Tuesday, 4 October 2011

Research News & Bad Media: Glucosamine-Like Supplements

(Mouse) Doctoring the News.
This weeks news story, which has recently surfaced is:


"Dietary Supplement Suppresses Attacks In MS"


So before rushing down to Holland and Barrett to stock up on more Nutriceuticals lets look at the story.

Again it is firmly embedded in Mouse Biology and has nothing to do directly with MS and reports on a paper by Grigorian A, Araujo L, Naidu NN, Place D, Choudhury B, Demetriou M. N-acetylglucosamine inhibits T-helper 1 (Th1) / T-helper 17 (Th17) responses and treats experimental autoimmune encephalomyelitis. J Biol Chem. September 29, 2011

But first you may remember that genes code for amino acids that produce proteins. However, these proteins may be modified after production to contain carbohydrates by a process called glycosylation, which influences the structure of the protein.

If we go back to the same journal a few years ago (J Biol Chem. 2007;282:33725), the same group reported the development of a so-called Spontaneous Model of Multiple Sclerosis in mice that lacked N-acetylglucosaminyltransferase genes called Mgat5. This can glycosylate certain sugar-like molecules (N-acetylglucosamines such as those found in shrimp shells) on proteins and these N-acetylglucosamines can influence immune function. Lack of the Mgat5 gene could eventually trigger kidney disease in one mouse strain, but neurological disease occurred in another strain of mouse. This was claimed ("in my humble opinion-total rubbish") to be a spontaneous model of progressive multiple sclerosis. (The disease was a polyneuropathy-[disease of both the central and peripheral nervous systems], which is not typical of multiple sclerosis that usually is restricted to the central nervous system). Nevertheless this suggested that these gene products may influence the self-destructive potential of the immune system, depending on the genetic background of the individual.

Although genetic analysis of susceptibility in multiple sclerosis have yet to really point a definative finger at N-acetylglucosaminyltransferase genes, it has been suggested that the genetic variants of some immune genes (such as those influenced by vitamin D), which have been shown to contribute to susceptibility to MS, could influence the activity of MGAT molecules. This influences the glycosylation of molecules involved in the immune function of white blood cells associated with the development of relapsing MS. (Nat Commun. 2011;2:334).

These studies combined with some previous data in models of diabetes suggested that supplementation with N-acetylglucosamines may be able to inhibit immune function in the EAE model of MS, which is the story in the news!

This new study suggests that dietry supplementation of drinking water with N-acetylglucosamines augmented the recovery from neurological disease in mice with an MS-like disease. This coupled with previous studies in autoimmune diabetes suggests that these molecules have the potential to inhibit the immune responses that drive clinical attacks.

However, the experiments were not designed such that they could really show a treatment effect on relapsing disease. The degree of disease control was not particularly startling, compared to many other drugs we have used, although the way the drugs were used (treatment at disease onset with a believed time to effective dose of one week) it was amazing that they were shown to do anything and indeed the supplementation failed to curtail aggressive disease. Furthermore some bits were not very believable given the woefull underpowering of the experimental groups (n=4), such that it should not be possible to get the level of effect (P<0.0001) reported. (P<0.0001 one in ten thousand chance that this result observed would occur by chance. With groups sizes of 6 verses 4 animals the maximum statistical difference would be P<0.01. One in a hundred chance).


On the plus side, efficacy was found in the dose-range in which such supplements are used in humans and so it is not a case of needing to take a "tub-of-lard" to be in the effective dose-range as found with some nutriceutical fats. However, as is every the case there is no evidence that these will work in human MS and they will not be recommended until their benefit is formaly shown.

The authors of the new study say "That clinical trials are warranted". Whilst this may be so, as the authors have built up a working mechanism of action, it should be easy to demonstrate this action by examining cells in the blood this within a few weeks of treatment. Therefore one should not need to take years undertaking clinical trials to determine whether this idea is put to the sword or not.

These supplements are used by many with joint conditions and if it had a really marked immunosuppressive action, surely one would think that this activity would be known. Therefore, I am not expecting a cure with this, and it may be better for relapsing MSers, if it is active.

So let's be optimistic, but also let's be realistic. We have been here before and many things have bitten the dust. Let's hope not.

3 comments:

  1. As with all drugs, there are always potential side-effects associated with their use. However being a nutriceutical, there is not enough information known about safety. These agents are widely available. But I'll leave it to Prof G to give medical advice.

    If it were such a great immunosuppressive there would probably be risk of dampening down your immune system, and could make Asthma worse if the mechanism of action is correct.

    And finally the risk is spending even more money on something of unproven efficacy.

    ReplyDelete
  2. Glucosamine is good for the
    aches and pains I get when training. I feel you have to take it for a month or
    two before you start to really notice the benefits though.

    ReplyDelete

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