September/October 2017

Nutrition-Focused Physical Exam: The Micronutrient Deficiency Detective
By Cora Martin, RDN, CSG, LD
Today's Geriatric Medicine
Vol. 10 No. 5 P. 22

Identifying and treating older adults' nutrient deficiencies is essential to ensuring optimal quality of life. Review of a patient's health history, environmental exposures, and potential polypharmacy can aid in unmasking nutrient deficiencies.

The world of genomic testing is allowing us to identify the particular genetic mutations that, when expressed, cause a deficiency. But this testing is often out of reach for many patients. It can be very expensive and often is not covered by health plans. Yet most of the micronutrient deficiencies that negatively impact our wellness can be treated at minimal cost.

This is where the nutrition-focused physical exam (NFPE) excels. NFPE training is offered through the Academy of Nutrition and Dietetics at hands-on workshops. It is a process designed to detect malnutrition signs and symptoms starting with a general observation, followed by a head-to-toe examination that includes physical observations, functional indicator assessments, and a patient interview. When conducting an exam, an observation may provoke further questioning, or a response to a habit or history question may incite further inspection. The NFPE process focuses extensively on body composition (eg, muscle, fat stores, fluid accumulation/deficit) and changes that have occurred in these areas. However, this article will explore the micronutrient deficiency component in the geriatric population.

How the NFPE Process Begins
Please allow me to share my journey. It was Mother's Day evening. I had just completed the NFPE training on the previous Friday, but I was excited and wanted to practice my new skills. I was particularly interested in assessing Anna, a newly admitted resident in a skilled nursing facility. She was nonverbal and did not participate in functional tasks. I was unable to obtain a diet history or insight into previous habits. Typically I would seek historical information from the family and close friends. However, she was admitted through Adult Protective Services, and no historian was available. As I assessed her for muscle and fat deficits, which were apparent, I was also attentive to signs of micronutrient deficiencies, especially vitamin B12 which, if deficient, could impact her cognitive function.

Initially I thought I could examine Anna physically, including her hair, skin, eyes, mouth (especially her tongue), and nails, and easily derive conclusions about Anna's nutritional state, but soon I discovered that her participation was essential to identify the micronutrient deficiencies most common in the elderly. In a skilled long term care setting, had I found indicators, I would follow up with a request for biochemical data. But even without biochemical support, supplementation can safely be initiated for most micronutrients, as adverse side effects are minimal. This may also apply if lab testing is expensive in comparison with the cost of treatment or if the testing is not reliable or is difficult to interpret, as the most recent research is suggesting with respect to vitamin D.

The heterogeneity of the group presents one of the greatest challenges in evaluating the geriatric population. Energy needs are lower than those of the younger population, yet many of the recommended micronutrient intakes may be comparable. A lifetime of different environmental exposures combined with an individual's potential polypharmacy play key roles in assessing for micronutrient deficiencies. The ability to obtain an accurate and comprehensive history is often key to identifying nutrient concerns.

Multiple studies of the elderly have found micronutrient intake inadequacies. The most commonly identified were vitamin D, calcium, and folic acid.1,2 Studies have also included vitamin E, iodine, magnesium, vitamin B6, and vitamin C in deficiency findings.2-4 Chernoff concluded that in elderly women, vitamin B12, vitamin A, vitamin C, vitamin D, calcium, iron, and zinc are among the most significant micronutrient deficiencies.5 Some of the most common are examined below.

Vitamin D and Calcium Deficiencies: Supplementation Controversies
History and identification of risk factors are more important than physical observations in assessing this area. The classic signs of vitamin D deficiency we may remember as bowed legs, knock knees, and rachitic rosary (like rosary beads along the rib cage). In older adults, a history of falls, broken bones, dental caries, muscle weakness, neuromuscular and endocrinal impairments including decline in cognitive function, depression, and chronic pain advocate for further investigation into vitamin D deficiency.6,7 Likewise, calcium inadequacy has been associated with osteoporosis, as well as colon cancer and hypertension.5 Improvement in muscle mass and function has been correlated with improving vitamin D levels.7 The examiner should inquire about height decreases, sun exposure, and high calcium/vitamin D food intake, such as vitamin D fortified milk and whether a bone density test has been performed. Aging negatively impacts the ability to achieve vitamin D adequacy. The skin's vitamin D production and intestinal absorption are reduced and renal cholecalciferol production is impaired, as it must undergo sequential hydroxylation in the liver and kidney to become biologically active. A lack of adequate sun exposure and reduced food intake also promote deficiency in an older adult.5,7,8

Many studies have looked at 25-hydroxyvitamin D (25[OH]D) levels. A level of less than 20 ng/ml is defined as deficiency, whereas 25(OH)D at 20 ng/mL to 30 ng/mL is defined as insufficiency, although the actual recommended cutoff points vary by health institution.9,10 A meta-analysis found a direct cross-sectional and longitudinal association between lower 25(OH)D concentrations and falls, specifically with concentrations <20 ng/mL, although the authors suggested additional well-designed randomized controlled trials.11 Measurement of 25(OH)D has become more common in long term care communities, but the interpretation of results presents challenges. Results depend not only on intake but also on sun exposure (season and latitude) and whether genetic variations have been expressed in the metabolic pathway, making it difficult to compare levels over time when evaluating the effectiveness of vitamin D therapy and the dosage of supplement indicated.

As with measurement of vitamin D, recommended therapy for correction of a deficiency varies from at least 1,000 IU vitamin D3 (cholecalciferol) daily taken orally to the Endocrine Society Clinical Practice Guideline suggesting supplementation with 50,000 IU of vitamin D2 (ergocalciferol) or D3 once weekly for eight weeks (or 6,000 IU daily) to achieve a blood level >30 ng/mL, followed by maintenance therapy of 1,500 IU to 2,000 IU per day. Some studies suggest that vitamin D2 and D3 forms are equivalent at low doses but that D3 is more effective at high doses.12 Studies have also implied that higher supplementation may be needed as an individual's weight increases.7,12 For the general population, Adequate Intake of vitamin D in individuals aged 51 to 70 is established at 400 IU and increases to 600 IU for those over the age of 70.

Vitamin D, calcium, vitamin K, and magnesium all play significant roles in bone mineralization. The Recommended Dietary Allowance for calcium increases to 1,200 mg per day for men over the age of 70 and women older than 50, as compared with 1,000 mg per day in younger adults. However, routine use of calcium supplementation has been questioned considering recent research and meta-analysis showing calcium supplementation increased the risk of cardiovascular events.7

Folate Deficiency: Impact of Fortified Foods
Rapidly dividing cells, such as those in the gastrointestinal tract and bone marrow, are impacted by folate deficiency. In its early stage, folate deficiency symptoms include fatigue, weakness, headache, impaired concentration, palpitations, diarrhea, sore red tongue with a smooth shiny surface, and yellow-tinged pallor.10 Remember that when observing a patient for color changes, it is best to use a natural light source. As the deficiency progresses, macrocytic red blood cells develop, and megaloblastic anemia presents. Increased folate losses occur in patients undergoing chronic dialysis and those with chronic hemolytic disease, exfoliative dermatitis, liver disease, alcohol abuse, celiac disease, and other small intestine malabsorption, including intestinal resection and weight loss surgery.10 Many medications can also interfere with folate metabolism including metformin, phenytoin, primidone, sulfasalazine, triamterene, methotrexate, and barbiturates.10,13

Folate deficiency is confirmed with low serum folate, low erythrocyte folate, and elevated plasma homocysteine.10

A more common genetic variant, the MTHFR SNP, affects a methylation metabolic pathway. Individuals with this condition can develop homocystinuria, a disorder that affects the eyes, joints, and other parts of the body. It is characterized by high homocysteine levels, which have been associated with heart disease and strokes. As Charis Eng, MD, PhD, points out, rather than perform the more expensive genetic test for this defect, check the homocysteine level in the blood. If it is normal, there is no need to proceed. If it is high, folate, vitamin B6, and vitamin B12 supplementation should be introduced as indicated.14

Recommended levels for folate are higher in the current Dietary Reference Intakes to reflect evidence that folate intake can lower the atherogenic rise in plasma homocysteine associated with aging.2

Prior to 1998, folate inadequacy was identified as a concern in a study that examined participants and nonparticipants in the Elderly Nutrition Program.15 As of 1998, the FDA has required folic acid fortification of a variety of grain products.4,7 This has had a positive impact on meeting folate needs in the geriatric population. However, a study published in 2010 investigating the micronutrient intakes of older adults attending senior centers in Kansas found that more than 71.5% of participants continued to have dietary folate intake below the recommended level and, of the study participants taking a folic acid supplement, more than 84% exceeded the Tolerable Upper Intake Level within the Dietary Reference Intake model, ie, 25.9% of the study participants.4 Although concerns have been raised about the risk of accelerating preneoplastic lesions with high-dose synthetic folate supplementation, the primary concern relates to vitamin B12. Before folate therapy is started, vitamin B12 adequacy should be confirmed, as it can mask vitamin B12 deficiency signs until irreversible nerve damage occurs.

Vitamin B12 Deficiency: Is It Underdiagnosed?
Often vitamin B12 (cobalamin) deficiency is unrecognized because of nonspecific polymorphic clinical manifestations.16 Vitamin B12 deficiency can pose significant adverse effects to organ systems with high cell turnover and metabolism such as the bone marrow, gastrointestinal tract, and brain.17 In large United States and United Kingdom surveys, close to 20% of adults aged 60 and older had marginal vitamin B12 status.18

Observable symptoms appear in the cutaneous, neuromuscular, and gastrointestinal areas. Cutaneous manifestations occur early in vitamin B12 deficiency and present as skin hyperpigmentation, including greater hyperpigmentation of the knuckles and interphalangeal joints than at the phalanges, vitiligo (loss of pigment in patches of skin), and angular stomatitis.19 Neuromuscular symptoms may include paresthesia, weakness, gait abnormalities/ataxia, missing ankle tendon jerks, and cognitive or behavioral changes, including depression, dementia, and fatigue. Many of these symptoms are consistent with the expectations of aging. Gastrointestinal symptoms include loss of appetite, diarrhea, and Hunter's glossitis (a swollen, beefy red, shiny tongue that is painful with a burning sensation).20 Other symptoms can include pallor, edema, shortness of breath, low blood pressure, impaired vibration sense, impaired position and cutaneous sensation, and weakness.17,19 Megaloblastic anemia and subacute combined degeneration of the spinal cord are also described in the later stages.17

A possible simple early test was described by Karanth.19 In Karanth's test, the skin color tone is measured at the interphalangeal joint and the phalanx of the index finger. The person to be screened is taken to a natural light source and the Von Luschan skin tone chart is used to compare the difference between the color readings. The reported limitation is that the study population was not equally distributed in the six Fitzpatrick types and that it needs to be verified in a larger population.

Multiple risk factors may contribute to development of a vitamin B12 deficiency. Among them are conditions that negatively impact unbinding of vitamin B12 from its protein carrier, thereby making it unavailable. These include atrophic gastritis with an increased prevalence associated with age, a reduction in stomach acid levels due to acid-suppressing medications such as proton pump inhibitors and H2 receptor antagonists, and the inability to adequately chew high-protein (high vitamin B12 content) foods, which may create large food particles that are inadequately bathed in digestive secretions. Bacterial overgrowth in the gut (small intestinal bacterial overgrowth or SIBO) may bind the B12, rendering it unavailable for absorption.5 Use of biguanides, such as metformin, reduces intestinal availability of free calcium ions for vitamin B12–intrinsic factor complex uptake by ileal cell membrane receptors.17 Cholestyramine, colchicine, and antibiotics, especially neomycin, interfere with vitamin B12 absorption from the intestine. Chronic alcohol abuse, history of gastric surgery, and the growing popularity of vegan diets should also be considered when evaluating an older adult for vitamin B12 deficiency.10,16,21

In a study of Dutch community-dwelling adults over the age of 65, dairy and meat were the most important contributors to serum vitamin B12 levels, followed by fish and shellfish. Milk intake was associated with the highest serum vitamin B12 concentrations, whereas egg intake did not significantly contribute to higher serum vitamin B12 concentrations.22 Considering the results of this study, it is important to confirm that milk alternatives such as soy and almond are vitamin B12 fortified, as those that are not fortified contain no vitamin B12. An additional bonus with fortified milk is that it contains a crystalline form of vitamin B12 that is not negatively impacted by conditions that alter stomach pH and vitamin B12 availability. The crystalline form of vitamin B12 is also used in oral supplements.

Historically, clinicians frequently used macrocytic erythrocytes as an indicator of vitamin B12 deficiency. However, up to 84% of cases would be missed if macrocytosis is used as the only parameter to screen for vitamin B12 deficiency, as noted in a 2015 review by Wong.17

Blood testing also presents challenges. There are formulas using vitamin B12-related lab data to identify deficiency more accurately; however, obtaining the multiple assays can be difficult and expensive. Plasma B12, methylmalonic acid (MMA), and homocysteine levels appear to be most commonly used. A plasma B12 level of 200 ng/L is typically set as the threshold for diagnosing deficiency.23 However, a false normal may occur with liver disease, myeloproliferative disorder, congenital transcobalamin II deficiency, and intestinal bacterial overgrowth.17 An MMA concentration of >750 nmol/L is generally accepted as definitively indicating B12 deficiency, but some laboratories identify a much lower value.17,23 The MMA level is elevated with vitamin B12 deficiency but not folate deficiency. A homocysteine concentration >20 mmol/L may suggest a B12 deficiency in folate-replete patients.23 Elevated serum homocysteine and MMA level (>3 standard deviations above the mean in normal subjects) has sensitivity over 95% to diagnose deficiency. However, the reference intervals for serum MMA and homocysteine are variable among different laboratories, and renal insufficiency can cause elevations in both MMA and homocysteine.17

Prompt treatment of vitamin B12 deficiency is necessary to avoid potentially irreversible neurological impact. This includes not only supplementation but also treatment or removal of the potential cause when possible. The unpredictable absorption by passive diffusion of oral vitamin B12 replacement makes recommendation of a standard dose difficult.17 Hence, intramuscular injection was historically used. A Cochrane review, however, supports the use of high-dose vitamin B12 (both 1 mg and 2 mg daily) to achieve hematological and neurological response in patients with pernicious anemia or with ileal resection with a maintenance dose of 1 mg daily. For patients with dietary insufficiency and food-cobalamin malabsorption, oral replacement is 1 mg daily for one month, and then 125 μg to 250 μg daily as a maintenance dose.17 Wong warns that even though vitamin B12 does not have side effects, hypokalemia, resulting from uptake of circulating potassium by newly growing and dividing hematopoietic cells, can be severe or sometimes life threatening. Transient potassium replacement at the initial stage of vitamin B12 replacement, especially in those with low-normal serum potassium, can prevent subsequent hypokalemia.17

Conclusion
This article has examined some of the more common nutrient deficiencies. Nutrient deficiencies should not be accepted as part of growing old. Each of us is unique in our biochemical composition and environmental exposure history. It should be a clinician's goal to optimize health as opposed to simply treating illness. Awareness by providers and early identification and treatment of nutrient concerns is consistent with this approach.

— Cora Martin, RDN, CSG, LD, is a registered dietitian nutritionist in Chardon, Ohio, and manages a dietetic consultation practice specializing in long term care communities. She is board certified in gerontological nutrition. Her mission is to bring integrative and functional nutrition to long term care communities, recognizing that strengthening assessment skills is an important first step.

INTERESTED IN LEARNING MORE?
• Challenge your knowledge base with Medscape CME ... Examining the Fingernails When Evaluating Presenting Symptoms in Elderly Patients (November 23, 2009).

• Attend a nutrition-focused physical exam workshop through the Academy of Nutrition and Dietetics.

• Read Nutrition Focused Physical Assessment: Making Clinical Connections by Mary D. Litchford, PhD, RD, LDN, and The Skin, Tongue and Nails Speak: Observational Signs of Nutritional Deficiencies by Donna Burka Wild.

• Keep a copy of Nutrition Focused Physical Exam Pocket Guide, edited by Beth Mordarski, RDN, LD, and Jodi Wolff, MS, RDN, LD, CNSC, FAND, with you for reference when rounding.

References
1. Fabian E, Elmadfa I. Nutritional situation of the elderly in the European Union: data of the European Nutrition and Health Report (2004). Ann Nutr Metab. 2008;52(Suppl 1):57-61.

2. Foote JA, Giuliano AR, Harris RB. Older adults need guidance to meet nutritional recommendations. J Am Coll Nutr. 2000;19(5):628-640.

3. Fritz K, Elmadfa I. Quality of nutrition of elderly with different degrees of dependency: elderly living in private homes. Ann Nutr Metab. 2008;52(Suppl 1):47-50.

4. Weeden A, Remig V, Holcomb CA, Herald T, Baybutt R. Vitamin and mineral supplements have a nutritionally significant impact on micronutrient intakes of older adults attending senior centers. J Nutr Elder. 2010;29(2):241-254.

5. Chernoff R. Micronutrient requirements in older women. Am J Clin Nutr. 2005;81(5):1240S-1245S.

6. Caillet P, Jaglal SB, Laforest L, et al. Impact of vitamin D supplementation on health-care use in a 25-hydroxyvitamin D-tested population in France: a population-based descriptive cohort study. Public Health Nutr. 2015;18(3):554-561.

7. Montgomery SC, Streit SM, Beebe ML, Maxwell PJ IV. Micronutrient needs of the elderly. Nutr Clin Pract. 2014;29(4):435-444.

8. Sakalli H, Arslan D, Yucel AE. The effect of oral and parenteral vitamin D supplementation in the elderly: a prospective, double-blinded, randomized, placebo-controlled study. Rheumatol Int. 2012;32(8):2279-2283.

9. Weisshof R, Chermesh I. Micronutrient deficiencies in inflammatory bowel disease. Curr Opin Clin Nutr Metab Care. 2015;18(6):576-581.

10. Litchford, MD. Nutrition Focused Physical Assessment: Making Clinical Connections. Greensboro, NC: CASE Software & Books; 2012.

11. Annweiler C, Beauchet O. Questioning vitamin D status of elderly fallers and nonfallers: a meta-analysis to address a 'forgotten step.' J Intern Med. 2015;277(1):16-44.

12. Grädel L, Merker M, Mueller B, Schuetz P. Screening and treatment of vitamin D deficiency on hospital admission: is there a benefit for medical inpatients? Am J Med. 2016;129(1):116.e111-116.e134.

13. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998.

14. Eng C. A genetic test you don't need. Cleveland Clinic website. https://health.clevelandclinic.org/2013/09/a-genetic-test-you-dont-need. Updated September 27, 2013. Accessed June 24, 2017.

15. Millen BE, Ohls JC, Ponza M, McCool AC. The Elderly Nutrition Program: an effective national framework for preventive nutritional interventions. J Am Diet Assoc. 2002;102(2):234-240.

16. Couderc AL, Camalet J, Schneider S, et al. Cobalamin deficiency in the elderly: aetiology and management: a study of 125 patients in a geriatric hospital. J Nutr Health Aging. 2015;19(2):234-239.

17. Wong CW. Vitamin B12 deficiency in the elderly: is it worth screening? Hong Kong Med J. 2015;21(2):155-164.

18. Allen LH. How common is vitamin B-12 deficiency? Am J Clin Nutr. 2009;89(2):693S-696S.

19. Karanth VK, Karanth L, Karanth TK, Karanth SK, Bekur R. A novel screening tool (Karanth's test) for vitamin B12 deficiency: a pilot study. BMC Res Notes. 2015;8:778.

20. Wild DB. The Skin, Tongue and Nails Speak: Observational Signs of Nutritional Deficiencies. Loveland, CO: Unique Perspective Press; 2013.

21. Chernoff R. Geriatric Nutrition: The Health Professional's Handbook. 4th ed. Burlington, MA: Jones & Bartlett Learning; 2014:55-57, 317-318.

22. Brouwer-Brolsma EM, Dhonukshe-Rutten RA, van Wijngaarden JP, Zwaluw NL, Velde Nv, de Groot LC. Dietary sources of vitamin B-12 and their association with vitamin B-12 status markers in healthy older adults in the B-PROOF study. Nutrients. 2015;7(9):7781-7797.

23. Harrington DJ. Laboratory assessment of vitamin B12 status. J Clin Pathol. 2017;70(2):168-173.