Impact of nutritional vitamin D supplementation on parathyroid hormone and 25-hydroxyvitamin D levels in non-dialysis chronic kidney disease: a Meta-analysis

Background Secondary hyperparathyroidism (SHPT) is a common and major complication in chronic kidney disease (CKD), reflecting the increase of parathyroid hormone (PTH) in response to reduced Vitamin D signaling and hypocalcemia. This meta-analysis evaluated the impact of nutritional vitamin D (NVD) (cholecalciferol or ergocalciferol) on SHPT-related biomarkers. Methods A systematic literature search was performed in PubMed to identify relevant randomized control trials (RCTs) to be included in the meta-analysis. Fixed and random effects models were used to pool study level results. Effects were studied within NVD study arms and relative to control groups (placebo/no treatment); the former in order to identify the effect of actively altering biomarkers levels. Results Reductions in PTH from supplementation with NVD were small when observed within the NVD study arms (pooled reduction: 10.5 pg/ml) and larger when compared to placebo/no treatment (pooled reduction: 49.7 pg/ml). NVD supplementation increased levels of vitamin D (25(OH)D) in both analyses (increase within NVD study arm: 20.6 ng/ml, increase versus placebo/no treatment: 26.9 ng/ml). While small and statistically non-significant changes in phosphate and fibroblast growth factor 23 (FGF23) were observed, NVD supplementation caused calcium levels to increase when compared versus placebo/no treatment (increase: 0.23 mg/dl). Conclusions Our results suggest that supplementation with NVD can be used to increase 25(OH)D to a certain extent, while the potential of NVD to actively reduce PTH in ND-CKD patients with SHPT is limited.

Knuckle Pigmentation as an Early Cutaneous Sign of Vitamin B12 Deficiency: A Case Report

Vitamin B12 deficiency can present with variable hematological, neuropsychiatric, and mucocutaneous changes. Hyperpigmentation, specifically involving the knuckles has been described in vitamin B12 deficiency, but usually,these patients are symptomatic with systemic manifestations like megaloblastic anemia, pancytopenia, or neurological deficits. Here, we are reporting a case of nutritional vitamin B12 deficiency, who presented with isolated knuckle pigmentation and was successfully treated with oral therapy. This case also highlights the importance of recognizing this cutaneous sign as an early marker of vitamin B12 deficiency; thereby enabling the clinician to treat the disease before it leads to irreversible neurological complications.

P0891META-ANALYSIS OF NUTRITIONAL VITAMIN D FOR THE TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN PATIENTS WITH NON-DIALYSIS CHRONIC KIDNEY DISEASE

Background and Aims Chronic kidney disease (CKD) is commonly associated with mineral and bone disorder (CKD-MBD). Secondary hyperparathyroidism (SHPT) is a critical component of CKD-MBD characterized by excessive PTH secretion and parathyroid hyperplasia. SHPT develops in CKD because of disturbances in CKD-MBD parameters such as increases in serum phosphate and fibroblast growth factor 23, and reductions in 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and serum calcium. Low vitamin D levels play a critical role in the development and progression of SHPT. Nutritional vitamin D (NVD) supplements are being frequently used to address SHPT, especially in early CKD. The objective of this meta-analysis (MA) was to evaluate the effectiveness of the NVDs cholecalciferol and ergocalciferol in reducing PTH and increasing 25(OH)D in patients with non-dialysis CKD (ND-CKD). Method A systematic literature search was performed in PubMed to identify relevant randomized control trials (RCTs) to be included in the MA. All analyses were performed using both random and fixed effects models with inverted-variance weighting. Comparisons were made between the effects of NVDs relative to placebo-treated or untreated patients and between the baseline and end-of-study values of the patients treated with the NVDs, i.e. the effects in treated patients only. Results A total of 14 RCTs comprising 974 patients were included in the analyses. Overall reductions in PTH were small when compared to baseline (reduction of 10.95 pg/ml, 95 % confidence interval (CI): -15.99 to -5.91 pg/ml), while reductions in PTH were approximately three times larger when compared to placebo-treated or untreated patient groups (reduction of 34.35 pg/ml, 95 % CI:-47.47 to -21.24 pg/ml). This indicated a limited potential to actively lower PTH with NVDs as the relative effect on PTH when compared to placebo-treated or untreated patient groups was driven to a large degree by increases in PTH in the comparator arms. Treatment with NVDs tended to increase levels of 25(OH)D both when compared to placebo-treated or untreated patients (increase of 26.54 ng/ml, 95 % CI: 24.62 to 28.46 ng/ml) and when only the changes in treated patients were considered (increase of 21.49 ng/ml, 95 % CI: 20.54 to 22.44 ng/ml). However, large variations in effect sizes on levels of 25(OH)D were observed, making judgements about the size of any true treatment effect difficult. Average levels of 25(OH)D in treated patients at the end of the study period were >30 ng/ml in all but two RCTs and >50 ng/ml in only five of the included RCTs. No clear relationship was observed between study length (range: 4 to 144 weeks) or doses administered (range: 14 000 to 75 000 UI weekly average) and effects on 25(OH)D or PTH. Conclusion Our results suggest that treatment with NVDs is not efficacious to reliably and consistently lower PTH in ND-CKD patients with SHPT. Although treatment with NVDs can potentially be used to correct vitamin D insufficiency, our results suggest that the potential of NVD treatment to raise 25(OH)D levels to >50 ng/ml, a level needed to reduce PTH, is limited.

Identification of a New Variety of Avocados (Persea americana Mill. CV. Bacon) with High Vitamin E and Impact of Cold Storage on Tocochromanols Composition

(1) Background: Tocochromanols are a group of fat-soluble compounds including vitamin E (tocopherols and tocotrienols) and plastochromanol-8, and just one avocado can contain up to 20% of the required vitamin E daily intake. (2) Methods: HPLC and LC-MS/MS analyses were performed in avocados of various varieties and origin for the identification and quantification of tocopherols, tocotrienols and plastochromanol-8. After selection of the variety with the highest vitamin E content, we evaluated to what extent short- (4 h) and long-term (10 d) cold storage influences the accumulation of tocochromanols. (3) Results: Analyses revealed that “Bacon” avocados (Persea americana Mill. cv. Bacon) were the richest in vitamin E compared to other avocado varieties (including the highly commercialized Hass variety), and they not only accumulated tocopherols (with 110 µg of α-tocopherol per g dry matter), but also tocotrienols (mostly in the form of γ-tocotrienol, with 3 µg per g dry matter) and plastochromanol-8 (4.5 µg per g dry matter). While short-term cold shock did not negatively influence α-tocopherol contents, it increased those of γ-tocopherol, γ-tocotrienol, and plastochromanol-8 and decreased those of δ-tocotrienol. Furthermore, storage of Bacon avocados for 10 d led to a 20% decrease in the contents of α-tocopherol, whereas the contents of other tocopherols, tocotrienols and plastochromanol-8 were not affected. (4) Conclusions: It is concluded that Bacon avocados (i) are very rich in α-tocopherol, (ii) not only contain tocopherols, but also tocotrienols and plastochromanol-8, and (iii) their nutritional vitamin E value is negatively influenced by long-term cold storage.