Iron, Vitamin B12, and Folate Deficiencies Have “Dreadful Consequences,” but Treatments Are Available

      Anemia is not a normal consequence of aging — it is an overlooked sign of underlying illness, so the approach should be to evaluate, delineate, and address the cause or causes, said T.S. Dharmarajan, MD, at the Annual Conference of AMDA – The Society for Post-Acute and Long-Term Care Medicine.
      Causes of anemia include renal insufficiency, chronic inflammation and disease, deficiencies of iron, folate, and/or B12, and unexplained causes. “And they’re not mutually exclusive. You should not be satisfied with eliminating one cause,” said Dr. Dharmarajan, professor of medicine at Albert Einstein College of Medicine and vice chairman of the Department of Medicine and clinical director of the Division of Geriatrics at Montefiore Medical Center (Wakefield campus) in the Bronx.
      “Anemia has dreadful consequences” that are well-documented in the literature, he said, including lethargy and weakness, reduced lower muscle strength, impaired gait and mobility, falls and fractures, worsened cognition, increased hospitalizations and lengths of stay, and worsened coronary artery disease (CAD) and left ventricular hypertrophy. Anemia is also now believed to worsen and predispose patients to chronic kidney disease, he said.
      Across studies, “anemia consistently increases the size of the heart, increases left ventricular hypertrophy, and worsens the manifestations of CAD and heart workload until you get heart failure,” Dr. Dharmarajan said, during a session on the management of chronic conditions.
      A 2017 prospective cohort study of over 32,000 outpatients with stable CAD in 45 countries showed that over four years of follow-up evaluations, low hemoglobin was an independent predictor of cardiovascular events and mortality, he noted (Am J Med 2017;130:720–730). “I’ve had a lot of experience with heart failure readmissions in quality improvement projects. About 30% to 40% of them are severely anemic, with a hemoglobin between 8 and 10 [g/100 mL]. Why are we not treating a basic [contributor] to heart failure?”
      A basic evaluation for anemia includes a history and physical examination; review of medications and dietary habits; assessment of stool for occult blood; renal function review through estimated glomerular filtration rate, ferritin levels, and transferrin saturation; assay of serum B12 and folic acid; and measure of reticulocyte count and indirect bilirubin. “This is very simple and within our means” as primary care providers and geriatricians, he said.
      An assessment of thyroid function is also now considered more of a standard than something to be individualized, he noted. Other components of the evaluation can be individualized, and may include the Coombs test to detect antibodies against red blood cells, serum protein electrophoresis, bone marrow studies, and upper and lower endoscopy. Endoscopy, he said, “comes up on the top of this list.”
      “I’m a primary care doctor, not a hematologist, and in at least 80% of my patients with anemia, I don’t need to make a referral. If I have to, the most common referral I make is to the gastroenterologist,” he said.
      Testing serum ferritin is important, but the results should be interpreted with caution because liver disease, pressure ulcers, and inflammatory conditions can all cause false elevations. It is also important to appreciate that dietary iron deficiency is rare. “Do not blame iron deficiency on age, and do not blame it on the diet,” he said.
      Treatment with one daily tablet of 300–325 mg of ferrous sulfate, typically for six months, usually will correct a deficiency. “If patients complain [of adverse gastrointestinal effects], I’ll negotiate and ask them if they can take it two to three days a week and have red meat on the other days,” he said. For best absorption, he advises taking iron tablets on an empty stomach and with orange juice for the vitamin C. When oral treatment fails, parenteral iron therapy administered every two to three months is indicated.
      Vitamin B12 deficiency is common among older adults (studies have pegged the prevalence from 15% to 25%). It can be caused by a host of factors, including atrophic gastritis, Crohn’s disease, pernicious anemia, strict vegetarianism, the use of metformin, and prolonged use of proton pump inhibitors.
      Unlike B12, folate is present in virtually all foods, but its availability falls when food is cooked with heat. Malnutrition/malabsorption is one cause of folate deficiency; others include excess utilization (e.g., psoriasis, hemolysis), excess loss (e.g., dialysis, liver disease), and heavy alcohol use, which inhibits enterohepatic circulation.
      Folate deficiency can be treated with 1 mg of folic acid daily, but cobalamin deficiency should be ruled out before treatment. “Make sure they’re not B12 deficient. If they are, the deficiency will be masked [by folic acid supplementation] and will progress,” he said.
      A blunted erythropoietin response to anemia is a primary reason for anemia caused by chronic disease, making it important to distinguish between anemia of chronic disease and iron deficiency, Dr. Dharmarajan said. In patients with chronic kidney disease, erythropoietin deficiency is the primary cause for anemia, though other causes may exist and should be ruled out, he said.
      Christine Kilgore is a freelance writer based in Falls Church, VA.