Erem and Razzaque, 2018)
Common sources of inorganic phosphate include certain beverages, enhanced or restructured meats, frozen meals, cereals, snack bars, processed or spreadable cheeses, instant products, and refrigerated bakery products. (Erem and Razzaque, 2018)
Uncooked meat and poultry products that are enhanced may contain additives that increase phosphorus and potassium content by as much as almost two- and three-fold, respectively; this modification may not be discernible from inspection of the food label. These foods used words on the package labeling including: “enhanced,” “cured,” “contains solution,” and “natural flavorings.” (Sherman and Mehta, 2009)
Foods highest in phosphorus include the following.
Fast foods, foods sold at gas stations, and other packaged and convenience foods
Processed cheeses, such as American cheese and cheese spreads
Fresh or frozen meats that have added flavor or fluids to keep them moist
Cola and pepper-type sodas, many flavored waters, bottled teas, energy or sports drinks, many powdered drink mixes, beer, and wine

Limiting Phosphorus-Containing Food Additives

Phosphorus-containing additives are increasingly being added to processed and fast foods.
A study published in JAMA determined the effect of limiting the intake of phosphorus-containing food additives on serum phosphorus levels among patients with end-stage renal disease
Two hundred seventy-nine patients with elevated baseline serum phosphorus levels (>5.5 mg/dL) were randomly assigned to an intervention or control group. Intervention participants (n=145) received education on avoiding foods with phosphorus additives when purchasing groceries or visiting fast food restaurants. Control participants (n=134) continued to receive usual care. Changes in serum phosphorus level were measured after 3 months.
At baseline, there was no significant difference in serum phosphorus levels between the 2 groups. After 3 months, the decline in serum phosphorus levels was 0.6 mg/dL larger among intervention vs control participants (95% confidence interval, -1.0 to -0.1 mg/dL). Intervention participants also had statistically significant increases in reading ingredient lists (P<.001) and nutrition facts labels (P = .04) but no significant increase in food knowledge scores (P = .13).
Educating end-stage renal disease patients to avoid phosphorus-containing food additives resulted in modest improvements in hyperphosphatemia. (Sullivan et al., 2009)

Activated Charcoal

A study observed and recorded the effects of oral activated charcoal (OAC) on hyperphosphatemia and vascular calcification in stage 3-4 chronic kidney disease (CKD).
In a randomized controlled study, we included 97 patients with stage 3-4 CKD. In the first phase of the experiment, the patients were randomly divided into the oral activated charcoal group and placebo group. The endpoint of this phase was the development of hyperphosphatemia. The patients with hyperphosphatemia were selected into the second phase of the study. These patients underwent coronary artery multi-detector computed tomography (MDCT) and were randomly divided into three groups: the oral activated charcoal, the calcium carbonate (CC) group and the lanthanum carbonate (LC) group. The first and second phases of the experiment were followed for 12 months.
In the first phase of the experiment, there was a statistically significant difference in the proportion of patients with hyperphosphatemia between the oral activated charcoal and placebo groups (28.57% vs. 79.17%, X^2^ = 24.958, P = 0.000). In the second phase, the differences in coronary calcification score (CACS) between the oral activated charcoal group, the calcium carbonate group and the lanthanum carbonate group were statistically significant (525.5 ± 104.2 vs 688.1 ± 183.7 vs 431.4 ± 122.5, P < 0.01).
Oral activated charcoal effectively delays the onset of hyperphosphatemia in patients with chronic kidney disease. Oral activated charcoal appears to delay the development of vascular calcifications in stage 3-4 CKD patients. (Gao et al., 2019)

Dr. Ron

 


Articles

 

Age-related alteration of vitamin D metabolism in response to low-phosphate diet in rats.
            (Chau et al., 2005)  Download
The responses of renal vitamin D metabolism to its major stimuli alter with age. Previous studies showed that the increase in circulating 1,25-dihydroxyvitamin D (1,25(OH)2D3) as well as renal 25-hydroxyvitamin D3 1-alpha hydroxylase (1-OHase) activity in response to dietary Ca or P restriction reduced with age in rats. We hypothesized that the mechanism involved in increasing circulating 1,25(OH)2D3 in response to mineral deficiency alters with age. In the present study, we tested the hypothesis by studying the expression of genes involved in renal vitamin D metabolism (renal 1-OHase, 25-hydroxyvitamin D 24-hydroxylase (24-OHase) and vitamin D receptor (VDR)) in young (1-month-old) and adult (6-month-old) rats in response to low-phosphate diet (LPD). As expected, serum 1,25(OH)2D3 increased in both young and adult rats upon LPD treatment and the increase was much higher in younger rats. In young rats, LPD treatment decreased renal 24-OHase (days 1-7, P<0.01) and increased renal 1-OHase mRNA expression (days 1-5, P<0.01). LPD treatment failed to increase renal 1-OHase but did suppress 24-OHase mRNA expression (P<0.01) within 7 d of LPD treatment in adult rats. Renal expression of VDR mRNA decreased with age (P<0.001) and was suppressed by LPD treatment in both age groups (P<0.05). Feeding of adult rats with 10 d of LPD increased 1-OHase (P<0.05) and suppressed 24-OHase (P<0.001) as well as VDR (P<0.05) mRNA expression. These results indicate that the increase in serum 1,25(OH)2D3 level in adult rats during short-term LPD treatment is likely to be mediated by a decrease in metabolic clearance via the down-regulation of both renal 24-OHase and VDR expression. The induction of renal 1-OHase mRNA expression in adult rats requires longer duration of LPD treatment than in younger rats.

Effects of oral activated charcoal on hyperphosphatemia and vascular calcification in Chinese patients with stage 3-4 chronic kidney disease.
            (Gao et al., 2019)  Download
BACKGROUND:  The relationship between oral activated charcoal (OAC) and hyperphosphatemia and vascular calcification is not completely clear. We observed and recorded the effects of OAC on hyperphosphatemia and vascular calcification in stage 3-4 chronic kidney disease (CKD). METHODS:  In a randomized controlled study, we included 97 patients with stage 3-4 CKD. In the first phase of the experiment, the patients were randomly divided into the OAC group and placebo group. The endpoint of this phase was the development of hyperphosphatemia. The patients with hyperphosphatemia were selected into the second phase of the study. These patients underwent coronary artery multidetector computed tomography (MDCT) and were randomly divided into three groups: the OAC group, the calcium carbonate (CC) group and the lanthanum carbonate (LC) group. RESULTS:  The first and second phases of the experiment were followed for 12 months. In the first phase of the experiment, there was a statistically significant difference in the proportion of patients with hyperphosphatemia between the OAC and placebo groups (28.57% vs. 79.17%, X^2^ = 24.958, P = 0.000). In the second phase, the differences in coronary calcification score (CACS) between the OAC group, the CC group and the LC group were statistically significant (525.5 ± 104.2 vs 688.1 ± 183.7 vs 431.4 ± 122.5, P < 0.01). CONCLUSION:  Oral activated charcoal effectively delays the onset of hyperphosphatemia in patients with chronic kidney disease. OAC appears to delay the development of vascular calcifications in stage 3-4 CKD patients.

Effect of food additives on hyperphosphatemia among patients with end-stage renal disease: a randomized controlled trial.
            (Sullivan et al., 2009)  Download
CONTEXT:  High dietary phosphorus intake has deleterious consequences for renal patients and is possibly harmful for the general public as well. To prevent hyperphosphatemia, patients with end-stage renal disease limit their intake of foods that are naturally high in phosphorus. However, phosphorus-containing additives are increasingly being added to processed and fast foods. The effect of such additives on serum phosphorus levels is unclear. OBJECTIVE:  To determine the effect of limiting the intake of phosphorus-containing food additives on serum phosphorus levels among patients with end-stage renal disease. DESIGN, SETTING, AND PARTICIPANTS:  Cluster randomized controlled trial at 14 long-term hemodialysis facilities in northeast Ohio. Two hundred seventy-nine patients with elevated baseline serum phosphorus levels (>5.5 mg/dL) were recruited between May and October 2007. Two shifts at each of 12 large facilities and 1 shift at each of 2 small facilities were randomly assigned to an intervention or control group. INTERVENTION:  Intervention participants (n=145) received education on avoiding foods with phosphorus additives when purchasing groceries or visiting fast food restaurants. Control participants (n=134) continued to receive usual care. MAIN OUTCOME MEASURE:  Change in serum phosphorus level after 3 months. RESULTS:  At baseline, there was no significant difference in serum phosphorus levels between the 2 groups. After 3 months, the decline in serum phosphorus levels was 0.6 mg/dL larger among intervention vs control participants (95% confidence interval, -1.0 to -0.1 mg/dL). Intervention participants also had statistically significant increases in reading ingredient lists (P<.001) and nutrition facts labels (P = .04) but no significant increase in food knowledge scores (P = .13). CONCLUSION:  Educating end-stage renal disease patients to avoid phosphorus-containing food additives resulted in modest improvements in hyperphosphatemia. TRIAL REGISTRATION:  clinicaltrials.gov Identifier: NCT00583570.

 

 


 

References

Chau, TS, et al. (2005), ‘Age-related alteration of vitamin D metabolism in response to low-phosphate diet in rats.’, Br J Nutr, 93 (3), 299-307. PubMed: 15877868
Erem, S and MS Razzaque (2018), ‘Dietary phosphate toxicity: an emerging global health concern.’, Histochem Cell Biol, 150 (6), 711-19. PubMed: 30159784
Gao, Y, et al. (2019), ‘Effects of oral activated charcoal on hyperphosphatemia and vascular calcification in Chinese patients with stage 3-4 chronic kidney disease.’, J Nephrol, 32 (2), 265-72. PubMed: 30588573
Sherman, RA and O Mehta (2009), ‘Phosphorus and potassium content of enhanced meat and poultry products: implications for patients who receive dialysis.’, Clin J Am Soc Nephrol, 4 (8), 1370-73. PubMed: 19628683
Sullivan, C, et al. (2009), ‘Effect of food additives on hyperphosphatemia among patients with end-stage renal disease: a randomized controlled trial.’, JAMA, 301 (6), 629-35. PubMed: 19211470