Medical Policy Medical Policy
Policy Num: 11.001.039
Policy Name: Nutrient/Nutritional Panel Testing
Policy ID: [11.001.039] [Ac / B / M- / P-] [2.04.136]
Last Review: January 15, 2025
Next Review: January 20, 2026
Related Policies:
11.001.022 - Homocysteine Testing in the Screening, Diagnosis, and Management of Cardiovascular Disease and Venous Thromboembolic Disorders
11.001.037 - Intracellular Micronutrient Analysis
| Population Reference No. | Populations | Interventions | Comparators | Outcomes |
| 1 | Individuals: · With mood disorders, fibromyalgia, or unexplained fatigue, or healthy individuals who seek to optimize health and fitness | Interventions of interest are: · Nutritional panel testing | Comparators of interest are: · Standard of care | Relevant outcomes include: · Symptoms · Change in disease status · Functional outcomes |
Multimarker nutritional panel testing is proposed for patients with certain chronic conditions (eg, mood disorders, fibromyalgia, unexplained fatigue) as well as for healthy individuals seeking to optimize health and/or fitness.
For individuals who have mood disorders, fibromyalgia, or unexplained fatigue, or healthy individuals who seek to optimize health and fitness who receive nutritional panel testing, the evidence includes several systematic reviews and randomized controlled trials (RCTs) on the association between a single condition and a single nutrient and on the treatment of specific conditions with nutritional supplements. Relevant outcomes are symptoms, change in disease status, and functional outcomes. Systematic reviews have found statistically significant associations between depression or fibromyalgia and levels of several nutrients; however, there is little evidence that nutrient supplementation for patients with depression improves health outcomes. An RCT has also found statistically significant associations between fatigue and levels of vitamin D. However, there is no direct evidence on the health benefits of nutritional panel testing for any condition, including testing healthy individuals, and no evidence that nutritional panel testing is superior to testing for individual nutrients for any condition. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
Not applicable
The objective of this evidence review is to determine whether nutrient/nutritional panel testing improves the net health outcome among patients with mood disorders, fibromyalgia, or unexplained fatigue, or among healthy individuals seeking to optimize health and fitness.
Nutrient/nutritional panel testing is considered investigational for all indications including but not limited to testing for nutritional deficiencies in patients with mood disorders, fibromyalgia, unexplained fatigue, and healthy individuals.
See the Codes table for details.
BlueCard/National Account Issues
State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity.
Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.
Nutritional panel testing aims to identify nutritional deficiencies that will lead to personalized nutritional supplement recommendations. Testing is proposed both for healthy individuals to optimize health and for patients with chronic conditions (eg, mood disorders, fibromyalgia, unexplained fatigue) to specify supplements that will ameliorate symptoms.
Genova Diagnostics offers nutritional/nutrient panel testing. Among the tests this company offers is NutrEval® FMV, which involves analysis of urine and blood samples and provides information on more than 100 markers including organic acids, amino acids, fatty acids, markers of oxidative stress (direct measurement of glutathione and CoQ10, and markers of oxidative injury and DNA damage) and nutrient elements (Table 1).1,Genova Diagnostics produces a report that includes test results categorized as minimal, moderate, or high need for support, along with recommendations for supplements and dosages for items categorized as high need. NutrEval FMV patient reports can recommend supplementation for any of the nutrients listed in Table 1 if they are found to be areas of high need.
NutrEval Plasma, also by Genova Diagnostics, is a similar test.2, The only difference between NutrEval FMV and NutrEval Plasma is that the former uses urine (first morning void) whereas the latter uses plasma (fasting sample) to measure amino acids.
SpectraCell Laboratories offers a micronutrient test that measures functional deficiencies at the cellular level.3, The test assesses how well the body uses 31 vitamins, minerals, amino and fatty acids, antioxidants, and metabolites (see Table 1). SpectraCell categorizes test results into adequate, borderline, and deficient, and offers supplementation suggestions based on each patient’s deficiencies.
| Category | NutrEval FMV | Spectra Cell Nutrient Testing |
| Vitamins and antioxidants | Vitamin A, vitamin C, vitamin E, alpha-lipoic acid, coenzyme Q10, glutathione, plant-based antioxidants, B vitamins (t hiamin B1, riboflavin B2, niacin B3, pyridoxine B6, biotin B7, folic acid B9, cobalamin B12) | Vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, biotin, folate, pantothenate, vitamin C, vitamin D, vitamin K, alpha-lipoic acid, coenzyme Q10, cysteine, glutathione, selenium, vitamin E |
| Minerals | Magnesium, manganese, molybdenum, zinc | Calcium, magnesium, manganese, zinc, copper |
| Fatty acids | Omega-3-oils | |
| Digestive support | Probiotics, pancreatic enzymes | |
| Other vitamins | Vitamin D | |
| Amino acids | Arginine, asparagine, cysteine, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, serine, taurine, threonine, tryptophan, tyrosine, valine | Asparagine, glutamine, serine |
| Metabolites | Choline, inositol, carnitine |
Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments. Nutrient/nutritional panel testing using urine and/or blood samples is offered (eg, NutrEval FMV® and NutrEval Plasma® by Genova Diagnostics; micronutrient testing by SpectraCell) under the auspices of the Clinical Laboratory Improvement Amendments. Laboratories that offer laboratory-developed tests must be licensed by the Clinical Laboratory Improvement Amendments 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 evidence review was created in August 2015 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through October 16, 2024.
Evidence reviews assess whether a medical test is clinically useful. A useful test provides information to make a clinical management decision that improves the net health outcome. That is, the balance of benefits and harms is better when the test is used to manage the condition than when another test or no test is used to manage the condition.
The first step in assessing a medical test is to formulate the clinical context and purpose of the test. The test must be technically reliable, clinically valid, and clinically useful for that purpose. Evidence reviews assess the evidence on whether a test is clinically valid and clinically useful. Technical reliability is outside the scope of these reviews, and credible information on technical reliability is available from other sources.
Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.
The purpose of nutrient/nutritional panel testing in individuals who have mood disorders, fibromyalgia, or unexplained fatigue or in healthy individuals seeking to optimize health and fitness is to inform a decision on whether the patient might benefit from specific nutrient supplementation.
The following PICO was used to select literature to inform this review.
The relevant populations of interest are individuals with mood disorders, fibromyalgia, or unexplained fatigue, or healthy individuals seeking to optimize health and fitness.
The relevant intervention of interest is nutrient/nutritional panel testing.
The following practice is currently being used to manage mood disorders, fibromyalgia, unexplained fatigue, or healthy individuals seeking to optimize health and fitness: standard of care.
The potential beneficial outcomes of primary interest are an improvement in symptoms, change in disease status, and functional outcomes. The potential harmful outcomes are those resulting from a false test result. False-positive or false-negative test results can lead to the initiation of unnecessary treatment and adverse events from overtreatment or undertreatment.
Nutrient/nutritional panel testing might be conducted before or after starting specific therapy for the specific conditions addressed herein or as a screening test for healthy individuals seeking to optimize health and fitness.
For the evaluation of clinical validity of the nutrient/nutritional panel testing, studies that meet the following eligibility criteria were considered:
Reported on the accuracy of the marketed version of the technology (including any algorithms used to calculate scores).
Included a suitable reference standard.
Patient/sample clinical characteristics were described.
Patient/sample selection criteria were described.
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).
No studies on the sensitivity and specificity of nutrient/nutritional panel testing compared with a reference standard were identified.
A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing.
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from randomized controlled trials (RCTs).
No RCTs were identified that assessed the clinical utility of nutrient/nutritional panel testing for mood disorders, fibromyalgia, unexplained fatigue, or optimization of health and fitness.
Indirect evidence on clinical utility rests on clinical validity. If the evidence is insufficient to demonstrate test performance, no inferences can be made about clinical utility.
The chain of evidence to support the clinical utility of the use of nutrient/nutritional panel testing would consist of: (1) evidence that specific nutritional deficiencies included in the panel test are significantly associated with mood disorders, fibromyalgia, and/or unexplained fatigue; (2) evidence that, in patients with mood disorders, fibromyalgia, and/or unexplained fatigue, treatment of a patient found to have specific nutritional deficiencies (eg, with nutritional supplements) improves health outcomes; and (3) evidence that, if there is sufficient evidence on the first 2 items, panel testing is more appropriate than testing for specific nutrients.
Several systematic reviews and meta-analyses evaluating associations between the indications of interest (depression, fibromyalgia) and specific nutrient deficiencies were identified, and they are described in Table 2. No systematic reviews or meta-analyses were identified in the association between nutritional deficiencies and unexplained fatigue. A limitation of all reviews is that, although they compared low and high levels of nutrient levels, none addressed whether these low levels constituted actual deficiencies in a particular nutrient.
| Study | Nutrient | No. of Studies | Specified Cutoff for Nutrient Deficiency | Key Findings (95% CI) | |
| Depression | |||||
| Petridou et al (2015)4, | Folate and vitamin B12 | 11 | No | Odds of having depression significantly associated with low folate and vitamin B levels:
| |
| Cheungpasitporn et al (2015)5, | Magnesium | 6 | No | Pooled RR of depression in patients with hypomagnesemia (3 cohort studies, 2 cross-sectional studies, 1 case-control study combined; N=19,137 patients):
| |
| Swardfager et al (2013)6, | Zinc | 17 | No | Mean serum zinc concentrations of -1.85 μmol/L (-2.52 to -1.19 μmol/L) in depressed patients vs. nondepressed controls (p<.001) | |
| Anglin et al (2013)7, | Vitamin D | 14 | No | Cross-sectional studies:
| |
| Fibromyalgia | |||||
| Hsiao et al (2015)8, | Vitamin D | 12 | No | Significantly higher odds of hypovitaminosis D among patients with chronic pain including fibromyalgia vs. control group:
| |
| Daniel and Pitotta (2011)9, | Vitamin D | No | No pooled analyses. Lower-quality studies tended to find positive associations between fibromyalgia and low vitamin D levels; studies with control groups found no significant associations; larger population-based studies had mixed findings | ||
Evidence from multiple systematic reviews and meta-analyses of observational studies have indicated an association between deficiency of nutrients (vitamin B12, vitamin D, folate, magnesium, zinc) and different outcomes (depression, fibromyalgia). There is no evidence whether screening for these nutrient deficiencies results in improved health outcomes compared with no screening.
Two systematic reviews evaluating health outcomes in patients with depression treated with nutritional supplementation were identified, and they are described in Table 3. A limitation of these reviews is that they did not require patients to have an established deficiency of any nutrient. No systematic reviews or meta-analyses were identified on nutritional interventions in patients with fibromyalgia or unexplained fatigue.
| Study | Intervention and Comparator | No. and Type of Studies | Patients Diagnosed With Nutritional Deficiencies | Key Findings (95% CI) |
| Depression | ||||
| Gowda et al (2015)10, | Vitamin D (alone or combined with other vitamins or antidepressants) vs. placebo | 9 RCTs |
|
|
| Taylor et al (2003)11, | Folic acid (alone or as adjunctive treatment) vs. antidepressant medication | 3 RCTs | No |
|
Nowak et al (2016) conducted a single-center, double-blind, placebo-controlled trial to determine whether a single vitamin D dose would reduce fatigue after 30 days among 120 otherwise healthy persons with low serum 25-hydroxyvitamin D levels (mean age, 29 years; 53% women).12, The outcome was measured using the Fatigue Assessment Scale. The vitamin D group had a significantly greater decrease in mean (standard deviation) Fatigue Assessment Scale score (-3.3, standard deviation=5.3) than the placebo group (-0.8, standard deviation=5.3; p=.01). Improvements were reported more frequently in the vitamin D group (42 [72%]) than in placebo group (31 [50%]; p=.01; odds ratio, 2.63; 95% confidence interval for odds ratio, 1.23 to 5.62). Among all participants, improvement in the Fatigue Assessment Scale correlated with the rise in 25-hydroxyvitamin D levels (r=0.22, p=.02).
A systematic review of RCTs has suggested that folate might have a role as a supplement to other therapies in patients with depression. However, it is unclear whether folate supplementation would benefit both people with normal folate levels and those with folate deficiency. A meta-analysis of RCTs has suggested no significant benefit of vitamin D supplementation versus placebo in the case of depression. An RCT reported decreased fatigue in patients receiving a single dose of vitamin D, and suggested improvements in fatigue with vitamin D supplementation. There is no evidence whether screening for these nutrient deficiencies (versus no screening) would result in significant improvement in outcomes.
There is no evidence on any indication to suggest that nutritional panel testing improves the net health outcome compared with testing for 1 or several individual nutrients. This applies to patients with mood disorders, fibromyalgia, and/or unexplained fatigue, as well as healthy individuals seeking to optimize health and/or fitness. Moreover, with nutritional panel testing, there is a potential for incidental findings that could cause harm. Examples of potential harms include unnecessary confirmatory tests, unnecessary treatments provided for clinically insignificant conditions, toxicity related to supplementation, and interactions between nutritional supplements and prescription medications.
For individuals who have mood disorders, fibromyalgia, or unexplained fatigue, or healthy individuals who seek to optimize health and fitness who receive nutritional panel testing, the evidence includes several systematic reviews and randomized controlled trials (RCTs) on the association between a single condition and a single nutrient and on the treatment of specific conditions with nutritional supplements. Relevant outcomes are symptoms, change in disease status, and functional outcomes. Systematic reviews have found statistically significant associations between depression or fibromyalgia and levels of several nutrients; however, there is little evidence that nutrient supplementation for patients with depression improves health outcomes. An RCT has also found statistically significant associations between fatigue and levels of vitamin D. However, there is no direct evidence on the health benefits of nutritional panel testing for any condition, including testing healthy individuals, and no evidence that nutritional panel testing is superior to testing for individual nutrients for any condition. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
| Population Reference No. 1 Policy Statement | [ ] Medically Necessary | [X] Investigational |
The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.
Guidelines or position statements will be considered for inclusion in ‘Supplemental Information' if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest. No guidelines or statements were identified.
The U.S. Preventive Services Task Force (USPSTF) has not addressed nutritional panel testing. The USPSTF has made several recommendations addressing screening for individual nutrients. The USPSTF concluded that there is insufficient evidence to recommend for or against screening for iron deficiency anemia in asymptomatic children, adolescents and pregnant women, as well as vitamin D deficiency in asymptomatic, nonpregnant adults.13,14,15,
There is no national coverage determination. In the absence of a national coverage determination, coverage decisions are left to the discretion of local Medicare carriers.
A search of ClinicalTrials.gov in October 2024 did not identify any ongoing or unpublished trials that would likely influence this review.
| Codes | Number | Description |
|---|---|---|
| CPT | No specific code. Individual CPT codes would be used. Examples below: | |
| 82746 | Folic acid; serum | |
| 83735 | Magnesium | |
| 83785 | Manganese | |
| 84590 | Vitamin A | |
| 84630 | Zinc | |
| 82128 | Amino acids; multiple, qualitative, each specimen | |
| 82136 | Amino acids, 2 to 5 amino acids, quantitative, each specimen | |
| HCPCS | No Code | |
| ICD-10-CM | Investigational for all indications | |
| F30.10-F39 | Mood [affective] disorders code range | |
| M79.7 | Fibromyalgia | |
| R53.81-R53.83 | Other malaise and fatigue code range | |
| ICD-10-PCS | Not applicable. ICD-10-PCS codes are only used for inpatient services. There are no ICD procedure codes for laboratory tests. | |
| Type of service | Laboratory | |
| Place of service | Outpatient |
| Date | Action | Description |
|---|---|---|
| 01/15/2025 | Annual Review | Policy updated with literature review through October 16, 2024; no references added. Policy statement unchanged. |
| 01/08/2024 | Annual Review | Policy updated with literature review through October 23, 2023; no references added. Policy statement unchanged. |
| 01/03/2023 | Annual review | Policy updated with literature review through October 19, 2022; reference added. Minor editorial refinements to policy statements; intent unchanged. |
| 01/12/2022 | Annual review | Policy updated with literature review through October 19, 2021; no references added, reference to USPSTF vitamin D recommendation updated. Policy statement unchanged. |
| 01/12/2021 | Annual review | Policy updated with a literature review through October 20, 2020; references added. Policy statement unchanged. |
| 01/14/2020 | Annual review | Policy updated with a literature review through October 14, 2019; no references added. Policy statement unchanged. |
| 01/21/2019 | Annual review | No changes |
| 12/13/2018 | Created | New policy |