Understanding and Comparing Immunomodulators

There is a lot of misunderstanding as to what immunomodulators actually are

Immunomodulators are becoming very popular in the worldwide natural health industry as people start to realize the importance of a healthy immune system in the maintenance of health and the prevention and recovery of disease. Help the immune system, and the body helps itself — often quite considerably.

However, there is a lot of misinformation circulating about these natural compounds, much of it put out by companies trying to sell their particular immunomodulator. There are even many doctors who are misinformed about the action of these compounds. Here we take a glance at immunomodulators and how to compare them.

What is an immunomodulator?

An immunomodulator is any substance that helps to regulate the immune system. This "regulation" is a normalisation process, so that an immunomodulator helps to optimise immune response. Give an immunomodulator to someone with a low immune system, and it can help raise that immunity; give a modulator to someone with a healthy immune system, and it will have little effect in the body; and give a modulator to someone with an overactive immune system, and can help to normalize that overactive immune system.

So immunomodulators do not tend to boost immunity, but to normalize it. This is why, looking at some of the research data on Biobran MGN-3, you will notice that those with stronger immune systems got relatively less immunomodulation with the product than those with weak immune systems.

How do they work in the body?

How immunomodulators work in the body is still largely a mystery. Part of their benefit appears to be their ability to naturally increase the body's production of messenger molecules, such as cytokines, which mediate and regulate the immune system. Some of them, like Biobran, can also decrease the production of inflammatory cytokines. Overall, the effect is a more efficient immune system.

Most people using substances like Biobran MGN-3 do so because they have low immune systems. Increasing cytokine production in this case can significantly help raise the immune response. This site focuses, therefore, on the effect of immunomodulators in helping to increase immune function.

A Standard Immunomodulatory Response

Below you will see s graph depicting the effectiveness of a typical immunomodulator at three different arbitrary dosages on individuals with low immune systems.

Fig 1: Typical Modulator Response with Dosage

 

You will notice that, after a period of time on a particular dose, this typical modulator modulates the immune system to a characteristic level that is independent of dosage (provided of course we are dealing with effective dosage ranges). The difference between dosages is that higher doses tend to modulate quicker, and although the difference might only be small, as in this case, it is very significant to those who are seriously unwell and need immune system help as fast as possible.

After a period of time, there is little benefit staying on a high doses, which is why lower "maintenance" dose are usually recommended. That is why, in the case of Biobran MGN-3, individuals who take the high 3g a day dose usually come down to 1g a day after a two month period — remaining on 3g a day after that time is not conferring any extra benefit (and costs three times a much!).

Below we see an actual graph of MGN-3 modulation with dosage. There are too few data points to make a nice smooth graph, and because of the small sample size used to compile the graph the 1g dosage ends up slightly higher than the 3g dosage, but give a large enough sample the modulatory signature of MGN-3 with dose would match the smoothness of the graph above.

Fig 2: 3g (dot dash), 2g (dots) & 1g (line) dose comparisons of MGN-3 with NK cell activity (data from Maeda / Daiwa Pharmaceutical)

The mistake many people make is to assume that dosage and effectiveness is additive, in other words, double the dose and you double the benefit to the immune system. This is incorrect as you can see from the research. In fact, after a period of time, doubling the dose does not give any extra benefit.

Examples of Misleading Comparisons

In a market with many different immunomodulators, each one vying for market share, there are many instances when different products have been compared in a misleading way. Sometimes this confusion is unintentional, showing a lack of understanding of the non-linear nature of modulators, and sometimes it is intentional as it is often the only way less effective immunomodulators can market themselves. Here are a couple of real life examples of misleading comparisons:

AHCC® and Biobran® MGN-3:

Those selling AHCC® often claim that it is a better supplement because, as it is a cheaper product, more can be taken to make up for its lower effectiveness. But as both AHCC® and Biobran are immunomodulators, one can see from the general characteristics of immunomodulators that just taking more of one does not necessarily increase its overall value in the body. Even some doctors have made the mistake of assuming that doubling the dose of an immunomodulator doubles its effect in the body. This is plain wrong. (See the AHCC® comparison page.)

Noxylane4™ and MGN 3®:

In 2004, Lane Labs started selling a new product called Noxylane4™ which was just their usual MGN 3® (their brand of Daiwa's MGN-3) with a tiny bit of seaweed extract added to it. They claimed that the seaweed extract increases the absorption of the MGN-3 to the point where 2g of their new Noxylane4™ was equivalent to 3g of their usual MGN 3®. This statement, however, is misleading because it gives the impression that Noxylane4™ is more potent than the standard product so that you only need two-thirds the dose to get the same effect. In fact, as you can see from the graph above, 2g of MGN-3 will give a similar immunomodulatory effect to 3g of the MGN-3. So the comparison is meaningless. (A meaningful comparison would have been 2g of Noxylane4 with 2g of MGN-3.) Noxylane4™ presents a classic instance of how the non-linear nature of immunomodulators can lead to confusing and misleading comparisons. This product was temporarily withdrawn when Lane Labs had problems with the FDA over MGN 3®, but it once again appeared in Feb 2005.

Conclusion

Immunomodulators are going to be a central part of 21st medicine. Helping the body help itself by optimising the immune system is of central importance in a society so stressed, unhealthily nourished and exposed to toxins that most of us are likely to have compromised immune systems. Immunomodulation, however, is a normalizing process, and it is important to bear this in mind when choosing doses over time and comparing different products.

Biobran and MGN-3 are both registered trademarks of Daiwa Pharmaceutical, Tokyo, Japan