B Vitamins in Diabetes: Just "Expensive Urine"? (part 1)
B vitamins are essential vitamins in human nutrition. The most commonly referenced B vitamins include:
pantothenic acid (B5)
folic acid (rarely referred to as B9)
B vitamins are critical to normal cellular function, replication, repair, metabolism and energy production. Some B vitamins, particularly B1, B6 and B12, are especially important to normal nerve function and repair. In people with diabetes, often due to increased urination from the osmotic effects of high blood sugar, the water-soluble B vitamins may be lost more rapidly than in people without diabetes even if intake is technically adequate.
When reading supplement bottles or published descriptions of the functions of B vitamins, it is tempting to believe that we should be taking large quantities of B vitamins to “offset stress”, “improve energy”, “improve metabolism”, “assist in normal adrenal function”, etc. Unfortunately very little clinical trial research supports these claims. Few quality clinical trials have been performed on single B vitamins, let alone “B complex” combinations in diabetes.
Further complicating matters is homocysteine - a byproduct from protein/amino acid metabolism influenced by B vitamin intake - that has been implicated in causing direct damage to the thin endothelial lining of the small arteries particularly vulnerable in diabetes. Does lowering homocysteine actually reduce the risk of having a heart attack or stroke? Should homocysteine still be measured and checked?
In Part 1 of this article I will highlight the role of B vitamins in diabetes, focusing on those for which we have the most clinical research data (thiamine, niacin, biotin and vitamin B12). Next month, in Part 2 of this article I will discuss the state of the science regarding homocysteine, discuss special considerations in diabetes and give my opinion on when extra B vitamins are appropriate.
Thiamine is a water-soluble vitamin essential for normal metabolism of fat, glucose and protein as it is involved in key pathways of cellular energy synthesis. Specifically, thiamine is a cofactor in the actions of the enzymes:
pyruvate dehydrogenase and alpha-ketoglutarate decarboxylase in the breakdown of carbohydrates,
branched chain alpha-keto acid dehydrogenase in the metabolism of some amino acids,
and transketolase which acts to breakdown more complex sugars for energy production.
Abnormalities of transketolase activity have been identified in diabetes, and are partially responsible for the accumulation of sorbitol contributing to cataract formation.
In addition, classic thiamine deficiency has been long associated with heavy alcohol consumption and is known to cause Wernicke’s encephalopathy, a condition marked by nervous system symptoms including numbness, tingling and muscle weakness.
Thiamine can be found in fortified wheat products, lentils, peas, pork, brazil nuts, pecans, spinach, cantaloupe, pork, milk and eggs.
In recent studies, 75% of patients with diabetes were shown to have reduced levels of thiamine and increased urinary excretion of thiamine relative to controls. Low thiamine levels correlated with increased levels of vascular adhesion molecules, known markers of vascular disease and dysfunction. In a clinical trial performed by Arora et al., intravenous administration of thiamine improved functioning of the inner, endothelial lining of small arteries in patients with diabetes during induced hyperglycemia, reinforcing the role of thiamine in normal vascular function . In addition, a randomized, controlled trial of thiamine (25mg/day) combined with pyridoxine (B6) (50 mg/day) in patients with diabetes demonstrated significant improvements in perceived pain, numbness and paraesthesia (extra nerve sensations).
Recently, a fat-soluble, synthetic form of thiamine called benfotiamine has become available as a nutritional supplement. Interesting research exists on benfotiamine, including research that suggest benfotiamine protects the small and large arteries from the damage caused by elevated blood glucose and increased advanced glycosylation endproduct consumption in food (See Complementary Corner December 2006). Benfotiamine appears to be better absorbed than standard water-soluble thiamine, however high dose thiamine appears to have a similar effect and may have advantages. The jury is still out of the safety of benfotiamine, however only minimal safety concerns have been reported in the literature to date.
Niacin, or nicotinic acid, is another ubiquitous cofactor in human cellular energy production. Niacin functions as an intermediate, in the form of nicotinamide adenine dinucleotide (NADH), in reactions in glycolysis and the Kreb’s cycle, two fundamental energy production cycles in human biochemistry.
Niacin is also necessary for fat metabolism and normal DNA synthesis and repair in the form of nicotinamide adenine dinucleotide phosphate (NADPH).
Niacin, like thiamine, is water-soluble. Niacin deficiency, very rare in this country due to food fortification, is called pellagra.
Include animal foods, fortified wheat products, coffee, lima beans, lentils and peanuts.
Niacin is best known in medicine as a treatment for high blood cholesterol, or hypercholesterolemia. Niacin is available over-the-counter and as a prescription. The doses typically available in a B vitamin supplements range from 5-50 milligrams, whereas the doses used for cholesterol reduction range from 500-2500 milligrams. Most cholesterol lowering treatments impact only one risk factor; niacin has advantages over other cholesterol-lowering because it lowers LDL cholesterol, raises HDL cholesterol, tends to lower triglycerides and improves LDL particle size and lowers lipoprotein a (Lpa), an additional risk factor of cardiovascular disease [6, 7]. (See Complementary Corner 11/06 for more information on cholesterol and the importance of healthy levels).
In other studies, people with diabetes taking niacin had less progression of the artherosclerosis than those taking placebo, despite poor blood glucose control. Niacin accomplishes these excellent effects because it decreases clearance of HDL cholesterol in the liver and therefore more HDL is in circulation, scavenging less healthy LDL particles.
Niacin is considered a safe and effective treatment for hypercholesterolemia in patients with diabetes, especially at lower doses of 1000-1500 mg/day. Flushing is a common side effect of niacin treatment, and it can be quite uncomfortable for some people. However most people get used to the flushing and it typically does lessen in severity. Niacin treatment for high cholesterol (or low HDL cholesterol or high Lp(a)) should only be implemented with the supervision of a physician who can titrate your dose safely and monitor your cholesterol regularly to be sure it is working as expected.
In addition, niacin in higher doses can cause increases in liver enzymes, a sign of liver inflammation; since liver enzymes are commonly elevated in people with diabetes and the metabolic syndrome (due to deposition of fat in the liver), liver enzymes should be monitored periodically for elevations by a physician.
If you haven’t already figured this out, many of the B vitamins work together as co-factors in the function of many critical metabolic enzymes. Biotin is no exception. Biotin, like thiamine and niacin, is also required for normal function of:
pyruvate decarboxylase (an enzyme involved in carbohydrate and fat metabolism),
propionyl-coA carboxylase (an enzyme involved in fat metabolism),
and acetyl-coA carboxylase (also involved in carbohydrate and fat metabolism).
Biotin is known to bind to specific sites in these enzymes in order to optimize function, and supplementation of biotin is known to increase the activities of these enzymes in people with diabetes as well as those without diabetes[9, 10].
Food sources of biotin include animal products, avocado, wheat bran, baker’s yeast, raspberries, artichoke and cauliflower.
Most of the research available on biotin in diabetes comes from recent research supported by Nutrition 21, Inc., a company who manufacturers a nutritional supplement that is a combination of chromium picolinate and biotin (Diachrome®). Recent studies have demonstrated in people with diabetes, the combination of chromium picolinate and biotin resulted in an average 0.54% reduction in HbA1c, significant reductions in LDL and VLDL cholesterol and triglycerides [11-13].
Cobalamin, or vitamin B12, is required for normal nervous system functioning and normal cell proliferation. Vitamin B12 requires a special protein called intrinsic factor for its absorption (pernicious anemia, an autoimmune anemia, results when your body produces antibodies against intrinsic factor impeding absorption).
Intrinsic factor is produced by a special cell type in the lining of the stomach; as we age the lining of our stomach can atrophy or weaken. This atrophy can result in abnormal B12 absorption resulting in deficiency, thus older adults are particularly vulnerable to vitamin B12 deficiency.
Additionally another type of anemia, called a macrocytic anemia, results from vitamin B12 deficiency; macrocytic anemias are characterized by very large red blood cells (macrocytes, or large cells).
Vitamin B12 is also required for normal homocysteine metabolism, a topic covered in great detail in Part 2 of this article next month.
Sources of vitamin B12 include animal foods such as seafood, beef, pork, chicken, dairy products and eggs. Vegan (non-animal) sources of B12 are extremely limited. Some sources speculate spirulina is an adequate source of B12, however this may be due to contamination by small sea animals.
Vitamin B12 has been mostly studied in diabetes as treatment for neuropathies. In recent systematic review, vitamin B12 was found to be an effective treatment for diabetic peripheral neuropathy, with pain and paraesthestias reduced the most from treatment.>/p>
Also relevant to diabetes, metformin, the first-line prescription medication for treating elevated glucose in diabetes, is known to cause vitamin B12 deficiency and elevate homocysteine.
Conclusions (for now…)
As you can tell, the clinical research world has a lot of work to do in order to fully assess the benefits and risks of B vitamin intake and supplementation on the health of people with diabetes. Unfortunately, as is the case with many natural substances that are not patentable and therefore do not generate large profits, B vitamins are not of particular interest to most funding agencies.
Fortunately, innovative researchers do have friends like Diabetes Action to ensure vital research gets performed on important questions of optimal health in diabetes!
Read Part 2 where I will discuss the homocysteine debate in detail as well as offer my recommendations on when extra B vitamin supplementation may be worth trying!
Ryan Bradley, ND, MPH October 2007
LPI, Micronutrient Information Center. 2007.
Thornalley, P.J., et al., High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease. Diabetologia, 2007. 50(10): p. 2164-70.
Arora, S., et al., Thiamine (vitamin B1) improves endothelium-dependent vasodilatation in the presence of hyperglycemia. Ann Vasc Surg, 2006. 20(5): p. 653-8.
Abbas, Z.G. and A.B. Swai, Evaluation of the efficacy of thiamine and pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy. East Afr Med J, 1997. 74(12): p. 803-8.
Stirban, A., et al., Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care, 2006. 29(9): p. 2064-71.
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St Maurice, M., et al., Domain architecture of pyruvate carboxylase, a biotin-dependent multifunctional enzyme. Science, 2007. 317(5841): p. 1076-9.
Albarracin, C., et al., Combination of chromium and biotin improves coronary risk factors in hypercholesterolemic type 2 diabetes mellitus: a placebo-controlled, double-blind randomized clinical trial. J Cardiometab Syndr, 2007. 2(2): p. 91-7.
Albarracin, C.A., et al., Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes. Diabetes Metab Res Rev, 2007.
Geohas, J., et al., Chromium picolinate and biotin combination reduces atherogenic index of plasma in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Am J Med Sci, 2007. 333(3): p. 145-53.
Sun, Y., M.S. Lai, and C.J. Lu, Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials. Acta Neurol Taiwan, 2005. 14(2): p. 48-54.
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