How to Test for Leaky Gut

How to Test for Leaky Gut

Have you heard the phrase “leaky gut” thrown around on the internet, but you’re not quite sure what it means?

Does it conjure up images of your intestines leaking out their contents, but you feel like that can’t be what everyone is talking about??

Don’t worry, it’s a little less dramatic (and a little more complicated) than that!

“Leaky gut” is actually a simpler term for “increased intestinal permeability” – a fairly common phenomenon associated with many chronic conditions (1).

In this article, we’ll provide a brief overview of what leaky gut is, why it occurs, and how medical professionals can actually test for it.


What Is Leaky Gut?

The proper scientific term for leaky gut is “increased intestinal permeability” or “intestinal hyperpermeability” (2).

When the gut is “leaky”, it allows molecules that are normally kept out (like larger food particles or endotoxins) to pass through the lining of the intestines and into the bloodstream.

To understand why this might happen, first, we need to explore a little bit about the anatomy and physiology of the small intestine. We’ve broken it down into simple terms below.


The Anatomy of the Small Intestinal Barrier

Cells that make up the lining of the small intestine (where we absorb the bulk of our nutrients) are called enterocytes.

They form a barrier between the lumen (inside cavity) of the intestines and the rest of the body (3).

Their purpose is to regulate the absorption of vital nutrients and prevent anything dangerous (like bacteria, undigested food particles, or toxic substances) from being absorbed into the bloodstream (3).

In a healthy gut, most molecules (about 90%) are absorbed THROUGH the enterocytes, processed as needed, and then passed on into the bloodstream (4).

This is called the “transcellular” pathway and is tightly regulated to keep out anything harmful (5).

However, some molecules, especially small polar molecules like water, can also pass between the intestinal cells directly into the bloodstream (5).

This is known as the paracellular pathway.

Understanding the Paracellular Pathway

Enterocytes are held together by connections known as tight-junctions, adherens junctions, and desmosomes (6).

Normally, the permeability between enterocytes is very low and not many molecules are allowed to pass.

However, the permeability of these junctions can be influenced by a variety of factors, including regulatory proteins, nutrients, inflammatory cytokines, and bacteria (7).

When these factors cause tight junctions to stay open for too long, substances that otherwise wouldn’t be allowed to cross the intestinal barrier are able to cross, which can trigger an inflammatory immune response (4, 8).

And ultimately, when our bodies are exposed to inflammation over a long period of time, we are more likely to develop a variety of chronic diseases (9, 10, 11).

Demonstration of Trans and Paracellular Transportation Pathways


Causes of Leaky Gut

Potential causes of leaky gut that are currently being investigated include:

  • Alcohol consumption (12, 13)
  • Food components and additives (14)
  • High-fat diets (15)
  • Infections in the gut (16, 17)
  • Inflammation (18)
  • NSAID use (19, 20)
  • SIBO (21)
  • Stress (22, 23)
  • Vitamin A, Vitamin D, or zinc deficiency (24, 25)

9 Potential Causes of Leaky Gut - Functional Nutrition Answers


Conditions Linked to Leaky Gut

There are many conditions associated with leaky gut, but it is still debated whether increased permeability is a cause or consequence of these conditions.

These are some of the conditions that have been associated with leaky gut:

  • Alcohol-related liver disease (25)
  • Alzheimer’s disease (26)
  • Ankylosing spondylitis (27)
  • Asthma (28)
  • Autism (29)
  • Celiac disease (30, 31)
  • Chronic fatigue syndrome (32)
  • Critical illness or trauma (33, 34)
  • Depression (35, 36)
  • Fibromyalgia (37)
  • Food allergies or sensitivities (38, 39)
  • Inflammatory bowel disease (40, 41)
  • Irritable bowel syndrome (42)
  • Multiple sclerosis (43, 44)
  • NASH (45, 46)
  • Obesity (47, 48)
  • Parkinson’s disease (49)
  • Polycystic ovary syndrome (50, 51)
  • Rheumatoid arthritis (52)
  • Type 1 diabetes (53, 54)

What Types of Tests Are Available?

There are a few different ways to measure intestinal permeability, so let’s review the most common methods below.

1. Differential Sugar Test (Lactulose & Mannitol Test)

The differential sugar test has been used since the 1970s and is still the most popular way to test intestinal permeability (55).

There are technically a variety of sugars that can be used in this test, but lactulose and mannitol are most common and will be the focus of this review.

How does it work?

To perform the test, a sweet solution containing lactulose and mannitol is consumed after an overnight fast.

Then, all excreted urine is collected for 6 hours in order to measure the amount of lactulose and mannitol it contains (56).

Lactulose is a larger sugar, so it is not normally absorbed whole. If lactulose is found in the urine, it is assumed to have passed between the cells, indicating a “leaky” gut (56).

In contrast, mannitol is a smaller sugar alcohol that can be absorbed through enterocytes, particularly via small pores at the top of the villi of the small intestine.

The purpose of including mannitol in the drink is two-fold:

  1. It controls for any extraneous factors that might affect absorption or excretion (like gut motility or kidney function) since those factors would affect both types of sugars equally (57, 58).
  2. It can detect villous atrophy in the small intestine, since mannitol is primarily absorbed there. Poor mannitol absorption and excretion (but normal or high lactulose) suggests probable damage to the small intestinal villi.

This test is typically performed at hospitals or clinics, but health practitioners can also order at-home test kits for patients. Genova Diagnostics is a popular choice for these home testing kits, as well as Doctor’s Data.

Interpreting the Results.

The test results are usually expressed as a lactulose-to-mannitol ratio (LMR), in which the percentages (compared to the original oral dose) of lactulose and mannitol present in the urine are compared to each other (LMR = %lactulose / %mannitol) (57).

A higher LMR is associated with increased gut permeability (aka leaky gut).

It is important to note that this test may not be accurate when someone has SIBO (small intestinal bacterial overgrowth) because bacteria in the small intestine can metabolize these sugars before they are absorbed (59).

This could lead to low levels of lactulose and mannitol in the urine and potentially false-negative results.

Is there evidence to support this test?

Numerous studies have shown that LMR correctly identifies increased intestinal permeability, especially in patients with gastrointestinal diseases like Celiac disease and Crohn’s disease (60, 61, 62, 63).

However, lactulose is still a relatively small molecule (molecular weight of 342 Da), so it may not actually be a good indicator for how larger food antigens or bacterial toxins (which usually have a molecular weight of 5,000+ Da) would pass through the gut (64).

It is also important to note that other areas of the digestive tract can also become “leaky”, but different types of molecules are used to test the permeability of those regions (sucrose for the stomach, sucralose for the colon, or PEG or EDTA for the whole tract) (2459).

The Verdict: The lactulose & mannitol urine test is a popular way to evaluate permeability of the small intestine and is backed by decades of research. However, it’s important to note that this test may not be accurate for people with SIBO.

2. Serum Zonulin Testing

Zonulin is a regulator protein that basically acts like a gatekeeper of the intestines.

When zonulin levels rise, the tight junctions between enterocytes open slightly in order to allow nutrients and other molecules to move between them (1).

Since the discovery of the regulatory protein zonulin in the year 2000, scientists have been measuring serum zonulin levels to determine the likelihood of increased intestinal permeability (30).

How does it work?

Testing for zonulin is a much simpler process than the differential sugar test.

If you choose to have this test done, your blood will be drawn and sent to a lab where it will be evaluated for the amount of zonulin it contains.

High levels of zonulin in the blood means too much zonulin has been released in the gut, which probably signifies increased permeability (1).

There are several labs that offer zonulin testing:

  • The “Advanced Intestinal Barrier” test from Dunwoody Labs evaluates serum zonulin, DAO, and histamine levels.
  • The popular “GI-Map” from Diagnostic Solutions Laboratory is a stool test designed to evaluate your gut microbiome. It also offers fecal zonulin as an add-on.

Is there evidence to support this type of test?

While many studies have found high zonulin levels in patients with conditions associated with leaky gut, there are a few issues with using this lab test as a way to diagnose leaky gut (3065, 66).

Problem #1: Unstable zonulin levels.

Zonulin levels are prone to large fluctuations because zonulin is targeted by the immune system.

Once released into the bloodstream, macrophages target and destroy zonulin, so blood levels will vary for each person from day to day, based on their immune response (67, 68).

Problem #2: Measurement error.

Another issue is that most labs use a technique called ELISA (enzyme-linked immunosorbent assay) to measure zonulin levels in blood samples.

However, a study released in 2018 found that ELISA often improperly identified other types of proteins as zonulin, leading to falsely elevated results (69).

Problem #3: Poor correlation with differential sugar tests.

In one study, researchers actually tested patients using both lactulose/mannitol and zonulin testing.

The results of the two tests didn’t correlate very well, so some scientists have questioned the usefulness of serum zonulin testing (65, 67).

Zonulin Antibodies – A better choice?

Testing for zonulin antibodies might be a better alternative.

A recent study found that zonulin antibody testing had better reproducibility (meaning that it consistently showed the same results for the same patient) than serum zonulin levels (67).

Basically, when zonulin is released into the bloodstream, it triggers certain immune cells to produce specific antibodies (also called immunoglobulins) that recognize zonulin.

Because these zonulin antibodies are more stable and remain in the bloodstream longer, they are thought to be a better measurement of zonulin release than serum zonulin  (70).

The Verdict: Testing for zonulin antibodies (through labs like Cyrex or Vibrant Wellness) is more accurate than testing serum zonulin alone. However, it’s unclear whether this is better than lactulose/mannitol testing.

3. Other Types of Antibody Testing

In addition to testing for zonulin antibodies, other types of antibodies are being used as indirect measures of gut permeability.

These include:

  • LPS antibodies: Lipopolysaccharide is a type of sugar found on the cell walls of some gram-negative bacteria. LPS molecules are released when the bacteria die, but since they are relatively large in size they do not normally pass through the lining of the small intestine. However, when the gut is “leaky” some LPS can pass between the cells and stimulate the immune system. Therefore, the presence of LPS antibodies in the blood is an indirect marker of gut permeability (71).
  • Occludin antibodies: Occludin is one of the proteins that make up the tight-junctions between enterocytes. If occludin breaks down, the gut becomes more permeable, and if occludin fragments cross the intestinal barrier, they can stimulate the immune system to form antibodies against them. The presence of occludin antibodies in the blood suggests leaky gut (72).
  • Actomyosin network antibodies: Similarly, actomyosin proteins are found between the cells of the small intestinal lining and play a role in opening up the tight junctions. If the actomyosin network begins to break down and antibodies are formed, it suggests increased gut permeability as well (72, 73).

Testing options:

  • Cyrex Labs has a test called “Array 2” that analyzes zonulin antibodies as well as antibodies for occludin and LPS.
  • Vibrant Wellness has a test called “Wheat Zoomer” that checks for zonulin, actin, and LPS antibodies and also includes serum zonulin levels.

It is important to note that any testing that involves antibodies can be blunted by steroids or immunosuppressants.

While these tests don’t directly measure intestinal permeability, if larger molecules like LPS are able to pass through the intestinal barrier and be flagged by the immune system, chances are that other large molecules like food antigens are able to pass through as well.

4. Intestinal Biopsy

Technically, the most direct way to test for leaky gut is to have an intestinal biopsy done (24).

After removing a sample of intestinal tissue, a device called an “Ussing chamber” is used to measure the transport of molecules across the lining of the intestines (74).

Using this information, it can be determined whether there is actually increased permeability.

Biopsy was the first method used when scientists began studying the concept of intestinal permeability. However, since this an expensive and invasive method, it is not typically used in clinical practice.

Instead, scientists used the information they learned from studying intestinal permeability to create less invasive tests, like the differential sugar test (75).

The Verdict: Intestinal biopsies for the evaluation of leaky gut may be accurate, but this method is far too invasive, expensive, and labor-intensive to be used regularly. It is typically only used in research settings.


Should You Get Tested for Leaky Gut?

Well…maybe not.

Many practitioners believe that testing for leaky gut is a waste of time and money for several reasons.

Downside #1: Leaky gut is probably pretty common.

We know that leaky gut is linked with MANY health conditions (see above), so if you have any of them, there’s a very good chance you have leaky gut as well.

Downside #2: It doesn’t get to the root cause.

Sure, testing for leaky gut can tell you whether or not you have increased intestinal permeability, but many practitioners believe that leaky gut is more of a symptom than a root cause.

Ultimately, we need to know what actually triggered the leaky gut so that we can address that directly.

That’s why many practitioners prefer to evaluate or test for things that are likely to trigger leaky gut, like infections, stress, nutrient deficiencies, or alcohol and medication use.

Downside #3: Knowing if you have leaky gut will probably not affect your treatment.

Knowing whether or not you have leaky gut will probably not affect your treatment protocol.

Testing for leaky gut doesn’t get you any closer to figuring out the root cause (which can then be addressed directly).

Someone on a limited budget is probably better off requesting more targeted tests to determine why their gut might be extra permeable.

However, some practitioners do like to test for leaky gut to evaluate the effectiveness of their interventions.

So, for example, if intestinal permeability is high at the beginning of treatment and then reduced after therapy, this suggests that the treatment protocol was probably effective.

If you do choose to get tested for leaky gut, the best options are the differential sugar test (lactulose/mannitol test) and zonulin antibody testing.


Final Thoughts

Leaky gut (or, more technically, intestinal hyperpermeability) is a real phenomenon associated with many health conditions.

It occurs when the tight junctions between the cells that line our small intestines open up slightly, allowing larger molecules to “leak” through into the bloodstream.

When the immune system encounters these unexpected molecules, it can trigger an inflammatory response, which over time, is believed to increase the risk of many chronic illnesses.

However, leaky gut is probably more of a symptom than a root cause. Digging deeper to find the things that trigger leaky gut may be a better use of time and resources.

Because of this, most healthcare practitioners don’t specifically test for leaky gut unless they plan to use it as a marker of treatment effectiveness.

If you do plan on testing for leaky gut, the differential sugar test or serum zonulin antibodies are the preferred methods.

Join the Functional Nutrition Library

How to Test for Leaky Gut - Functional Nutrition Answers
What Is the Best Vegan Omega-3 Supplement?

What Is the Best Vegan Omega-3 Supplement?

Fatty fish, like salmon, sardines, and mackerel are some of the best natural sources of omega-3 fatty acids (1).

Because of this, most people reach for fish oil supplements when they want to boost their omega-3 intakes.

But what about vegans and vegetarians? Are there good vegan supplement options available for them too?

To answer this question, let’s review the different types of omega-3 fatty acids and then discuss which vegan omega-3 supplements are best.


What Are the Different Types of Omega-3s?

There are many different types of omega-3s fatty acids, but only a few have been well-studied for their health benefits (1).

The three main ones are ALA, EPA, and DHA.

Let’s review each one in-depth to learn more.


1) Alpha-Linolenic Acid (ALA)

ALA is a “short-chain” omega-3 fatty acid, because it contains only 18 carbon atoms (2).

It is also an essential fatty acid, meaning that the body cannot make it and we must get it from food.

ALA is the main vegan omega-3 fatty acid, found mostly in plant foods.

Some of the best sources include:

  • Perilla Oil: 8820 mg ALA per tablespoon (3)
  • Flaxseed Oil: 7196 mg ALA per tablespoon (4)
  • Chia Seeds: 4915 mg ALA per ounce (5)
  • Echium Seed Oil: 3745 mg ALA per tablespoon (6)
  • Walnuts: 2565 mg ALA per ounce (7)
  • Ground Flaxseed: 1597 mg ALA per tablespoon (8)
  • Canola Oil: 1279 mg ALA per tablespoon (9)
  • Soybean Oil: 917 mg ALA per tablespoon (10)
  • Hemp Seeds: 868 mg ALA per tablespoon (11)  
  • Mustard Oil: 826 mg ALA per tablespoon (12)
  • Edamame: 555 mg ALA per cup (13)
  • Navy Beans: 322 mg ALA per cup, cooked (14)
  • Brussels Sprouts: 270 mg ALA per cup, cooked (15)
  • Cauliflower: 208 mg ALA per cup, cooked (16)
  • Broccoli: 186 mg ALA per cup, cooked (17)
  • Spinach: 166 mg ALA per cup, cooked (18)

As you can see, it is generally easy for vegans to get enough ALA in their diets. Just one serving of walnuts provides more than the average adult needs in a day (19).

But… eating ALA alone isn’t enough.

ALA is just one type of omega-3, but we also need the other two types, EPA & DHA.

Humans can convert ALA into EPA (which can then be converted into DHA), but not very effectively (20).

It is estimated that only 8 to 21% of ALA is converted to EPA, and 0 to 9% is converted to DHA (21, 22). Women appear to be roughly 2.5 times better at this conversion than men, perhaps due to hormonal differences (23, 24).

Sadly, this already poor conversion can be cut in half with a diet containing too many omega-6 fatty acids (which is typical of the Standard American Diet) (25, 26).

We actually know the genes involved in these conversions too (FADS1, FADS2, ELOVL1, ELOVL2), so genetic testing can tell you a little bit more about how well your body handles them (27, 28).

To get around the genetic variability and overall poor conversions between ALA, EPA, and DHA, many people choose to take EPA & DHA supplements. That way, you know exactly how much you are getting.

However, ALA still has some benefits!

While ALA does not appear to have the exact same health benefits as EPA and DHA, it is still a required nutrient in our diets (29).

Preliminary studies show that ALA may enhance heart health, protect against inflammation, and improve brain function, but more research is needed (30).

Since ALA is relatively abundant in foods, it is not commonly taken as a supplement.


2) Eicosapentaenoic Acid (EPA)

EPA is a “long-chain” omega-3 fatty acid, because it contains 20 carbon atoms (2).

EPA is found mainly in seafood, especially fatty fish like salmon, mackerel, sardines and roe (fish eggs/caviar). One cooked 3-oz wild salmon filet contains about 1,500 mg of EPA + DHA combined (31, 32).

Grass-fed meats are also “good” EPA sources (containing at least 30 mg of EPA + DHA per 100 grams), which is on par with the amounts found in some white fish, but still far less than fatty fish contain (33).

Grass-fed dairy and pasture-raised eggs contain even smaller amounts, but still serve as the main sources of EPA for some vegetarians (34).

Are there any vegan sources of EPA?

Unfortunately, there aren’t many plants that contain substantial amounts of EPA.

The main source is microalgae. However, since algae is relatively low-fat, it is not a very concentrated source.

To get around this, most people take algal oil supplements, which are highly purified sources of both EPA and DHA (35).

Microalgae is actually the original source of omega-3s in the marine food chain, which is why seafood is one of the best food sources of EPA and DHA (36).

You might also see krill oil available on the market, but krill are actually small marine animals and are not vegan.

Many omega-3 fortified food products are also available, but it is important to read the label to make sure they contain EPA and/or DHA, and not just ALA.

Reading the ingredients list will tell you whether a vegan source like algal oil was used.

What are the health benefits of EPA?

One of the main functions of EPA is to compete with omega-6 fatty acids for the production of eicosanoids, which can generally be either pro-inflammatory or anti-inflammatory (37, 38).

The eicosanoids made from omega-6 fatty acids tend to be pro-inflammatory, while those made from omega-3s tend to be anti-inflammatory (although there are some exceptions to this rule) (37, 39).

This is why people talk about the importance of having a good balance of omega-6 and omega-3 fatty acids in the diet. More omega-3s = more anti-inflammatory eicosanoids, while too many omega-6 fatty acids can spur inflammation.

Large doses of EPA (and DHA) also help lower triglyceride levels by simultaneously reducing triglyceride production and increasing triglyceride clearance (40).

This is why high doses of fish oil are often recommended for people with dyslipidemia (41).

Other health benefits associated with EPA (and DHA) include improved cardiovascular health and reduced symptoms of some mental health disorders (42, 43, 44, 45).


3) Docosahexaenoic acid (DHA)

DHA is also a “long-chain” omega-3 fatty acid, with 22 carbon atoms (2).

It can be made from EPA, but humans are not very good at this conversion. Because of this,  most people consume DHA through food and/or take supplements.

What are the food sources of DHA?

Food sources of DHA are generally the same as EPA. The highest amounts of DHA are found in fatty fish, but microalgae is a good vegan source as well (46).

What are the benefits of DHA?

DHA is excellent for vision and the nervous system.

It is especially good at increasing the fluidity of cell membranes and is found in the highest amounts in the brain and retina (47, 48).

It’s also found in really high concentrations in male sperm (49, 50).

Compounds known as neuroprotectins can be made from DHA, which are potent antioxidants that protect these important cells and tissues from oxidative damage (51, 52).

Like EPA, high doses of DHA can help lower triglyceride levels and reduce inflammation.

However, DHA tends to raise LDL cholesterol levels a little more than EPA (although whether this even matters is debatable) (35, 53).


3 main types of omega-3s - Functional Nutrition Answers


How Much Omega-3 Is Needed?

Recommendations vary based depending on why you’re interested in taking omega-3s.

For General Health

Of the three most common omega-3 fatty acids, only ALA has an official “Adequate Intake” of 1.1 grams per day for women and 1.6 grams per day for men (19).

An “Adequate Intake” (AI) is basically the amount of a nutrient that is ASSUMED to be adequate for overall health. This type of recommendation is made when there isn’t enough evidence to establish a “Recommended Daily Intake” (RDA).

In contrast, there are no official intake recommendations for EPA and DHA at this time.

However, health organizations around the world generally recommend getting 250-500 mg of EPA + DHA (combined amount) per day for optimal health (54, 55, 56).

For reference, the Academy of Nutrition and Dietetics officially recommends the higher dose of 500 mg EPA + DHA daily (57).

Instead of recommending a specific amount, some organizations simply suggest consuming fatty fish two times per week, since it is a natural source of these nutrients (58).

Unfortunately, most Americans are not meeting these recommendations and only get about 100 mg of EPA + DHA per day (59).

For Vegans and Vegetarians

Although it is known that vegans and vegetarians tend to have lower blood levels of EPA and DHA, there are no specific dosage recommendations other than the standard 250-500 mg per day (60, 61).

It is generally recommended that vegans and vegetarians meet their EPA and DHA needs by taking algal omega-3 supplements and consuming food sources of ALA (61, 62).

However, it’s important to note that there is currently no evidence that vegetarians and vegans consuming low amounts of DHA have any additional adverse health effects (60).

During Pregnancy & Breastfeeding

For women who are pregnant or breastfeeding, an additional 200 mg of DHA per day is recommended to encourage healthy brain, retina, and nervous system development (63, 64).

For Health Conditions

People with inflammatory conditions may benefit from even higher intakes of omega-3s.

The American Heart Association recommends 1,000 mg of EPA + DHA (combined) per day for people with a history of heart disease, taken under the guidance of a physician (65).

Doses from 2,000 to 16,200 mg per day have been used to lower triglycerides, reduce symptoms of arthritis, or improve mental health conditions like depression, anxiety, and ADHD (66, 67, 68, 69, 70)

However, there is some concern that using high-dose EPA or DHA as an anti-inflammatory may be more of a nutraceutical approach, simply blunting the inflammatory response without actually getting to the root cause of the inflammation (39).

The Importance of Vitamin E?

Fats are very sensitive to oxidation, and too many oxidized fats within the body can promote inflammation (71, 72).

Vitamin E is a major fat-soluble antioxidant within the body that helps prevent this oxidation.

Some researchers believe that people taking supplemental omega-3s may need additional vitamin E to prevent excessive oxidation, but there has been no real consensus in the literature (73, 74, 75, 76, 77).

How Much EPA + DHA Is Best? -FNA


Possible Downsides of High-Dose Supplementation

Studies suggest that using omega-3’s to reduce inflammation may not always be a good thing if that inflammation was acting in a protective manner (78).

For example, one study in mice found that giving high doses of omega-3’s reduced intestinal inflammation, but actually increased the risk of sepsis, because the inflammation was protecting against bacteria crossing into the bloodstream (79).

As always, you should speak with your doctor before beginning any new supplement regimen.


Do Vegan Omega-3 Supplements Work as Well as Fish Oil?

Although the research is limited, a few studies have shown that algal omega-3 supplements raise blood levels of DHA just as effectively as eating fish or taking fish oil supplements (80, 81, 82, 83).

To boost absorption, omega-3 supplements should be taken with meals, and preferably ones that contain fat (84).


How to Choose a Good Vegan Omega-3 Supplement

Here are some quick tips for choosing a good omega-3 supplement:

  • Look at EPA & DHA levels: A high-quality omega-3 supplement will indicate exactly how much EPA & DHA it contains per serving. If it does not specify, pick another option.
  • Check for quality: Omega-3s can oxidize and go rancid, so look for products stored in the refrigerated section or ones that contain natural antioxidants like rosemary to extend their shelf-life.
  • Toss it if it smells: If your supplement smells strongly fishy or gives you yucky-tasting burps, it may have gone rancid and should not be taken anymore.
  • Choose a triglyceride form: Omega-3’s naturally exist in triglyceride form in food, and most over the counter supplements are also in this form (although technically they have been purified and then re-formed into triglycerides to increase the proportion of EPA/DHA). Some high-dose prescription supplements come in ethyl ester form (similar to a monoglyceride, but with an ethanol backbone) or as free fatty acids, but some studies show that these are not as well absorbed or utilized by the body (84, 85, 86, 87).

If you are not sure whether you would benefit from an omega-3 supplement, you could consider testing your EPA & DHA levels first.

The HS-Omega-3 Index, which measures red blood cell membrane levels of EPA and DHA, is considered to be a good long-term indicator of fatty acid status over the last few months (88, 89, 90).

This is generally considered to be a more helpful measure than plasma levels, since blood levels of EPA & DHA don’t necessarily reflect tissue levels (91, 92).

If you do plan on starting an omega-3 supplement, be aware that it can take up to 2 weeks to see differences in EPA levels and up to 1 month to see differences in DHA levels on this test (93).

How to Choose a Good Omega-3 Supplement - FNA


The Best Vegan Omega-3 Supplements

There are hundreds of vegan omega-3 supplements to choose from, so we’ve narrowed it down to two options from our favorite brand.

Both varieties contain a combined total of at least 500 mg EPA + DHA per serving, at least 200 mg of DHA, and are lab-verified to be high-quality.

Please note that as an Amazon Associate I earn from qualifying purchases.

1. Nordic Naturals Algae Omega (Softgel)

A soft gel form of algal omega-3 is also available from Nordic Naturals. It contains 390 mg DHA and 195 mg EPA per serving (which is 2 softgels).

Labdoor did an independent analysis on this supplement and rated it a 97.9/100 for overall quality.

When tested, it actually contained slightly more EPA & DHA than claimed on the label and was within the California Prop 65 limits for heavy metal contamination and had not gone rancid.

This is an especially good option because it is affordable and easily found in grocery stores or bought online here.

2. Nordic Naturals Algae Omega (Liquid)

This lemon-flavored liquid omega-3 supplement from Nordic Naturals contains 350 mg DHA and 200 mg EPA per serving (1.5 mL).

This supplement is a great choice for anyone who cannot tolerate swallowing softgels or who would prefer to mix the oil into smoothies or shakes.

Like Nordic Natural softgels, this product is generally easy to find in stores and can be bought online here.


Safety & Side Effects

Safety of Omega-3 Supplementation

Omega-3 supplementation is generally considered to be low risk, especially at doses below 5 grams per day (94).

However, you should always consult with your physician before taking a new supplement.

This is especially true for people taking blood thinning medications, because some studies (but not all) have shown an increased risk of bleeding in people taking high doses of omega-3 supplements (95, 96, 97, 98, 99, 100).  

Your doctor can help you decide whether the benefits outweigh the risks and periodically monitor your bloodwork.

Possible Side Effects

Side effects of taking omega-3 supplements are usually mild, and may include stomach upset, heartburn, diarrhea, a bad taste in your mouth or smelly sweat (101, 102).

Spacing out your supplements into smaller doses throughout the day may help reduce these effects.

Supplementing with DHA may also increase LDL cholesterol levels, but this increase appears to be relatively small (only about 3%) for doses around 2,000 mg per day (94).

However, higher doses of the ethyl ester form of EPA + DHA found in prescription-strength supplements may increase LDL levels by up to 32% (94, 103).

This does not appear to happen with high dose EPA-only supplements, but more research is needed (103).


Final Thoughts

All three types of omega-3s are important, but evidence shows that EPA and DHA may have unique benefits, especially for reducing inflammation and boosting brain and retinal health.

Vegan foods, such as nuts and vegetable oils, contain large amounts of ALA, but EPA and DHA are mainly found in animal foods (fish and meat).

Because there are not many adequate vegan food sources of EPA and DHA, those who follow a vegan diet often have lower levels of these fatty acids in their blood. Though, it’s unclear whether these lower levels are harmful.

Algal oil supplements are often recommended as a low-risk option to increase vegan EPA and DHA intake.

There are no official recommendations for dosing, but most organizations suggest around 500 mg of EPA + DHA per day for general health.

Our preferred brand of vegan omega-3 supplements is Nordic Naturals, which can be found in most stores or online.

Join the Functional Nutrition Library

What Is The Best Vegan Omega-3 Supplement? - Functional Nutrition Answers
What Is the Best Food Sensitivity Test?

What Is the Best Food Sensitivity Test?

Do you suspect that you might be suffering from food sensitivities?

Have you been bombarded by advertisements for food sensitivity tests but aren’t sure which one to choose?

You’re not alone! There are dozens of tests to choose from, all claiming to be the best, so it’s important to do your research before you decide.

This article will differentiate food sensitivities from other types of adverse food reactions, provide an overview of common food sensitivity tests and the science behind them, and help you decide which test is best.

What Are Food Sensitivities?

A food sensitivity is a type of adverse food reaction – a term that basically encompasses all the different ways you could negatively react to a food.

There are three main types of adverse food reactions, and each has a very different biological pathway:

1) Food intolerances: Food intolerances do not involve the immune system (1, 2). They occur when the body lacks the digestive enzymes needed to break down certain foods. An example would be lactose intolerance, in which the body cannot break down the milk sugar lactose, causing bloating and diarrhea (3). Food intolerances can also occur due to direct pharmacological effects of chemicals, like histamine.

2) Food allergies: Food allergies DO involve the immune system. They occur when the body creates IgE antibodies to a food, which then trigger the release of histamine and other pro-inflammatory mediators from mast cells (located in your tissues) next time you eat that food (4). These reactions are typically rapid, occurring within minutes or hours (1). An example would be a peanut allergy that causes swelling, hives, and difficulty breathing.

3) Food sensitivities: Food sensitivities ALSO involve the immune system, but NOT IgE antibodies (4). Instead, they occur when circulating white blood cells (lymphocytes or granulocytes) react to a food or chemical and release pro-inflammatory chemicals known as “mediators” into the bloodstream, which cause symptoms throughout the body. These reactions are often delayed and dose-dependent (5). An example would be a wheat sensitivity that causes abdominal pain, diarrhea, and brain fog the day after eating a moderate amount of wheat (6).

Unfortunately, the medical community hasn’t come to a consensus on the exact definition of “food sensitivities,” so you’ll often hear the term used in many different (and confusing) ways (2).

Some people may refer to food sensitivities as “non-IgE food allergies,” others may classify them as different types of “food intolerances,” and still others call them “delayed hypersensitivity reactions.”

While the terminology might be used differently, the science behind it is the same.

Ultimately, when we use the term “food sensitivity,” we’re talking about any immune-mediated adverse food reaction that DOESN’T involve IgE (the antibody responsible for food allergies).

The Science Behind Food Sensitivities

In order to really evaluate the different food sensitivity tests available, it is important to understand a few things about the immune system.

Any time the immune system reacts inappropriately to a harmless substance (such as food), this is called a hypersensitivity reaction (7).

For food sensitivities (non-IgE-mediated reactions), there are two main pathways in which these reactions can occur (8):

  • Type III reactions, also known as immune-complex reactions, occur when IgG, IgM, or IgA antibodies bind to a food antigen and trigger white blood cells to release mediators, which causes symptoms (7, 9).
  • Type IV reactions, also known as cell-mediated reactions, occur when white blood cells (lymphocytes or granulocytes) are independently triggered to release mediators, without the involvement of antibodies (7, 10, 11).

It is important to understand that food sensitivities can be caused by both type III and type IV reactions (plus others, like cytotoxic reactions caused by chemicals, which do not neatly fit into any of these categories).

So, if you are looking for a food sensitivity test, you want one that will measure ALL types of possible pathways.

No matter which type of reaction is occurring, the end result is that mediators are released by your white blood cells (812, 13).

These mediators can cause a variety of symptoms, depending on which types are released:

  • Proinflammatory mediators will cause inflammation (acute or delayed) or suppress anti-inflammatory pathways (14).
  • Proalgesic mediators will cause pain by amplifying the incoming pain signals to the central nervous system (15).
  • Vasoactive mediators will cause blood vessels to constrict or dilate (16, 17).
  • Membrane permeable mediators can cross the blood-brain barrier and have effects on the central nervous system (like increasing sensitivity to stimuli) (18, 19).
  • Pyrogenic mediators will increase body temperature (20).

During a food sensitivity reaction, mediators are released by white blood cells and circulate all over the body, triggering lots of unpleasant symptoms.

This explains why someone who is suffering from a food sensitivity usually has multiple symptoms, not just one or two symptoms localized to one organ.

The best food sensitivity tests should be able to measure mediator release because that is what DIRECTLY causes your symptoms.

Who Should Get Tested?

If you feel like food may be contributing to your symptoms, but you can’t figure out which foods are to blame, food sensitivity testing might be helpful.

Unlike food allergies, which typically cause rapid symptoms, the symptoms of food sensitivities can be delayed up to 72 hours and are often dose-dependent. This can make it very difficult to pinpoint which foods are causing problems (5).

Symptoms of food sensitivities are wide-ranging and can vary quite a bit from person to person, depending on the way their body reacts and the types of mediators released.

The following is a list of symptoms that can be caused by food sensitivities (21, 22, 23):

  • Fatigue
  • Brain fog
  • Headaches
  • Mood swings
  • Sinus or ear congestion
  • Runny nose
  • Rashes or itchy skin
  • Achy joints
  • Nausea
  • Abdominal pain
  • Bloating and gas
  • Diarrhea
  • Constipation
  • Water retention
  • Unexplained weight gain or loss

You may also consider getting tested if you have health conditions linked to food sensitivities and chronic inflammation, such as:

  • Acne (24)
  • ADHD (25, 26, 27, 28)
  • Autism (29, 30)
  • Chronic fatigue syndrome (31)
  • Depression (32)
  • Eczema (33, 34)
  • Fibromyalgia (35)
  • Gastroesophageal reflux disease (GERD) (36, 37)
  • Inflammatory bowel diseases (38, 39, 40, 41)
  • Interstitial cystitis (42, 43)
  • Irritable bowel syndrome (IBS) (44, 45, 46)
  • Migraines (47, 48, 49, 50, 51)
  • Psoriasis (52)
  • Rheumatoid arthritis (53, 54, 55)

Of course, having any of these symptoms or conditions does not guarantee that you have food sensitivities, but typically, the more symptoms you experience, the better candidate you are for testing.

The best way to determine whether food sensitivity testing is right for you is to work with a dietitian or other licensed health care professional who specializes in adverse food reactions.

It is also worth noting that some people also choose to get tested for food allergies (via oral challenge, skin prick testing, and/or IgE blood testing) since food sensitivity testing is completely separate and cannot detect allergies.

Interestingly, while up to 35% of people report adverse reactions to certain foods, only 3.5% of them are actually due to true allergies. It is estimated that 50 to 90% of adverse food reactions are actually due to sensitivities or intolerances (56).

What Types of Tests Are Available?

There are many food sensitivity tests to choose from, but some are better than others.

Let’s review 11 of the most common food sensitivity tests and evaluate the science behind them.

1. Mediator Release Testing (MRT) + LEAP Diet

Mediator Release Testing (MRT) was invented by immunologist Mark Pasula as a way to identify food sensitivities.

How does it work?

MRT is a blood test that can be ordered through a healthcare professional or directly from Oxford Biomedical Technologies (in the US/North America) or ISO-LAB (in Europe).

To perform the test, the client gets their blood drawn and shipped overnight to a lab. (The overnight shipping is important to ensure that the blood cells are still alive for testing.)  

Once received, the blood sample is divided up and mixed individually with the 141 food antigens and 29 chemicals that are tested on the MRT panel.  

A machine then monitors to see how much the white blood cells shrink in size after exposure to these antigens.

The more the cells shrink, the more pro-inflammatory mediators they have released, and the stronger the food sensitivity reaction is (57, 58).

Say what?

Let’s break down the physiology.

At rest, when white blood cells haven’t reacted to anything, they are storage houses for various types of mediators.

That means when no reaction has occurred, your blood has a relatively stable solid-to-liquid ratio. (Solid cells filled with mediators, floating around in the liquid portion of your blood.)

However, when these white blood cells are exposed to an antigen, they respond by releasing some of their mediators into the surrounding environment, which causes them to shrink in size.

This then CHANGES the solid to liquid ratio of your blood.

The more mediators your white blood cells release, the smaller they get, and the more the solid-to-liquid ratio decreases.

This is a totally normal process that occurs constantly as our immune system evaluates its environment (this process is commonly referred to as the “oral tolerance” process).

A moderate amount of mediator release is a normal part of the oral tolerance process.

In a healthy functioning immune system, this minor inflammatory reaction is counterbalanced by the release of anti-inflammatory mediators to neutralize the reaction (59).

However, if the immune system detects something that it deems a threat, it will go hog-wild and release A LOT of pro-inflammatory mediators, causing a much larger than “normal” reaction.

This abnormal change in the solid-to-liquid ratio is then flagged on the MRT test results as either “moderately reactive” or “highly reactive,” depending on the size of the response.

How are these changes actually measured?

MRT uses two types of technologies (flow cytometry and impedance technology) to measure changes in the solid-to-liquid ratio of the blood.

In regular people terms, this means that the blood passes through a fancy machine that uses lasers and electrical currents to determine the volume of solid particles within the blood (60).

Since each person is unique, they serve as their own control for the test. Only changes in the solid-to-liquid ratio that are several standard deviations from “normal” for that individual are flagged as reactive.

One of the strengths of the MRT test is that you can actually see the magnitude of each response on the test results, as indicated by the length of each bar:

(Image used with permission from Oxford Biomedical.)

This is really helpful when trying to decide which foods to include at which stages of an elimination diet.

Another positive of the MRT test is that they use high-quality “lyophilized antigens” (which basically means freeze dried) that have not been denatured or otherwise changed by harsh extraction methods (61).

The goal is to use antigens that are as close as possible to what the immune system would encounter in the gut if those foods were eaten.

Finally, another unique benefit of MRT is that they not only test food antigens but also chemicals like caffeine and amines that naturally occur in foods.

This gives dietitians the ability to customize their patient’s diet to avoid foods that contain these triggering substances.

MRT can detect both type III and type IV food sensitivity reactions.

This is probably one of the most important concepts to wrap your head around in regards to food sensitivity testing.

MRT measures the amount of mediators released from your white blood cells.

Mediators are what cause food sensitivity symptoms, so they are the MOST IMPORTANT thing to measure.

We don’t really care which pathways triggered their release.

It could have involved antibodies, like IgG, or the white blood cells could have been triggered directly without the involvement of antibodies.

Again, it doesn’t really matter.

What we ultimately want to know is DID mediators get released in response to a certain food or chemical. THAT is the clinically relevant information.

The importance of working with a Certified LEAP Therapist (CLT)

MRT can be ordered directly from Oxford Biomedical Technologies, but it is HIGHLY recommended that you work with a Certified LEAP Therapist (CLT) for the best results.

CLTs are registered dietitians who have passed the CLT certification offered by the creators of the MRT test.

CLTs have been educated on the physiology of food sensitivities, trained on how to interpret MRT test results, and taught how to implement a customized elimination diet known as LEAP.

LEAP stands for “Lifestyle Eating and Performance,” and refers to the elimination diet that is used along with your MRT results.

The LEAP protocol usually lasts 6 to 8 weeks, becoming progressively less restrictive as new foods are introduced.

For the first 2 weeks, you eat roughly 25 of your lowest reactive foods (preferably ones you already eat on a somewhat regular basis so your immune system is familiar with them) in order to calm diet-related inflammation and allow for symptoms to subside.

Then, once you are actually feeling better, you can begin to add foods back in, one at a time, from least reactive to more highly reactive, watching for any reactions that may occur.

This is done under the supervision of a “Certified LEAP Therapist” (CLT) who has been trained to interpret MRT results and help patients complete the LEAP protocol.

It is important to note that the foods labeled as “reactive” on your MRT results should NOT be blanket-statement avoided forever. It is important to work with your dietitian to eventually add them back into your diet and test your tolerance.

It IS possible (although not guaranteed) to regain oral tolerance to some foods, and unnecessary restriction should always be avoided.

It is also incredibly important to understand that testing can give you a starting point for doing a customized elimination diet, but it is NOT the end-all-be-all.

Food sensitivity testing does NOT test for allergies, intolerances, or other types of possible adverse reactions that can occur, such as intestinal allergy (allergies that only manifest in the gut) or histamine intolerance.

Because of this, you should always let your body be the guide, and listen to its responses above all.

To find a CLT near you, go to HealthProfs.com, type in your zip code, filter the search results for “Nutritionists and Registered Dietitians” and then click “Certified LEAP Therapist” under “Treatment Techniques” on the left-hand side.

Many CLTs work remotely (via phone or video chat), so it is worth expanding your search if there are no CLTs in your immediate area.

Is there evidence to support this test?

While there is a large amount of research to support the involvement of food sensitivity reactions in chronic inflammatory conditions, there is very little research on food sensitivity tests themselves.

As of November 2018, no peer-reviewed research studies have been published on MRT or the LEAP elimination diet. However, preparations are underway for a future study on the effectiveness of LEAP for IBS-D.

While no studies have been published in peer-reviewed journals, a small amount of data has been published or presented elsewhere:

    • LEAP reduces IBS symptoms: A clinical presentation given at the 2004 annual meeting for the American College of Gastroenterology showed that the LEAP diet (guided by MRT results) decreased IBS symptoms by 53% in one month (62).
    • LEAP reduces circulating cytokines: A follow-up study on a single subject with IBS-D showed an increase in circulating cytokine levels during an IBS-flare and lower levels of cytokines when symptoms were in remission (62).
    • IBS patients have more circulating cytokines: To follow up the single-subject experiment, cytokines in the blood were compared for a group of normal healthy adults and those with IBS. IBS patients had significantly higher levels of many types of pro-inflammatory cytokines compared to controls (62).
    • MRT has 94% sensitivity and up to 91% specificity: A study published by the Polish Pediatric Association found that MRT detected food sensitivity reactions to at least one cow’s milk protein in 94% of milk-allergic children who displayed symptoms after an oral challenge and had a 16% false-positive rate in healthy adults with no symptoms (63). A second data set showed that 91% of the tested items were negative for healthy asymptomatic adults (64).
    • Greater than 90% split-sample reproducibility: Oxford Biomedical is a CLIA accredited lab which must pass quality control measures biannually. MRT advertises a greater than 90% split sample reproducibility, but only provides one example to back up these claims (65).

While high-quality research is still lacking, this doesn’t mean that the test isn’t “evidence-based” (66).

According to an article published in the Journal of The American Dietetic Association (now the Academy of Nutrition and Dietetics), “evidence-based practice uses the best available evidence, the results of peer-reviewed scientific studies, whenever possible, and, when the science is lacking, expert opinion and experience” (67).

In this case, the research to support this specific testing method is lacking, but the physiology behind it and the theory of why it works is solid.

Food sensitivity reactions that cause systemic inflammation are a REAL thing and have been well studied and published on for decades.

It is also well established that many chronic illnesses have an inflammatory root, in which food often plays a role.

MRT helps connect these dots by determining which foods are contributing to the inflammatory load.

These foods can then be temporarily removed during the LEAP protocol to reduce inflammation while oral tolerance is restored.

Although testimonials are not enough evidence alone to support a test or protocol, it is worth noting that thousands of practitioners use MRT and LEAP with great results (68).

The Verdict: MRT is generally considered to be the best food sensitivity test available since it can detect mediator release caused by BOTH type lll and type IV hypersensitivity pathways. However, peer-reviewed research is needed for both MRT and the LEAP protocol.

(Looking for more supporting research on this topic? Check out The Functional Nutrition Library.)

2. Antigen Leukocyte Antibody Test (ALCAT)

Similar to MRT, the aim of ALCAT is to measure the amount of mediators released by white blood cells in response to different food antigens.

It was actually developed in the 80’s by Dr. Pasula (the same guy who created MRT), but Dr. Pasula eventually separated from that company and created MRT using newer technology for more accurate results.

How does it work?

ALCAT works much in the same way as MRT. The client orders the test through a healthcare provider or directly from Cell Science Systems (North America only), gets their blood drawn locally, and mails the sample overnight to the lab.

Like MRT, the patient’s blood sample is exposed to a variety of antigens and monitored for changes in cell sizes.

However, ALCAT uses an older impedance technology, which is not quite as accurate as the more modern (but patented) three-dimensional ribbon impedance methods used by MRT (69).

Additionally, the way ALCAT presents its results is different than MRT.

Rather than being presented as a bar graph (which indicates the magnitude of the immune response), ALCAT results are grouped into 4 broad categories:

  • Acceptable Foods
  • Mild Intolerance
  • Moderate Intolerance
  • Severe Intolerance

However, as we know, there can be a wide range of reaction-sizes, even within the “low-reactive” or “acceptable” categories.

It is very helpful to know which foods provoke the least amount of inflammation when designing an oligoantigenic elimination diet.

Since ALCAT doesn’t quantify the degree of reactivity within each category, there’s no way to know exactly how much inflammation is caused by any given food.

Additionally, the dietary therapies recommended by ALCAT and MRT differ as well.

MRT promotes a customized oligoantigenic diet (LEAP) based on a person’s test results, whereas ALCAT promotes a rotation diet with all “acceptable” foods, followed by the eventual reintroduction of reactive foods to test for tolerance (70).

The LEAP diet is more restrictive in the initial phases, but also more highly customized, and thus more likely to produce rapid symptom relief.

However, there are still a few benefits of ALCAT.

One benefit of ALCAT is that it tests for a wider variety of antigens (357 on ALCAT vs 170 on MRT), including foods, herbs, food additives, medications, and even molds.

However, a larger testing panel also introduces more opportunity for error, false-negatives, and false-positives that may hinder someone’s attempt at an elimination diet.

However, ALCAT does not test for as many naturally occurring chemicals (like caffeine or amines) as MRT.

Like MRT, ALCAT also uses freeze-dried antigens to mimic what the immune system would see when the food is consumed.

ALCAT is able to detect both type III and type IV food sensitivity reactions, so it is still more clinically useful than IgG testing (71).

Is there evidence to support this test?

There is a combination of peer-reviewed and non-peer-reviewed data to support ALCAT:

Non-Peer-Reviewed:

  • ALCAT can distinguish between people with food sensitivities and healthy controls: Data presented at a 1988 immunology conference found that healthy young adults had significantly fewer positive results on the ALCAT test vs people with suspected food sensitivities (2% vs 20% positive results) (72).
  • ALCAT + avoidance diet can improve symptoms of migraine, eczema, and rhinitis. Data presented another conference in 1988 showed that 77% of migraine sufferers, 71% of eczema patients, and 100% of rhinitis patients experienced symptom relief after removing foods that were “reactive” on the ALCAT test. Only 50% of IBS patients improved, likely because roughly ⅓ of them actually had yeast overgrowth, not IBS (73).
  • ALCAT has 79% sensitivity and 87% specificity for foods: Data presented at a 1996 conference showed that 79% of foods marked as “reactive” on ALCAT provoked symptoms during an oral challenge, while 87% of foods not reactive on the test did not cause oral challenge symptoms (74).
  • ALCAT has 95% sensitivity and 92% specificity for food additives: Again, data presented at a conference found that 95% of food preservatives and colorings that tested positive on ALCAT also elicited symptoms in a double-blind placebo-controlled test and 92% of the non-reactive additives did not elicit any symptoms (75).

Peer-Reviewed:

  • An ALCAT-based elimination diet can improve IBS symptoms: In a 2017 double-blind randomized controlled trial, IBS patients experienced greater global improvement and significantly reduced symptom severity after a 4-week ALCAT-based elimination diet compared to a sham diet. No differences in quality of life measures were seen between groups, and there was a clear (but less significant) placebo effect from the sham diet. Mean symptom score improvement was better than that seen with low-FODMAP diets (76).
  • ALCAT can identify non-celiac gluten sensitivity just as well as a blinded food challenge: ALCAT and a blinded gluten challenge both correctly identified 64% of people with non-celiac gluten sensitivity (77).
  • ALCAT can identify foods that induce DNA release from white blood cells: 70% of foods that tested reactive on an ALCAT test have been shown to elicit a greater release of DNA from white blood cells (which then kicks off an immune response). This lends support to the theory behind ALCAT (and MRT) (78).
  • ALCAT has 72% sensitivity and 82% specificity: In a different set of data published in The Journal of Nutritional Medicine, 72% of the foods that tested positive on an ALCAT test elicited IBS symptoms, while 18% of foods that did not test reactive also produced symptoms (79).
  • An avoidance diet based on ALCAT results improves IBS symptoms: In the same study, 2/3rds of the IBS patients experienced significant symptom relief within 2 weeks of eliminating foods that were reactive on ALCAT (79).

The Verdict: ALCAT is considered the second-best option behind MRT. It also measures mediator release from white blood cells, but uses slightly different technology, presents the results in a different manner, and recommends a less specific diet-therapy than LEAP. However, it does have more published research than MRT at this time.

3. Immunoglobulin G (IgG) Testing

IgG testing is probably the most popular and well-known type of test for food sensitivities. Sadly, its clinical utility doesn’t measure up to its popularity.

How does it work?

Like the previous tests, clients have a blood sample taken and then mail their blood to a lab.

The blood sample is then mixed with a variety of food antigens, and the levels of IgG antibodies are measured via ELISA or RAST.

If elevated levels of IgG antibodies for a particular food are detected, then the results will show that you are “sensitive” to it.

However, a large body of research has found that the presence of IgG antibodies alone does NOT indicate a food sensitivity (80).

In fact, some studies have suggested IgG may be a marker of food tolerance rather than a food sensitivity (8081, 82).

The truth is, IgG production is a normal part of the oral tolerance process.

Most companies (like Pinnertest, EverlyWell, Cyrex, and Genova Diagnostics) test total IgG or IgG4 levels. However, there are a few labs that measure other components as well:

  • IgG, IgG4, IgE, + Complement (Dunwoody Labs): This lab can test for both allergies (IgE) and sensitivities. By testing both IgG4 and total IgG, it can better discriminate between protective and pathogenic responses (83). A moderate amount of IgG4 can be protective, whereas large amounts can drive inflammation. Additionally, if complement is produced, a reaction may be more severe (84).
  • IgG + Complement (KMBO): Similar to Dunwoody, KMBO measures IgG and complement, but it does not measure IgG4 or IgE.
  • IgG + IgE (Meridian Valley Lab): This test checks for both IgG AND IgE antibodies, but the results don’t specify which one was produced in response to which foods. Instead, both types of antibodies are all lumped together, so there’s no way of knowing whether you might have an allergy, a sensitivity, both, or neither.
  • IgG + IgA (Alletess): Looking at both IgG and IgA antibodies is slightly more comprehensive than IgG alone but still misses type IV reactions.

Is there evidence to support this test?

Testing of IgG levels is accurate, but the problem is that it is just not clinically useful (85, 86).

  • In some cases, IgG may be protective against adverse food reactions.
  • The presence of IgG does not always = an inflammatory response.
  • There is no clear correlation between IgG levels and symptoms.

Sure, some of the foods that test positive on an IgG test MAY, in fact, be triggering food sensitivity reactions.

Therefore, eliminating all of them may help people feel better if they were able to get rid of some of their biggest dietary triggers.

This may explain why some studies HAVE seen improvements in IBS and migraine symptoms after eliminating foods that tested positive on IgG tests (87, 88, 89).

However, a person may NOT feel better after eliminating “reactive” foods on their IgG test if their worst food sensitivity reactions are NOT caused by IgG antibodies.

Remember, there are multiple pathways that can cause food sensitivity reactions, and IgG is just one. IgG testing cannot detect type IV hypersensitivity reactions.

Additionally, there is a big chance of over-restricting the diet based on IgG test results alone, so it is important to eventually reintroduce reactive foods back into the diet and monitor the body’s response.

IgG testing has been well researched, and many associations have released statements that it should NOT be used for the detection of food sensitivities.

These include the European Academy of Allergy and Clinical Immunology, the American Academy of Allergy, Asthma, and Immunology, and the Canadian Society of Allergy and Clinical Immunology (90, 91, 92).

The Verdict: Overall, IgG tests are appealing because they are quick and relatively cheap, but they are not good indicators for food sensitivities. IgG production is a normal part of the oral tolerance process, and may actually indicate exposure or tolerance to a food.  IgG testing does not measure mediator release (which is what actually causes symptoms) and cannot detect type IV hypersensitivity reactions.

4. LRA by ELISA/ACT (Advanced Cell Test)

LRA was developed by Dr. Russell Jaffe in 1984 as a way to detect food sensitivities. It stands for “Lymphocyte Response Assay.”

How does it work?

Like the previously mentioned tests, the client orders this test through a health care provider or directly from ELISA/ACT Biotechnologies, takes a blood sample, and mails it overnight to the lab.

Up to 504 antigens can be tested, including foods, additives, molds, dander, medications, and herbs.

Unfortunately, the details of exactly how this test is performed are very vague on the ELISA/ACT website.

Based on the information provided in this peer-reviewed study, we determined the following:

Once the sample is received, the blood is then centrifuged to isolate the lymphocytes and plasma.

This mixture is placed inside wells that contain an antigen bound to their surface and incubated for 3 hours.

The samples are then evaluated by hand using a light microscope.

Five different fields of view are examined per well, and the results are averaged. (This leaves a lot more room for error than other tests that use automated calibrated machines.)

A reaction is flagged and considered “moderate” if 25 to 50% of the lymphocytes in the well “show activation” or considered “strong” if more than 50% of the cells “show activation.”

“Show activation” is defined as a symmetrical increase in the volume of the glycocalyx (the outer layer surrounding the cell).

Asymmetrical increases in volume are considered to be “false positives” and are ignored.

The assumption is that this increase in volume is caused by the activation of the major histocompatibility complex (MHC) of the white blood cell, which triggers an immune response.

However, there is no research provided to support this assumption.

These results are then compiled in a document and sent to the practitioner or patient. Clients are advised to avoid strongly reactive items for 6 months and moderately reactive items for 3 months before trying again.

Is there evidence to support this test?

One of the most worrisome parts about this test is the lack of transparency about their testing methodology and the major scientific inaccuracies on their website.

For example, this table comparing and contrasting LRA to MRT, ALCAT, and IgG testing incorrectly classifies the different reaction types and misunderstands entirely what MRT & ALCAT measure.

Another weakness of this test is that LRA proclaims to analyze lymphocytes, but that leaves out an entire other class of white blood cells, known as granulocytes, that can also participate in food sensitivity reactions.

The makers of the test claim that it has less than a 0.1% false-positive rate and less than 1% false negative rate (93).

However, there is no public data available to support these claims and there have been no published studies regarding the reliability or validity of LRA.

One peer-reviewed study published in the Journal of Musculoskeletal Pain showed an improvement in fibromyalgia symptoms after removing foods that tested positive on LRA, but the study was not blinded or randomized and is horribly confounded by the use of supplements and clinical support groups in the treatment protocol (94).

The Verdict: LRA is not a good choice for food sensitivity testing. Its testing methodology is not clearly explained, and it only examines one type of white blood cell (lymphocytes), leaving out an entire class of food sensitivity reactions that involve granulocytes. There is no high-quality research of any kind to support the use of this test.

5. Cytotoxic Testing

Cytotoxic testing (also known as Bryan’s test) has been around since 1947 as a way to identify food sensitivities (95).

How does it work?

A blood sample is taken and centrifuged (spun around in a machine) to separate the white blood cells.

The cells are mixed with plasma and water and placed on glass slides that have various dried food antigens on them.

The slides are then examined under a microscope after 2 hours to look for changes in the size, shape, or number of the cells.

The idea is that a large number of shrunken, dead, or damaged cells indicates a food sensitivity to that antigen.

Is there evidence to support this test?

Unfortunately, since this test is done by hand, there is a lot of room for error and it is not considered to be very accurate or reliable.

Additionally, since the practitioner is only looking at the cells on a two-dimensional slide, there is no way to tell for sure whether the cells just changed shape or if they actually shrunk in size.

There are also many other factors that could affect the size/shape/activity of white blood cells, including the pH, temperature, incubation time, and possible contaminants on the slides that are not well controlled for with this method (96).

A study done in the 70’s found that 73% of the results were reproducible in 5 out of 6 tests done on the same person, but that the results didn’t correlate well with the person’s self-reported symptoms (97).

However, this is not surprising since food sensitivities are often delayed and dose-dependent and can’t typically be identified just by asking someone which foods they think they react to.

Cytotoxic testing has been deemed “ineffective and without scientific basis” for the detection of allergies (but no mention of sensitivities) by the FDA and the American Academy of Allergy (98, 99).

The Verdict: Given the large potential for error with cytotoxic testing, it is rarely used anymore and is not recommended for the detection of food sensitivities.

6. Live Blood Analysis (LBA) by Darkfield Microscopy

Live blood analysis (also known as live cell analysis, nutritional blood analysis, or Hemaview) is a test sometimes used by alternative medicine practitioners and chiropractors to diagnose food allergies or sensitivities (100).

How does it work?

The test is performed at a practitioners office, where a drop of blood from a finger prick is placed on a microscope slide under a glass coverslip.

The blood is then viewed using a “dark-field microscope,” which shines light from underneath the slide, rather than above.

This creates a dark background and bright cells in the foreground, which can be displayed on a television monitor for easier viewing.

According to Live Blood Online, a company that offers training in this method, the practitioner then examines the blood for “abnormalities” in the size, shape, ratio, or structure of red and white blood cells, platelets, and more.

However, it is unclear how any of these abnormalities would relate specifically to food sensitivities, or how you would obtain any information about what you are sensitive to.

The Weston A. Price Foundation published a small (non-peer reviewed) study in its own newsletter, suggesting that live blood analysis may be a valuable tool for evaluating blood clotting patterns and that people with higher inflammation levels may have faster rates of clotting (101).

While it is true that inflammation is linked to blood clotting, it is unclear how live blood analysis would help someone understand whether food was playing a role in their inflammation levels or which foods might be problematic for them (102).

Is there evidence to support this test?

While this technique IS considered a valid scientific tool for examining blood cells and detecting certain types of bacteria in the blood, to date, there is no research to suggest it should be used for the evaluation of food sensitivities (103, 104).

As of 2001, no live blood cell analysis provider had been able to meet the requirements of CLIA (Clinical Laboratory Improvements Amendments of 1988) and live blood analysis remained classified as an unestablished laboratory test (105, 106).

The Verdict: Live blood analysis can be a useful tool in some situations, but NOT for food sensitivity testing. There is no research to support its use for this purpose, and it is unclear how it would be helpful.

7. Electrodermal Test (Vega)

The Vega test (also known as electrodermal testing) was invented in the 1970’s as a way to diagnose food allergies or sensitivities (107).

How does it work?

Electrodermal testing uses a type of “electroacupuncture,” in which an electric current is passed through the body using two pieces of equipment, usually a hand-held probe and a second smaller probe placed on acupuncture points by the practitioner.

A “Vega machine” is then connected to the same circuit and a test substance (like a heavy metal) is placed inside the machine.

If the machine shows a drop in the reading when exposed to this “toxic” substance, the machine is considered properly calibrated.

The practitioner then repeats this process, placing a variety of foods in the machine one by one, watching for changes in the electrical readings (skin impedance) after exposure.

The idea is that when the body is exposed to a food or other substance it does not tolerate, it triggers an autonomic (subconscious) nervous system response that changes the way electricity is conducted through the skin (107).

Since the Vega machine is monitoring how quickly electricity passes between the two probes, it can pick up on these small changes.

Based on the results, the practitioner will provide a list of reactive foods or substances to avoid.

Is there evidence to support this test?

While it is possible to measure changes in skin impedance with the Vega machine, it is unclear how those changes might relate to food sensitivities, specifically.

Published data has only focused on IgE allergies and is wildly inconsistent, ranging from no correlation with skin prick results to a 90% correlation (107, 108, 109, 110).

However, since these studies involved allergies, not sensitivities, it is unclear whether electrodermal testing might be helpful for other types of hypersensitivity reactions.

Issues that make electrodermal testing less reliable include possible user error (applying the electrodes with the right pressure) and the potential for over-testing in one area (107).

It also cannot be used on anyone with a pacemaker and can be affected by things like battery-powered watches, fluorescent lighting, or a high electromagnetic field in the area (107).

The Verdict: While electrodermal testing has its proponents, it is unclear how changes in skin impedance would indicate food sensitivities, and there have been no studies done to evaluate its effectiveness for this purpose.

8. Hair Testing

Recently, a few companies have been advertising hair testing as a method for detecting food allergies, sensitivities, and intolerances.

How does it work?

The client collects a sample of their hair and mails it to the company.

The sample is then “analyzed” and the customer receives a report showing their food and environmental sensitivities.

Is there evidence to support this test?

There is no validated method of testing sensitivities or intolerances through hair.

Several hair testing labs report that they use “bioresonance” machines to test hair for food sensitivities (111, 112, 113).

These machines are designed to detect an individual’s “morphogenetic field encryption pattern” – a pattern of energy that can supposedly be measured in any cell of an object (114).

The idea is that certain foods or substances disrupt this energy pattern, which can trigger the immune system & contribute to chronic illness.

Some practitioners then recommend “bioresonance therapy” to “rebalance” the energy fields and correct a variety of illnesses.

However, studies on this topic have been low-quality and with mixed results (115, 116, 117, 118, 119).

While this is an interesting theory, at this time, there is no science to support the existence of morphogenetic fields, and no data to link it to food sensitivities, allergies, or intolerances (120, 121).

The Verdict: While hair testing may be useful for other purposes, such as the detection of heavy metals, there is no research to support its use for food sensitivity testing.

9. Coca Pulse Test

Pulse testing for food allergies and sensitivities was first described by Dr. Arthur F. Coca in 1956 (122).

How was it developed?

Dr. Coca’s wife began experiencing unexplained chest pain one day, and she noticed that her attacks were the worst within minutes after eating certain foods. He tested her pulse after she ate these foods and found that it was faster than usual.

So, they began tracking everything she ate and testing her pulse before and after eating each food. She removed the foods that seemed to elevate her pulse, and she found that her chest pain was gone.

He began practicing this technique on many of his patients and claimed to have “almost miraculous” results.

Is there evidence to support this test?

Unfortunately, there’s not much research to back up these claims.

It is true that some types of food sensitivity reactions can trigger the release of mediators that affect heart rate, so the mechanism is plausible.

But, since food sensitivities are dose-dependent and often delayed, pulse-testing would not be a very reliable method unless the food triggered a very clear and rapid response.

It is also important to note that pulse rate can be affected by many other factors, including your own emotions or thoughts about the food.

A small study from 1961 got mixed results with pulse testing and questioned its usefulness in clinical practice (123).

The Verdict: The mechanism behind the Coca pulse test is plausible, however, pulse rate can be affected by so many other factors and food sensitivity reactions are not always immediate, so it is probably not a very reliable way to test for sensitivities.

10. Applied Kinesiology (Muscle Testing)

The use of applied kinesiology, or muscle testing, to assess food sensitivities is gaining popularity and is practiced by nearly 40% of chiropractors (124).

How does it work?

This test is performed in an office by practitioners trained in this method.

There are various ways to perform the test using different muscles of the body, but the most common uses an extended arm (testing the deltoid muscle in the shoulder).

To do the test, the patient is asked to hold a vial of a substance in one hand (or place a substance under the tongue) and hold the other arm out to the side, parallel to the floor.

They are asked to keep their arm in place, without pushing upwards, while the practitioner pushes down on the arm from above.

If the arm holds strong and does not move, the body is considered to be tolerant of the food or substance the person is holding at the time.

If, however, the limb weakens and moves when force is applied, it is believed that the body does not tolerate that food.

This test can be repeated using a variety of vials containing different substances.

The belief behind this testing is that the body has energy pathways (called “meridians” in Traditional Chinese Medicine) that can be affected by food or other environmental triggers.

When these energy pathways are disrupted, the body is “weakened,” as detected by muscle testing.

The practitioner will then recommend avoiding the foods or substances that weaken the body in order to improve health.

Proponents of this testing method highlight that it is non-invasive and easy to perform, with immediate results.

Is there evidence to support this test?

There is currently no peer-reviewed evidence to support the use of muscle testing for the detection of food sensitivities.

Since it is administered by a person, there is large room for error, and interpretation can vary based on the training and experience of the practitioner.

Studies have attempted to validate its use for detecting true IgE allergies or reactions to known poisons, but have not had positive results:

  • Muscle testing cannot accurately detect allergies: One study found that muscle testing was unable to detect true IgE allergies to wasp venom and only had a 3% overall test-retest reliability, between and within practitioners (125).
  • Muscle testing results did not differ significantly from chance: A second study tested the same items twice, in a blinded manner, and only got the same results 33% of the time (126).
  • Muscle testing correctly detected vials of poison only 53% of the time: A study comparing saline solution to a toxic hydroxylamine chloride solution found that muscle testing was only able to detect the toxic vials 53% of the time (127).

While scientific evidence is lacking for muscle testing, there are many anecdotal reports of its usefulness and it is still widely used to this day.

Many who use it consider it to be just one tool in the toolbox, but not diagnostic of anything. Results should always be verified with labs when possible.

The Verdict: There is no research to support the usefulness of applied kinesiology for detecting food sensitivities. Most published research has found that it is not much better than chance at identifying problematic foods or substances.

11. Elimination Diets + Food Challenges

The gold standard for diagnosing adverse food reactions is called a “double-blind, placebo-controlled food challenge” (DBPCFC) (128).

While it is the most well-controlled and accurate method, it is also very time-consuming to do for multiple foods.

Because of this, DBPCFCs are most commonly used to test whether people are truly allergic to foods that have come back positive on a skin prick test, but that the person has never eaten.

This means that DBPCFCs are more commonly used in the context of IgE-mediated allergies, rather than delayed hypersensitivities, but they still can be used for this purpose.

How does it work?

A double-blind placebo-controlled food challenge is just what it sounds like.

It is double-blinded, meaning that neither the patient nor the practitioner knows which foods are being consumed when. This is so that their perceptions do not influence the results.

It is also placebo-controlled, meaning that the patient separately introduces the suspected problem food and a placebo substance (without knowing which one is which).

Before introducing either of these substances, the patient is put on a strict diet for a few days that only contains a few foods that are (presumed to be) well-tolerated.

This is done in order to wash out any reactions that might have been lingering from previous exposure, as well as to control the diet so the only thing that changes is the exposure to the test substances.

Then, under the supervision of a doctor, one set of capsules containing either a food antigen or a placebo is added to the diet in increasing dosages and the patient and physician document any reactions that occur. This is then repeated with the other set of capsules.

Symptom records are evaluated to determine whether an adverse reaction occurred or not. Only then is it revealed which capsules contained the food antigen, and which ones contained the placebo.

This method is helpful because you are only challenging one food at a time in a very controlled manner, so you can be relatively sure that any differences in symptoms are due to the food.

However, it isn’t very practical for most people, especially when you aren’t sure which food or foods might be causing your symptoms.

When conducted in the context of allergies, which typically have rapid-onset symptoms, a DBPCFC can be performed in a few hours at a doctor’s office (with an epi-pen on hand, just in case).

However, when conducted for delayed hypersensitivity reactions, it is more likely to be done at home over a longer time period, typically around 1 week.

Because DBPCFCs are relatively difficult to perform, they are not typically very helpful for detecting food sensitivities, especially if someone has no idea which food or foods might be the culprit.

For food sensitivities, elimination diets are more commonly used.

To conduct an elimination diet, a person “eliminates” a large variety of potentially problematic foods and only consumes a restricted diet until symptoms subside (usually a few weeks to 1 month)

Once the person feels significantly better, eliminated foods are systematically reintroduced to test for tolerance.

Some commonly used elimination or semi-elimination diets include Whole30, Autoimmune Paleo (AIP), and even low-FODMAP.

The most commonly eliminated foods include dairy, gluten, grains, legumes, nightshades, lectins, and/or highly-fermentable carbohydrates.

However, there is no guarantee that any of these foods are at the root of your symptoms.

It is quite possible to have hypersensitivity reactions to foods that are commonly considered “healthy,” like salmon, kale, quinoa, or turmeric.

Without guidance on which foods are actually triggering immune-mediated hypersensitivity reactions, blanket elimination diets can only get you so far.

You might get lucky and determine a few of your biggest symptom-triggers, but then again, you might not.

The Verdict: Double-blind placebo-controlled food challenges are considered the “gold standard” in identifying adverse food reactions but are very difficult and time consuming to do. There are a wide variety of elimination diets that can be used to identify problematic foods, but they are less personalized than elimination diets created based on food sensitivity testing results.

How Much Does Food Sensitivity Testing Cost?

Most food sensitivity tests cost several hundred dollars to perform, plus the cost of working with a dietitian or other practitioner that specializes in adverse food reactions.

However, it is important to remember that cheaper is not always better when it comes to lab work.

The majority of the low-cost options only measure IgG levels and cannot detect the other types of food sensitivity reactions (cell-mediated, type IV).

It is worth spending more money for a more clinically useful result.

Additionally, your appointments with a dietitian or other licensed healthcare practitioner are often covered or reimbursed by insurance, which can help lower the cost.

Which Test Is Best?

MRT and ALCAT are the only tests that measure the release of mediators, which are ultimately responsible for food sensitivity symptoms.

MRT, however, uses updated technology and the LEAP protocol to more accurately pinpoint which foods are causing problems, so it is generally considered to be the best.

This doesn’t mean that other tests can’t provide some potentially useful information, but MRT (paired with LEAP) will give you the most actionable results and best therapeutic diet.

Although no peer-reviewed studies have been published yet to confirm the validity of MRT, its methods are backed by science, and many people have experienced significant symptom relief after following the LEAP diet protocol.

Where Does Testing Fit in My Wellness Plan?

It is important to note that ALL medical tests are simply sources of information, but how you USE that information is what really matters.

Food sensitivity testing results should never be interpreted as a list of foods to avoid forever.

Rather, they should be used to craft a customized diet that will quickly reduce inflammation, followed by a period of diet expansion and symptom monitoring.

In the context of functional nutrition, testing for and addressing food sensitivities would fit into the “Remove” section of the 5-R protocol (Remove, Replace, Repopulate, Repair, Rebalance).

The idea is to identify and remove any foods that are contributing to systemic inflammation or causing other types of adverse reactions. Testing can often help streamline this process.

Again, it is important to recognize that food sensitivities are often the tip of the iceberg. They rarely occur in a vacuum.

Working with a functional-minded practitioner can help you address the root causes of your symptoms and help you achieve optimal health and wellness.

{Are you a healthcare practitioner who often works with food sensitivities? Join The Functional Nutrition Library to stay up to date with current research.}

Disclosures: Both Erica and Amy are Certified LEAP Therapists and choose to utilize MRT and LEAP in their private practices. However, they have no financial relationship with Oxford Biomedical and are in no way compensated for recommending MRT to patients or peers. Similarly, Amy and Erica do not have any financial ties to any of the other companies mentioned above.