Nagalase is advertised as an accurate early cancer detection method. Labs that offer this test state that this enzyme rises during the very early stages of cancer because cancer cells use it to suppress the immune system and augment cancer cell growth.
Does this test show as much promise as advertised? Read on to learn more about nagalase and the controversial research surrounding it and decide for yourself.
What is Nagalase?
Nagalase (α-N-acetylgalactosaminidase) is an enzyme that breaks down certain glycoproteins (sugars attached to protein) and glycolipids (sugars attached to lipids/fats). It has a very important role and is essential for the body to function normally .
We know this because people who lack this enzyme develop a disease called Schindler or Kanzaki disease .
How Nagalase Became (In)Famous
Nagalase can suppress the immune system by suppressing the activity of some very important immune cells called macrophages. Macrophages are white blood cells also called the “Pac-Men” because they devour invading microbes and altered cancer cells.
Specifically, nagalase breaks down the Gc protein (known as vitamin D3 binding protein or VDBP), which inhibits the production of the Gc Macrophage Activating Factor (GcMAF), .
A research group has found that invading viruses and cancer cells use nagalase to infect the host and spread [3, 4, 5, 6].
The logic is as follows: cancer cells and viruses (such as HIV and influenza) release nagalase. Nagalase blocks the production of GcMAF, thereby preventing the activation of macrophages (pac-men) and basically hindering your immune system from doing its job. With a deficient immune system, infections and cancer can develop unchecked.
The same research group has developed a treatment based on the GcMAF molecule. This treatment will activate your macrophages and boost your immune system, fighting off cancer and HIV. This treatment has also been implicated in autism, autoimmune diseases, and linked to a number of conspiracy theories [5, 7].
Low Nagalase: Schindler/Kanzaki Disease
Here is a fact: if your nagalase is not working (mainly due to genetic mutations) glycolipids and glycopeptides, which are normally broken down by this enzyme, accumulate in your tissues. This results in Schindler disease, a metabolic disorder that causes issues with the nervous system. It can manifest in 3 different ways :
- Type I: a severe infantile neurodegenerative disorder; children don’t survive past early childhood
- Type II: adult-onset disease that leads to mild cognitive impairment and skin lesions (also known as Kanzaki disease)
- Type III: an intermediate form; people with this type display different symptoms including seizures, autism, and/or heart muscle disease
Unfortunately, there is no treatment for this disease [8, 1].
High Nagalase Levels
Studies suggest that nagalase levels can increase in various diseases.
1) Viral Infections
Nagalase levels can increase during viral infections; this can suppress the immune system response. Influenza A and HIV patients may have increased nagalase activity in their blood [3, 4].
Since cancer cells release this enzyme, people with prostate, cervical, breast, and other cancers may have high levels of nagalase in their blood [5, 6, 9, 10, 11]. The more advanced the cancer, the higher the nagalase levels will be.
A study suggests that nagalase activity may be increased in children with autism .
Another study reported that compared to healthy people, autoimmune patients with lupus have higher nagalase activity .
5) Excess Alcohol Consumption
Finally, in an observational study of 100 people, alcohol-dependent individuals had significantly elevated nagalase levels compared to healthy individuals. After detoxification therapy, their levels decreased back to normal .
Nagalase Testing – Too Good To Be True?
Nagalase testing and GcMAF treatment sound great, especially in the context of cancer. But are they too good to be true? There are several red flags associated with the research.
GcMAF as a Cure-All
Here is the logic that the main research team used.
Nagalase suppresses the immune system, mainly by suppressing the production of GcMAF, the protein which activates our “Pac-Men” white blood cells. Hence, if we just give people GcMAF, their “Pac-Men” cells will become active and destroy all infections and cancer cells.
The team used the results of their studies to support the development of the miracle drug GcMAF. They have published research showing that treatment with GcMAF is effective for:
- Various cancers [5, 11, 6] – most of the patients reported as cured
- HIV  – patients with HIV reported to be cured
- Multiple Sclerosis  – GcMAF improves motor function
- Chronic fatigue 
- Autism  – GcMAF potentially helps with the suppressed immune system
Research Can’t Be Reproduced
Most of nagalase and GcMAF research has been done by a single person – Dr. Nobuto Yamamoto and a couple of associates in the 90s.
If Dr. Yamamoto and his colleagues had really uncovered such a golden ticket, other researchers would have followed, if not for funding, then for fame.
This hasn’t happened, but not because of a lack of trying. It turns out, other scientists have had trouble reproducing the results .
If something works, it should work no matter who performs the research.
Unfortunately, when scientists fail to show results, excitement dissolves and most journal publishers have no interest in the dull negative data. Therefore, it’s reasonable to assume that many have tried working with nagalase over the years and none succeeded.
Retracted Papers and Questionable Methods
There are serious issues with Nagalase and GcMAF research. In fact, several of the articles published by Dr. Yamamoto have since been retracted, including the articles about HIV, breast, and colon cancer [7, 17, 18]. Retractions were due to scientific misconduct.
Here are a couple of issues with these and their other not yet retracted papers:
- They involved an extremely small number of patients, often in single digits.
- Patients in the GcMAF studies also received standard cancer treatment, such as surgery, chemo, or radiation therapy. This makes it hard if not impossible to tell if the patients were cured by the new drug or the standard treatment.
- Studies didn’t check the presence or progression of tumors by any other markers except for nagalase. There is no proof that GcMAF actually had any effect on cancer – there is only proof that it decreased nagalase levels .
- There is no proof that GcMAF works on a molecular level – no studies involving immune cells or cytokines. Instead, authors make unfounded claims and falsely cite other studies .
- Research bodies, co-authors, and sponsors cited in these studies are nonexistent or were included without approval .
- These studies have no controls. This is a red flag for any kind of research.
No Success Stories
Nagalase studies date back to the ’90s and GcMAF studies to the ’00s with no recent quality research. It stands to reason that if people treated a decade ago have experienced a miraculous recovery, they would make this known and share it with others desperately in need of a cure.
But when you search for nagalase and GcMAF on the web, you will find doctors and companies recommending them. What you won’t find are actual people who’ve been treated with their success stories.
European organizations such as the UK Cancer Research and the Anticancer Fund warn against people and companies selling GcMAF .
Nagalase Blood Tests Marketed Today
Labs and doctors that advocate for this test say that nagalase levels are directly proportional to tumor burden. They suggest that this test can discover tumors before they are detectable by other means .
However, although it’s said that this test is accurate for early cancer detection (this is the test’s main selling point), this makes no sense if this enzyme also increases in viral infections, autoimmune diseases, or simply when alcohol is consumed. If it doesn’t significantly increase solely due to cancer, nagalase can’t be a cancer screening method.
Some labs that have previously offered this test have since discontinued it, citing it as unreliable and not universally reflecting tumor burden.
If you do want to test your levels, by all means, you can do so. But don’t panic if the results come back elevated. Your immune system is often fighting various infections.
Studies report ranges from 0.23 to 0.39 nmol/min/mg in healthy individuals and up to 8 nmol/min/mg in cancer patients .
Note that other study groups had issues reproducing these ranges .
According to some research labs, normal levels are below 0.95 nmol/min/mg .
Nagalase Prospects are Few
While nagalase and GcMAF may have a role in the immune system, the issue is that the studies involving them were seriously flawed.
At the moment, a company in Japan offers GcMAF treatment and another company in Israel has purchased the rights for developing GcMAF as a drug.
It’s not impossible that we will hear more about nagalase and GcMAF in the future, but the chances are slim.