Latest Review Date: January 2024

Category:  Laboratory

POLICY:

Functional Intracellular Analysis (FIA), intracellular micronutrient panel testing, and all other live blood cell testing of intracellular nutritional status is considered investigational.

DESCRIPTION OF PROCEDURE OR SERVICE:

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 U. S.; 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. Also, some commercial laboratories offer panels of vitamin and mineral testing that also use serum analysis.

Diagnostic Testing

This evidence review evaluates laboratory tests that measures 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 compared with serum levels, because intracellular levels are not influenced by recent nutrition intake. However, the relationship between serum and intracellular levels of micronutrients is complex. The balance of intracellular and extracellular levels depend on a number of factors, including the physiology of cellular transport mechanisms and the individual cell type.

At least two commercial laboratories offer intracellular testing for micronutrients. Laboratories perform a panel of tests evaluating the intracellular level of a variety of micronutrients (e.g. minerals, vitamins, amino acids, fatty acids). The test offered by IntraCellular Diagnostics (EXA Test®) evaluates epithelial cells from buccal swabs and assesses levels of intracellular mineral electrolyte (i.e., magnesium, calcium, potassium, phosphorus, sodium, and 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: Vitamins A, B1, B2, B3, B6, B12, C, D, K; biotin, folate, pantothenic acid
• Minerals: calcium, magnesium, manganese, zinc, copper
• Antioxidants: α-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 may include SPECTROX™ for evaluation of the total antioxidant function and IMMUNIDEX™ for immune response score.

KEY POINTS:

The most recent literature review was updated through November 20, 2023.

Summary of Evidence

For individuals who have chronic diseases or nonspecific generalized symptoms who receive intracellular micronutrient analysis, the evidence includes an observational study. Relevant outcomes are symptoms, and change in disease status. No studies were identified that evaluated the 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 comparative studies were identified that evaluated the direct health impact of intracellular micronutrient testing. Moreover, there are not sufficient 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 that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

No practice guidelines or position statements were identified.

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Functional intracellular analysis (FIA), essential metabolic analysis, micronutrient testing, comprehensive nutritional panel, SpectraCell, IntraCellular Diagnostics, SpectraCell’s micronutrient test, IntraCellular Diagnostics ExaTest, intracellular micronutrient analysis,  SPECTROX®, bostonheart diagnostic®, Fatty Acid Balance test, IMMUNIDEX™

APPROVED BY GOVERNING BODIES:

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 panel testing is offered by SpectraCell Laboratories and IntraCellular Diagnostics under the auspices of the Clinical Laboratory Improvement Amendments. 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.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING: 

CPT Codes:

There is no specific CPT code for this panel of testing. Some of the elements of this testing might be reported with the codes below:

REFERENCES:

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 2010; 49(3):165-83.
2. IntraCellular Diagnostics. Mitochondria: Exploration of Intracellular Space.www.exatest.com/
3. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
4. SpectraCell Laboratories. Micronutrient Test. spectracell.sitewrench.com/search-tests

POLICY HISTORY:

Medical Policy Group, August 2009 (3)

Medical Policy Administration Committee, August 2009

Available for comment August 21-October 5, 2009

Medical Policy Group, August 2010 (1): New key words added, no coverage change

Medial Policy Panel, July 2011

Medical Policy Group, August 2011 (2): Title change, Description change, Addition to coverage policy statement, Update to Key Points, Key Words, Government Approval, References.

Medical Policy Administration Committee, August 2011

Available for comment August 11 – September 26, 2011

Medical Policy Panel, July 2012

Medical Policy Group, September 2012 (2): Key Points updated.

Medical Policy Group, January 2012 (2): Description, Key Points & References updated; policy statement remains unchanged

Medical Policy Panel, July 2013

Medical Policy Group, September 2013 (1): Policy updated with literature search through July 2013; no change to policy statement

Medical Policy Panel, July 2014

Medical Policy Group, July 2014, (1): Policy updated with literature search through June 2014; no change to policy statement

Medical Policy Panel, July 2015

Medical Policy Group, July 2015 (3): 2015 updates to Key Points and Benefit Application, no change to policy statement.

Medical Policy Group, August 2015 (3):  added bostonheart diagnostics® and fatty acid balance test to Key Words

Medical Policy Panel, March 2017

Medical Policy Group, March 2017 (3): 2017 Updates to Key Points, Key Words & Coding Section, no References added; No change to policy statement.

Medical Policy Panel, March 2018

Medical Policy Group, March 2018 (4): Updates to Description and Key Points. No change to policy statement.

Medical Policy Panel, December 2018

Medical Policy Group, January 2019 (9): 2018 Updates to Description & Key Points. No change to policy statement.

Medical Policy Panel, December 2019

Medical Policy Group, December 2019 (9): 2019 Updates to Description, Key Points. No change to policy statement. Placed Current CPT Codes into table for ease of reading, no changes to codes.

Medical Policy Panel, December 2020

Medical Policy Group, December 2020 (9): 2020 Updates to Description, Key Points. No references added. No change to policy statement.

Medical Policy Panel, December 2021

Medical Policy Group, December 2021 (9): 2021 Updates to Description, Key Points, References. Policy statement updated to remove “not medically necessary,” no change to policy intent. Key Word added: IMMUNIDEX™

Medical Policy Panel, December 2022

Medical Policy Group, December 2022 (9): 2022 Updates to Description, Key Points, References. No change to policy statement.

Medical Policy Panel, December 2023

Medical Policy Group, January 2024 (5): Updates to Key Points and Benefit Application. No change to Policy Statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.