For CKD Patients, B12 Supplementation May Be Helpful
Homocysteine (Hcy) is an intermediate metabolite in the conversion of methionine to cysteine. Elevated levels of Hcy are associated with increased levels of cardiovascular inflammation.
Hcy plays a role in platelet aggregation and stroke risk (Clin Nutr 2012;31:448-454). Additionally, the increase in inflammation associated with Hcy may be related to impaired glutathione production. Hcy levels correlate with increased glutathione transferase activity (Acta Diabetol 2013; published online ahead of print). Glutathione is made up of three amino acids that include cysteine.
Aside from genetic mutations, low intakes of vitamin B12, B6, and folate increase risk for hyperhomocysteinemia because they are required for the metabolism of methionine to cysteine. Due to cereal fortification with folic acid, folate levels are more typically adequate, but B12 levels are often inadequate due to a lack of sensitivity in testing (CMAJ 2005;172:1569-1573) as well as reduced B12 absorption through aging (CMAJ 2004;171:251-259).
Reduced B vitamin status may decrease the body's capability to formulate glutathione adequately. This loss would reduce the ability to mitigate oxidation damage in the body. Lipid peroxidation metabolites may proliferate, thereby increasing oxidative stress.
Chronic renal failure (CRF) is associated with a progressive increase in inflammatory factors as the disease progresses. Hcy increases concomitantly with other markers of inflammation in these patients (World J Nephrol 2013;2:31-37). Obese dialysis patients have an increased risk of atherosclerotic events in the presence of increased inflammation and Hcy (Nephrol Dial Transplant 2013;Suppl 4:iv188-iv194).
Hcy and cystatin C have been shown to be sensitive biomarkers for early urine microalbumin excretion in diabetic nephropathy (ISRN Endocrinol 2013;2013:407452). Interestingly, restless legs syndrome in dialysis patients has recently been found to be associated with Hcy status (Kidney Blood Press Res 2013;37:458-463).
A recent review found that supplementation with B6, B12, and folate did not reduce cardiovascular disease (CVD) risk in patients with chronic kidney disease (CKD), but it did decrease Hcy (Acta Med Indones 2013;45:150-156). This effect appears to only occur as long as supplementation continues (Int J Vitam Nutr Res 2012;82:260-266). Interestingly, other B vitamin interventions have found negative effects, such as increased rates of vascular events and kidney decline (JAMA 2010;303:1603-1609).
Typical B12 supplementation often uses the form of cyanocobalamin. A cyanide group is cleaved from this chemical, and the resultant cobalamin group is used to create one of two active forms. Methylcobalamin is the form needed for cysteine synthesis and glutathione production. In renal patients, the cyanide group has a higher tendency to accumulate due to the reduced glomerular filtration (Nephrol Dial Transplant 1997;12:1622-1628; Clin Chem Lab Med 2013;51:633-637). Glutathione is then required for the detoxification of cyanide. Supplementing with methylcobalamin may be more effective (Am J Kidney Dis 2010;55:1069-1078, but this supplement is more costly.Meat is among the primary food source of B12. Adequate stomach acid is required for pancreatic proteases to cleave the B12 from the meat and for subsequent absorption via intrinsic factor. Reduced stomach acid secretion is noted in aging populations (Nutrients 2010;2:299-316).
Additionally, long term use of proton pump inhibitors may be associated with reductions in B12 status, but data are still controversial (Curr Gastroenterol Rep 2010;12:448-457). B12 supplements do not require stomach acid for adequate absorption, and thus in older CRF patients who may have subclinical B12 deficiency, methylcobalamin may prove to be an adequate therapy for Hcy reduction.
Normal B12 ranges are typically 160-600 pmol/L, but due to the fact that only 6%-20% of the body's cobalamin is active, a serum value of 400 pmol/L must be met to ensure adequacy (Clin Chem 2009;55:2198-2206).