Vitamin B2 (Riboflavin)BackgroundRiboflavin, or vitamin B2, plays a key role in energy metabolism. It is a central component of the coenzymes flavin mononucleotide and flavin adenine dinucleotide (FAD). Each of these coenzymes is essential for several reduction–oxidation enzymes. Flavins can accept a pair of hydrogen ions, and as such, act as oxidizing agents.The RDA for riboflavin is 1.3 mg/day in males and 1.1 mg/day in females [4]. The upper limit (UL) for toxicity is unknown. Riboflavin is found in organ meats, milk, bread products and fortified cereal.General PopulationRiboflavin deficiency is characterized by angular stomatitis, cheilosis and glossitis and typically occurs in association with other vitamin deficiencies. There is no known riboflavin toxicity.Riboflavin status is determined by the erythrocyte glutathione reductase activation coefficient (EGRac). This functional assay measures the activity of glutathione reductase before (EGRo) and after in vitro reactivation with FAD. The EGRac is calculated as the ratio of FAD-stimulated to un-stimulated enzyme activity and reflects tissue status [20]. An EGRac above 1.3 suggests riboflavin deficiency.People with Low Glomerular Filtration Rate & End-Stage Renal DiseaseRiboflavin status was measured in 43 HD patients who had previously received a low-dose supplement containing folic and ascorbic acid. The EGRac was normal in all patients whilst approximately 10% of patients had insufficient EGRo values [5]. In a study of vitamin-supplemented (postdialysis vitamin containing 1.7 mg of riboflavin) dialysis patients, no significant differences in EGRac were noted when patients on standard three-times-weekly hemodialysis or nocturnal dialysis were compared with healthy controls [20]. Finally, in a supplemented group of HD patients (postdialysis multivitamin containing 20 mg riboflavin), no case of riboflavin deficiency was identified [10].The dialyzability of riboflavin has been studied in a group of 30 dialysis patients. There was a 7% reduction in total riboflavin (including FAD, FMN and free riboflavin) postdialysis with no differences between high- and low-flux membranes [11].SummaryThe available evidence suggests that riboflavin deficiency is uncommon in dialysis patients. There are no clinical trials evaluating riboflavin supplementation in dialysis patients and no recommendations for supplementation. No strong evidence exists for supplementation, but studies documenting sufficiency were performed in patients receiving supplements.Vitamin B3 (Niacin = nicotinic acid; niacinamide = nicotinamide)BackgroundVitamin B3 is crucial in the synthesis of carbohydrates, proteins, and fatty acids and therefore plays key role in energy metabolism.Niacin and niacinamide are the two physiologically equivalent forms, although niacinamide lacks the pharmacologic effects of niacin (it does not lower cholesterol or cause flushing). Within the mitochondria, niacin, nicotinamide, and tryptophan form nicotinamide adenine dinuceotide (NAD) and NAD phosphate (NADP). These are the active forms of niacin and many enzymatic reactions depend upon them. The niacin component can either accept electrons or donate hydrogen ions and, as such, are crucial in the synthesis of carbohydrates, proteins, and fatty acids.General PopulationThe RDA for niacin is 16 mg/day in males and 14 mg/day in females. The UL of toxicity of niacin is 35 mg/day [4]. Niacin is readily found in meat, fish, poultry, and enriched whole grain products. Niacin is an accepted treatment for the reduction of total and LDL-cholesterol in the general population [21, 22]. The main side effect of supplementation with niacin is the flushing reaction associated with nicotinic acid, a symptom that can be reduced with sustained release preparations [23].Deficiency and toxicity of vitamin B3: Deficiency of niacin results in a photosensitive pigmented dermatitis called pellagra. Although common in the 1800s, this now only exists in developed countries as a complication of alcoholism, anorexia, or malabsorptive disease. In the general population, niacin toxicity has included GI symptoms as well as elevated transaminases and myopathy.People with Low Glomerular Filtration Rate & End-Stage Renal DiseaseThere are very few measures of niacin status in people with low glomerular filtration rate or ESRD. Whole blood niacin and erythrocyte niacin concentrations were measured monthly in 15 dialysis patients who were not taking a postdialysis multivitamin [7]. The niacin concentration in the whole blood was in the low-normal range and remained so for the duration of the 12-month follow-up. The erythrocyte niacin concentration was normal in the majority of these patients throughout the period of observation.In a rodent model of CKD, nicotinamide was demonstrated to inhibit the NaPi-2b sodium-dependent phosphate cotransporter within the GI tract [24]. It has therefore been studied as a phosphorus-lowering agent in people with low GFR because of its potential to impair absorption of dietary phosphate [25, 26]. As attractive as such a drug may appear, the metabolism of niacin and nicotinamide in individuals with low GFR has not been well studied; there is preliminary evidence that a metabolite of nicotinamide, N-methyl-2-pyridine-5-carboxamide, may in fact accumulate and be a uremic toxin [27-29].Niacin levels do not change pre- and post a single hemodialysis treatment [12]. Whether niacin is present in the dialysate has not been studied. As it does not circulate as a free compound, it is plausible that it is not dialyzable.SummaryThere are no trials utilizing niacin that have studied a clinical endpoint. The available evidence suggests that niacin could potentially accumulate in dialysis patients, and long-term safety in this population is unclear. Given the potential for modifying phosphorus absorption with simultaneous lipid lowering, studies of both short- and long-term tolerability and toxicity are required. There is no recommendation for niacin prescription for individuals with low GFR or ESRD.
Water soluble vitamins (summary)
Vitamin B2 (Riboflavin), Vitamin B3 (Niacin = nicotinic acid; niacinamide = nicotinamide)
Vitamin B7 (biotin), Vitamin B9 (folic acid, folate)
Clase, C. M., Ki, V. and Holden, R. M. (2013), Water-Soluble Vitamins in People with Low Glomerular Filtration Rate or On Dialysis: A Review. Seminars in Dialysis, 26: 546–567. doi: 10.1111/sdi.12099
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