Intracellular Micronutrient Analysis AHS – G2099

Description of Procedure or Service

Micronutrients are dietary components, often referred to as vitamins and minerals, which although only required by the body in small amounts, are vital to development, disease prevention, and wellbeing. Micronutrients are not produced in the body and must be derived from the diet (CDC, 2015; Life, 2012). Micronutrients include essential inorganic micronutrients, or trace elements, and essential organic micronutrients, or vitamins (Gidden & Shenkin, 2000).

***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician.

Policy

Intracellular Micronutrient Analysis is considered investigational. BCBSNC does not provide coverage for investigational services or procedures.

Benefits Application

This medical policy relates only to the services or supplies described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore member benefit language should be reviewed before applying the terms of this medical policy.

When Intracellular Micronutrient Analysis is covered

N/A

When Intracellular Micronutrient Analysis is not covered

Intracellular micronutrient panel testing is considered investigational for all applications.

Policy Guidelines

Background

Micronutrients, such as zinc, selenium, copper, and vitamins C, E, and B, are involved in various metabolic processes, either acting as catalysts or facilitating various enzymatic functions. Micronutrient deficiency can result from pre-existing malnutrition, severity of current illness, and adverse effects of therapeutic regimens or procedures (Preiser et al., 2015). According to the Environmental Working Group (2017), common nutrient deficiencies in the United States include vitamin D, vitamin E, magnesium, calcium, vitamin A and vitamin C.

Measurement of serum levels of several vitamins is widely available via several commercial testing companies. However, blood concentrations of many nutrients, especially those involved in regulatory mechanisms such as calcium, zinc, and retinol, are maintained within narrow ranges regardless of body stores(Ross, Taylor, Yaktine, & Del Valle, 2011). Changes in blood concentrations of such nutrients only occur in progressed/severe deficiency states. In other cases, like for carotenoids, they can vary markedly because of a short half-life and depending on recent intake (Al-Delaimy et al., 2004). Moreover, conditions such as acute infections or stress can influence serum concentrations of some nutrients, such as zinc (Ryu, Langkamp-Henken, Chang, Shankar, & Cousins, 2011). Concentrations in other tissues, such as cell membranes, fat tissue, or bone, fluctuate less, which gives a better view of long-term supply (Elmadfa & Meyer, 2014).

Intracellular micronutrient lymphocyte analysis was developed based on the premise that “The peripheral blood lymphocyte is an ideal system for metabolic studies because it is easily obtained, is a primary resting cell that can be activated to proliferate, and presumably reflects both the genetic makeup and biochemical environmental history of the individual at the time the cells were formed”(Frye, 2010). It is designed to determine the functional status of 19 nutrients by measuring lymphocyte growth responses to variations of a patented, chemically defined serumfree medium (Bucci, 1993). The authors conclude that it “provides a sensitive, specific, and accurate method of determining nutrient needs, requirements, or deficiencies for each individual”(Bucci, 1994). Houston (2010) published a small study demonstrating that “Replacement of the micronutrient deficiencies, as well as high-dose therapy of selected nutraceuticals in combination with optimal diet, exercise and weight management resulted in control of blood pressure to goal levels in 62% of the hypertensive population” and Frye (2010) published a second small study of 10 patients which found “Both men and women showed substantial overall improvement in their vitamins and mineral cellular storage balance”. However, neither finding has been validated in larger studies.

This testing is promoted to the public as a screening for nutrient deficiency and to tailor supplements to individual needs. Fairfield (2017) states these tests are unwarranted for these reasons:

• There is insufficient information about the optimum blood levels of vitamins, making it difficult to interpret subtle deficiency states.
• There is a lack of evidence that vitamin supplements prevent disease in many healthy adults with low blood levels of vitamins, apart from those with specific diets or medical conditions.

Applicable Federal Regulations

Intracellular micronutrient testing is offered by companies SpectraCell and IntraCellular Diagnostics, which have Clinical Laboratories Improvement Amendments (CLIA) accredited laboratories. SpectraCell’s micronutrient panel test and the IntraCellular Diagnostics ExaTest have not been through the FDA approval process.

Guidelines and Recommendations

No studies were identified that evaluated the accuracy or clinical utility of intracellular micronutrient testing compared to standard testing for vitamin or mineral levels. In addition, no controlled studies were identified that evaluated changes to patient management or health impact of intracellular micronutrient testing. Limited data are available on correlations between serum and intracellular micronutrient levels. Intracellular micronutrient analysis was not included in recent reviews on micronutrient analysis (Elmadfa & Meyer, 2014; Raghavan, Ashour, & Bailey, 2016). Hence, the testing is considered investigational.

No recommendations or practice guidelines recommending intracellular micronutrient testing were identified in a literature search.

Billing/Coding/Physician Documentation Information

This policy may apply to the following codes. Inclusion of a code in this section does not guarantee that it will be reimbursed. For further information on reimbursement guidelines, please see Administrative Policies on the Blue Cross Blue Shield of North Carolina web site at www.bcbsnc.com. They are listed in the Category Search on the Medical Policy search page.

Applicable service codes: 82128, 82136, 82180, 82310, 82379, 82495, 82525, 82607, 82652, 82725, 82746, 82978, 83735, 83785, 84207, 84252, 84255, 84425, 84446, 84590, 84591, 84597, 84630, 84999 86353, 88348

BCBSNC may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

Scientific Background and Reference Sources

Al-Delaimy, W. K., van Kappel, A. L., Ferrari, P., Slimani, N., Steghens, J. P., Bingham, S., . . . Riboli, E. (2004). Plasma levels of six carotenoids in nine European countries: report from the European Prospective Investigation into Cancer and Nutrition (EPIC). Public Health Nutr, 7(6), 713-722.

Bucci, L. R. (1993). A functional analytical technique for monitoring nutrient status and repletion. Am Clin Lab, 12(6), 8, 10.

Bucci, L. R. (1994). A functional analytical technique for monitoring nutrient status and repletion. Part 3: clinical experience. Am Clin Lab, 13(5), 10-11.

CDC. (2015). Micronutrient Facts | IMMPaCt | CDC. Retrieved from https://www.cdc.gov/immpact/micronutrients/

Elmadfa, I., & Meyer, A. L. (2014). Developing Suitable Methods of Nutritional Status Assessment: A Continuous Challenge123. Adv Nutr, 5(5), 590S-598S. doi:10.3945/an.113.005330

Frye, D. L. (2010). Micronutrient Optimization Storage Trial Using Customized Vitamin & Mineral Replacement Therapy Most 2010. Translational Biomedicine, 1(3).

Gidden, F., & Shenkin, A. (2000). Laboratory support of the clinical nutrition service. Clin Chem Lab Med, 38(8), 693-714. doi:10.1515/cclm.2000.100

Houston, M. C. (2010). The role of cellular micronutrient analysis, nutraceuticals, vitamins, antioxidants and minerals in the prevention and treatment of hypertension and cardiovascular disease. Ther Adv Cardiovasc Dis, 4(3), 165-183. doi:10.1177/1753944710368205

Life, S. a. (2012). Micronutrients, Macro Impact. In. Retrieved from http://www.sightandlife.org/fileadmin/data/Books/Micronutrients_Macro_Impact.pdf

Preiser, J. C., van Zanten, A. R., Berger, M. M., Biolo, G., Casaer, M. P., Doig, G. S., . . . Vincent, J. L. (2015). Metabolic and nutritional support of critically ill patients: consensus and controversies. Crit Care, 19, 35. doi:10.1186/s13054-015-0737-8

Raghavan, R., Ashour, F. S., & Bailey, R. (2016). A Review of Cutoffs for Nutritional Biomarkers12. Adv Nutr, 7(1), 112-120. doi:10.3945/an.115.009951

Ross, A., Taylor, C., Yaktine, A., & Del Valle, H. (2011). Dietary Reference Intakes for Vitamin, D. and Calcium. The National Academies Collection. doi:10.17226/13050

Ryu, M. S., Langkamp-Henken, B., Chang, S. M., Shankar, M. N., & Cousins, R. J. (2011). Genomic analysis, cytokine expression, and microRNA profiling reveal biomarkers of human dietary zinc depletion and homeostasis. Proc Natl Acad Sci U S A, 108(52), 20970-20975. doi:10.1073/pnas.1117207108

Policy Implementation/Update Information

1/1/2019 BCBSNC will not provide coverage for intracellular micronutrient panel testing because it is considered investigational for all applications. BCBSNC does not provide coverage for investigational services or procedures. Medical Director review 1/1/2019. Policy noticed 1/1/2019 for effective date 4/1/2019. (jd)