Medical Policies - Medicine

Intracellular Micronutrient Analysis


Effective Date:10-15-2017



Intracellular micronutrient analysis, also known as functional intracellular analysis or essential metabolic analysis is considered experimental, investigational and/or unproven.


Commercial laboratories offer panels of tests evaluating intracellular levels of micronutrients (essential vitamins and minerals). Potential uses of these tests include screening for nutritional deficiencies in healthy people or those with chronic disease and aiding in the diagnosis of disease in patients with nonspecific symptoms.

“Micronutrients” collectively refer to essential vitamins and minerals necessary in trace amounts for health. Clinical deficiency states (states occurring after prolonged consumption of a diet lacking the nutrient that is treated by adding the nutrient to the diet) have been reported for vitamins A, B1, B12, C, and D, selenium, and other micronutrients. Classic nutritional deficiency diseases are uncommon in the United States; most people derive sufficient nutrition from their diets alone or in combination with over-the-counter multivitamins.

Laboratory tests are available for individual micronutrients and are generally used to confirm suspected micronutrient deficiencies. Testing is performed by serum analysis using standardized values for defining normal and deficient states. In addition, some commercial laboratories offer panels of vitamin and mineral testing that also use serum analysis.

This medical policy addresses laboratory tests that measure the intracellular levels of micronutrients. This testing, also known as intracellular micronutrient analysis, micronutrient testing, or functional intracellular analysis, is sometimes claimed to be superior to serum testing because intracellular levels reflect more stable micronutrient levels over longer time periods than serum levels, because intracellular levels are not influenced by recent nutrition intake. However, the relation between serum and intracellular levels of micronutrients is complex. The balance of intra- and extracellular levels depend on a number of factors, including the physiology of cellular transport mechanisms and the individual cell type.

At least 2 commercial laboratories offer intracellular testing for micronutrients. Laboratories perform a panel of tests evaluating the intracellular level of various micronutrients (e.g., minerals, vitamins, amino acids, fatty acids). The test offered by IntraCellular Diagnostics evaluates epithelial cells from buccal swabs and assesses levels of intracellular mineral electrolyte (i.e., magnesium, calcium, potassium, phosphorous, sodium, chloride). SpectraCell Laboratories offers a panel of tests that evaluates the intracellular status of micronutrients within lymphocytes in blood samples. The micronutrients measured by the test include:

Vitamins: A, B1, B2, B3, B6, B12, C, D, K; biotin, folate, pantothenic acid;

Minerals: calcium, magnesium, zinc, copper;

Antioxidants: alpha-lipoic acid, coenzyme Q10, cysteine, glutathione, selenium, vitamin E;

Amino acids: asparagine, glutamine, serine;

Carbohydrate metabolism: chromium, fructose sensitivity, glucose-insulin metabolism;

Fatty acids: oleic acid;

Metabolites: choline, inositol, carnitine.

The SpectraCell micronutrient panel also evaluates total antioxidant function.

Regulatory Status

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Intracellular micronutrient testing, offered by SpectraCell and IntraCellular Diagnostics, is available under the auspices of CLIA. Laboratories that offer LDTs must be licensed by CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.


This medical policy was originally created in July 1993 and has been updated regularly with searches of the MEDLINE database. Most recently, the literature was reviewed through January 25, 2017. Following is a summary of the key literature to date.

Intracellular Micronutrient Analysis

Clinical Context and Test Purpose

The purpose of diagnostic testing of patients who have chronic diseases or nonspecific generalized symptoms is to identify micronutrient deficiencies, not indicated by specific signs and/or symptoms, that would inform management decisions and improve health outcomes.

The question addressed in this medical policy is: Does intracellular micronutrient analysis testing improve health outcomes in individuals with chronic diseases or nonspecific generalized symptoms?

The following PICOTS were used to select literature to inform this review.


The relevant populations of interest are patients with chronic diseases or nonspecific generalized symptoms.


Intracellular micronutrient analysis.


Serum testing for nutritional deficiencies or standard management without nutritional testing.


The general outcomes of interest are test accuracy, symptoms, and change in disease status.


Short- and long-term symptom improvement and change in disease status; the time frame will vary depending on the chronic disease affecting the patient.


Testing can be ordered in primary care or specialty setting.

Analytic Validity

No studies on analytic validity were identified.

Clinical Validity

No studies on the sensitivity and specificity of intracellular micronutrient analysis tests compared with a reference standard (e.g., serum testing) were identified.

Clinical Utility

o Direct Evidence

No studies were identified reporting on the clinical utility of intracellular micronutrient analysis. The ideal study would be a randomized controlled trial evaluating health outcomes in patients who did and did not undergo intracellular micronutrient testing.

o Chain of Evidence

Absent direct evidence, a chain of evidence to demonstrate improved outcomes would require data that intracellular micronutrient testing can identify individuals with micronutrient deficiencies who would not otherwise be identified, that treatments are available for these patients that would not otherwise be given, and that these treatments improve health outcomes.

An observational study by Houston (2010) provided some data relevant to a chain of evidence. The study described a single center’s experience with micronutrient testing in the management of hypertension. (1) A total of 3338 patients treated over 5 years received micronutrient testing. Among the 3338 patients, 671 (20%) were considered to have hypertension (defined as blood pressure >140/90 mm Hg). The author stated that there were differences in levels of many micronutrients in the hypertensive versus nonhypertensive populations but did not report the specific micronutrients for which levels differed. Hypertensive patients identified as having micronutrient deficiencies were treated with high-dose therapy of appropriate supplements, as well as with recommendations on optimal diet, exercise, and weight management. The author reported that, after 6 months, 62% of the hypertensive population had succeeded in reaching their blood pressure goals and had tapered and discontinued hypertensive medication. The article did not report micronutrient levels before or after treatment and did not report 6-month blood pressure data for a comparison group of hypertensive patients who did not undergo micronutrient testing.

Section Summary: Clinical Utility

There is no direct evidence that intracellular micronutrient analysis improves health outcomes in patients with chronic diseases or nonspecific generalized symptoms. Moreover, there are insufficient data to construct a chain of evidence that intracellular micronutrient testing would likely lead to identifying patients whose health outcomes would be improved compared with alternative approaches to patient management.

Summary of Evidence

For individuals who have chronic diseases or nonspecific generalized symptoms who receive intracellular micronutrient analysis, the evidence includes observational studies. Relevant outcomes are test accuracy, symptoms, and change in disease status. No studies were identified that evaluated the analytic validity, clinical validity, or clinical utility of intracellular micronutrient testing compared with standard testing for vitamin or mineral levels. Limited data from observational studies are available on correlations between serum and intracellular micronutrient levels. No randomized controlled trials or other comparative studies were identified evaluating the direct health impact of intracellular micronutrient testing. Moreover, there are insufficient data to construct a chain of evidence that intracellular micronutrient testing would likely lead to identifying patients whose health outcomes would be improved compared with alternative approaches to patient management. The evidence is insufficient to determine the effects of the technology on health outcomes.

Practice Guidelines and Position Statements

No guidelines or statements were identified.


Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.


There is no specific CPT code for this panel of testing.

The specific CPT codes for each of the elements of the panel would most likely be reported (e.g., 84590 for vitamin A, 82310 for calcium, 82725 for oleic acid, etc.) along with multiple units of not otherwise specified (i.e., 84591) or unlisted (i.e., 84999) codes for elements of the panel which don’t have specific codes.

According to SpectraCell Laboratories, their total antioxidant function testing (which they call SPECTROX®) is reported using CPT code 86353.

IntraCellular Diagnostics uses electron microscopy for which CPT code 88348 might be reported.


Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.


The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

84999, 86353



ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual

Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <>.


1. Houston MC. 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. Jun 2010; 4(3):165-183. PMID 20400494

2. Intracellular Micronutrient Analysis. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (March 2017) Medicine 2.04.73.

Policy History:

Date Reason
10/15/2017 Document updated with literature review. Coverage unchanged.
10/1/2016 Reviewed. No changes.
7/15/2015 Document updated with literature review. No coverage changes.
12/1/2014 Reviewed. No changes.
10/15/2013 Document updated with literature review. No coverage changes. Document completely revised. Title changed from “Functional Intracellular Analysis”.
5/1/2008 Policy reviewed without literature review; new review date only. This policy is no longer scheduled for routine literature review and update.
9/1/2006 Revised/updated entire document
3/30/2004 Revised/updated entire document
5/1/1996 Revised/updated entire document
7/1/1993 New medical document

Archived Document(s):

Title:Effective Date:End Date:
Intracellular Micronutrient Analysis04-01-202107-14-2022
Intracellular Micronutrient Analysis07-15-202003-31-2021
Intracellular Micronutrient Analysis04-15-201907-14-2020
Intracellular Micronutrient Analysis06-15-201804-14-2019
Intracellular Micronutrient Analysis10-15-201706-14-2018
Intracellular Micronutrient Analysis10-01-201610-14-2017
Intracellular Micronutrient Analysis07-15-201509-30-2016
Intracellular Micronutrient Analysis12-01-201407-14-2015
Intracellular Micronutrient Analysis10-15-201311-30-2014
Functional Intracellular Analysis05-01-200810-14-2013
Functional Intracellular Analysis09-01-200604-30-2008
Functional Intracellular Analysis03-30-200408-31-2006
Essential Metabolic Analysis (EMA)05-01-199603-29-2004
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