Is Methylglyoxal in Manuka Honey Safe?

Manuka honey is the most popular honey for scientific studies or research purpose. It is best known for its medicinal properties and hence also known as Medicinal Honey. It is prepared by the nectar extracted from the pinkish white flower of the wild Manuka tree.

Manuka tree is scientifically known as Leptospermum species. It is produced by the common European honey bee Apis mellifera. Manuka honey is the native product of Australia, New Zealand as Manuka trees are native to that place. Manuka honey is a very special type of honey as it can be used to treat various diseases.

The unique Manuka factor of Manuka honey is what makes it special. This unique Manuka factor is also used to keep a check on the quality of the Manuka honey when marketing it. Unique Manuka Factor or UMF is the registered trademark of Manuka honey worldwide which represent the non-peroxide antibacterial activity of Manuka honey.

UMF is defined as the concentration of the phenol with same antibacterial activity as the same concentration of honey.

Manuka honey is a potent anti-inflammatory, antioxidant and antimicrobial agent. There are various components present in Manuka honey which is responsible for its activity. Some components are known while some are still unknown (unique Manuka factor).

Honey contains more than 200 of the substances in it which include: sugars, water, vitamins, minerals, amino acids, enzymes, various phenolics, flavonoids, hydrogen peroxide and some amount of methylglyoxal.

All these components provide Manuka honey antibacterial, antiviral, antifungal, antioxidant and anti-inflammatory activities.

What is methylglyoxal?

Methylglyoxal is an organic compound with molecular formula C3H4O2. It is also known as 2-oxopropanal. It is a derivative of pyruvic acid (an end product of glycolytic pathway), hence also known as pyruvic aldehyde. It is the part of various metabolic processes in cells and intracellularly synthesized by many enzymes.

It is the component of many food products like various types of honey most importantly in Manuka honey. It is very commonly found in the processed, cooked or stored food. It is used in industries as a chemical and supplied as 30% aqueous solution.

Properties of methylglyoxal

  • It appears yellowish- green in colour.
  • It can exist as both viscous liquid and vapours.
  • It is slightly acidic in nature.
  • It has a pungent odour.
  • It is soluble in both water and alcohol.
  • It is highly reactive in nature.
  • Density of methylglyoxal is slightly more than water.
  • On heating it emits smoke and irritating fumes.
  • It is easy to polymerise.
  • It is hygroscopic (ability to retain water).
  • It is produced in various enzymatic and non-enzymatic reactions in the cell.

Health Benefits of methylglyoxal

Since Manuka honey is preferred as medicinal honey more than any other honey. And it contains methylglyoxal as the only distinguished component in it.

So it is quite predictable that medicinal property of Manuka honey is due to its high methylglyoxal content. Here are some benefits which Manuka honey has due to its high methylglyoxal content.

It is used as a flavoring agent

Methylglyoxal is used as flavouring agent in various foods and beverages. This has been approved by the World Health organization in 2001 that use of methylglyoxal as flavouring agent is safe to a certain level of intake.

FEMA (Flavour and Extract Manufacturers Association) further confirm and publish the report on GRAS (generally regarded as safe) substances which also state thatpyruvic aldehyde is safe to use as flavouring agent.

What does this mean?
Methylglyoxal is used in the food industry as a safe flavouring agent.

It is a potent antibacterial agent

Methylglyoxal is an antibacterial agent. Most of the antibacterial activity of Manuka honey is due to its methylglyoxal content this has been proved in various studies by diluting the Manuka honey.Also the bacterial biofilm in various diseases can easily be treated using methylglyoxal augmented Manuka honey

Cokcetin NN et al discuss in their paper that the non-peroxide antibacterial activity of Manuka honey is due to its high methylglyoxal content.

Bulman SE et al study the effect of methylgloxal fibres on bacterial infection in wound. They use these fibres as wound dressings to treat infected chronic wounds. And found that methylglyoxal has strong antibacterial activity against the wound infection.

Hayashi K et al found in their study that methylglyoxal inhibits the growth of multi drug resistant bacteria Pseudomonas aeruginosa. They found that methylglyoxal at concentration of 128-512 micro gram/litre can effectively inhibit the growth of this bacteria.

Rabie E et al study the mode of action of methylglyoxal on bacteria. They in their study describe that the methylglyoxal in Manuka honey is responsible for reducing motility of the bacteria by de-flagellation (removing flagella) of the bacteria.

Methylglyoxal can inhibit the growth of both gram positive and gram negative bacteria. They further explained that at 2mM concentration of methylglyoxal the bacteria completely losses the flagella and fimbriae on it. This also prevents the adhering of the bacteria and hence it can’t grow.

What does this mean?
Methylglyoxal is responsible for most of the non-peroxide antibacterial activity of the Manuka honey.

It helps as an antiviral agent

Methylglyoxal also has antiviral effects. It is capable of inhibiting the activity of many viruses. Manuka honey antiviral effect is due to the high methylglyoxal content in it.

Charyasriwong S et al study the effect of methylglyoxal against the influenza B virus. They found that 23-140microM of methylgloxal can have 50% inhibitory activity on the influenza B virus.

In another study Charyasriwong S et al showed that methylgloxal with some neuraminidase inhibitors methylglyoxal completely treat the influenza virus infection.

What does this mean?
Methylglyoxal is a potent antiviral agent against wide range of viruses.

It has anticancer property

Methylglyoxal is well known for its anticancer activity as it kills cancerous cells and inhibit their growth. Methylglyoxal is considered as natural growth regulator. Methylglyoxal attacks at the altered site of the cancerous cells like mitochondrial complex and some enzymes.

Talukdar D et al conducted a study on 86 patients suffering from cancer to see the effect of methylglyoxal on cancer. The result of the study shows that methylglyoxal is very effective in treating the cancer for most of the patients.

Yi Guo et al study the effects of methylglyoxal on breast cancer. The study shows that methylglyoxal inhibit the cancer cell proliferation, and also induce apoptosis of the cancerous cells.

Aparajita Pal et al use methylglyoxal with chitosan nanoparticles to treat cancer in mice and they obtain positive results.

What does this mean?
Methylglyoxal can be very helpful in treating various types of cancer without causing much harm and side effect to the patient.

What are the health concerns regarding the methylglyoxal?

Methylglyoxal though is very beneficial but there are many studies which show negative effects of the methylglyoxal. Methylglyoxal can also be very toxic if not used properly or exceed in its dosage.

It can induce neurodegenerative disorders

Various neurogenerative disorders are caused by the methylglyoxal consumption, which include both minor and some symptom of major disorders like Alzheimer. In the patients suffering from Alzheimer the quantity of methylglyoxal was found to be very high in brain as compared to the normal person.

This accumulation of methylglyoxal in brain of Alzheimer patients was seven times more than the normal person and is responsible for toxicity.

Yang G et al in their study found that high concentration of methylglyoxal in diabetic mother can induce neural disorders in the offspring. The premature development of brain in child leads to changes in neural precursor cells and hence brain development got affected.

What does this mean?
Methylglyoxal can be toxic for the neural cells and can even damage them. It can be the cause of various types of neuro degenerative disorders.

It can induce diabetes

Diabetes is a very common disease these days. It affect complete metabolism of the body. The concentration of various sugars in the blood becomes high which leads to development of several other symptoms.

It has been found that methylglyoxal content is increased to several folds in the diabetic patients which lead to further complications like insulin resistance, vascular dysfunction and neural diseases.

Juraj Majtan in his study explains the harmful or delaying effect of methylglyoxal in Manuka honey on diabetic foot ulcers. In his study he found that methylglyoxal help in bounding of glucose to the protein and production of advanced glycation end product (AGEs).

These AEGs with Methylglyoxal later impair the wound healing activity of body.

Another study conducted by Berlanga J et al on rats gave similar kind of results. In this study, rats were exposed to methylglyoxal which results in delayed wound healing and microvascular damage (damage to small blood vessels and capillaries) and also induces some diabetes like complications.

What does this mean?
Methylglyoxal is the precursor of many glycation products. It decrease the glucose absorption by cell and hence blood glucose level increase which leads to diabetes.

It can induce oxidative stress and aging

Methylglyoxal is also associated with the aging of the person. It has been found in many studies that the accumulation of methylglyoxal in the body is very toxic and can induce early aging and oxidative stress.

Maessen DE et al study the role of methylglyoxal in diabetes and age related disorder. They found that methylglyoxal affect various biochemical pathways which are involved in age related diseases.

What does this mean?
Methylglyoxal is responsible for early aging and oxidative stress.

It may cause mitochondrial dysfunction and apoptosis (cell death)

Mitochondria are very essential part of any cell machinery. It prepares and store the energy require for all the functions of the cell.

It has been found in a study that methylgloxal affect the reactions which takes place in the mitochondria of brain cells of rats and affect the energy requirements and their fulfilling efficiency i.e. whole bioenergetics of the system is affected.

Apoptosis is a natural process which takes place in body without even any external influence but it has been found that methylglyoxal stimulates the process of apoptosis in the pancreas and also damage the DNA of the cells present there.

What does this mean?
Methylglyoxal is known to increase the speed of natural process of cell death and also affect the energy requirement of cell by affecting mitochondrial activity.

It can induce IBS

Methylglyoxal is also known for inducing the irritable bowel syndrome (IBS). Shuang Zhang et al in their study on rats showed that if rats are exposed to the

Manuka honey they show symptoms like diarrhoea, headache, depression and anxiety. These symptoms later worsen and develop in to IBS.

What does this mean?
Methylglyoxal can also induce the symptoms like upset stomach, diarrhoea associated with irritable bowel syndrome.

It may destabilize hemoglobin

Haemoglobin is the most important component of blood as it helps in exchange of air between lungs and rest of the body.

But it has been found in a study that methylglyoxal affected the structure of the haemoglobin. Banerjee S and Chakraborti AS conducted a study to see invitro effect of methylglyoxal on haemoglobin.

They incubate haemoglobin with methyglyoxal honey for 1 week at 25 degree C. The result shows changes in protein component of haemoglobin which affect its binding ability with iron and with other components.

What does this mean?
The methylglyoxal modify the haemoglobin both structurally and functionally which bring physiological changes in body.

How much methylglyoxal does Manuka honey contain?

Manuka honey is known for its high methylglyoxal content. Manuka honey has 100 times more methylglyoxal content than any other conventional honey. Mavric E et al in their study find out the methylglyoxal content of six samples of Manuka honey.

They found that Manuka honey contains 38-761 mg/kg of methylglyoxal in it.This concentration is quite high if compared to other honeys.

Methylglyoxal in Manuka honey is produced by conversion of dihydroxyacetone in to methylglyoxal over a period of time at 37 degrees C. This dihydroxyacetone is present in the pinkish white flower of Manuka tree. Also the high pH and amino acid content favour the formation of methylglyoxal.

Is the methylglyoxal found in manuka honey safe for health?

Though it has been found that methylglyoxal is both beneficial and toxic for the human from the above-mentioned evidence. But when question arise on the safety of methylglyoxal in Manuka honey most of the studies have shown positive results.

All the studies which show toxic effect of methylglyoxal are mostly conducted on the methylglyoxal as a separate component and not as part of Manuka honey. Some which uses Manuka honey for test and yet show some negative are based on animal systems and that too no highly adverse effect is reported in any study.

So based on the above data it can be concluded that the amount of methylglyoxal is safe in Manuka honey for the consumption by a healthy individual.

Diabetes patients need to be a bit careful while using Manuka honey.

Also, it is highly recommended to keep a check on the quality of the Manuka honey which can be easily known by the UMF value of the Manuka honey. As different Manuka honey lot have a varied range of methylglyoxal in them so UMF (unique Manuka factor) helps to keep a check on it.

UMF also keeps a check on the concentration of Manuka honey as at low concentration Manuka is safe to use but at very high concentration (more than 50%) it might show some toxic effect.

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