Tuesday, 10 November 2015

As far as conspiracy theories go, this is a good one!

2015 Jun 25. pii: 1352458515591862. [Epub ahead of print]

Why does multiple sclerosis only affect human primates?

Abstract

BACKGROUND:

Multiple sclerosis (MS) develops exclusively in humans. Non-human primates are resistant against MS, although they are highly susceptible to the MS animal model, experimental autoimmune encephalomyelitis (EAE). Unravelling of the cause(s) underlying this discrepancy is highly relevant as insights might be gained into the elusive event(s) that trigger(s) MS. A well-established difference between the human primate (Homo sapiens) and non-human primates is that humans are unable to synthesize the sialic acid N-glycolylneuraminic acid (Neu5Gc).

VIEWPOINT:

We propose the concept that long-term ingestion by human primates of the foreign Neu5Gc, via red meat consumption, is an ignored environmental risk factor for MS. Conceptually, incorporation of dietary Neu5Gc into vital regions of the central nervous system, such as the blood-brain barrier (BBB) and the axon-myelin unit, creates targets for binding of de novo synthesized heterophilic anti-NeuGc antibodies. Binding of the antibodies can cause BBB leakage and destabilization of the axon-myelin coupling. The ensuing cytodegeneration and release of self-antigens could be a start of the characteristic pathological features of MS.


Professor Hart is clearly going out on a limb here, none of his colleagues have deigned to join him in co-authoring this manuscript. However, I like to form my own opinions and have come to the conclusion that another theory wouldn't go amiss in the long list of plausible explanations for MS.

Hart raises a valid question, which is why MS develops spontaneously in humans (which he calls human primates), but not in related non-human primate (NHP), such as the chimpanzee? Now chimps share a genome that has >98% genetic similarity to us - ergo are very similar to us in their immune system, and breathe the air that we breathe, and live in the temperate climes linked to high rates of MS. Now NHPs don't smoke, but they do develop a chronic latent infection with EBV-like viruses and their hairy pigmented skin is not conducive to vitamin D production - and yet no MS.

So what does Hart suggest? He proposes a new candidate, Neu5Gc (N-glycolyneuraminic acid) as the culprit in triggering MS. Neu5Gc is found at the end of most glycoproteins in our bodies, but is absent in the CNS, where its production is supressed and its expression here may be detrimental. Humans unlike NHPs cannot synthesise Neu5Gc on their own; a change which took place around 3 million years ago in the hominoid lineage. But when human tissues are studied, it is present. The main source for this, therefore is in the diet, in particular from red meat (beef, pork, lamb). He further suggests that there is strangely an overlap between the global MS risk and areas with high intake of meat from livestock as part of their daily diet. 

Hart may have a point, but can we prove this? By probability alone there is a 50/50 chance that the answer to this question is a YES. 

23 comments:

  1. How many people with MS are vegetarians and don't eat meat a large number I suspect .

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    1. And yet EBV infects more than >90% of worlds population but prevalence of MS is 2.5 million. The odds of lung cancer in smokers relative to non-smokers is 40; majority of MS risk factors struggle to reach an odds of 3. The seasonal variation theory flounders at 1.0.

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    2. EBV infects >90% of the population but only gives a small number of people a year mixed cellularity Hodgkin's Lymphoma. That fact that it is rare does not stop it doing it.

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    3. NHP don't breathe the same air. How many of us non smokers were subject to passive smoking in childhood. Didn't meat eating contribute to brain development and intellect in humans? Or have I got this completely wrong?

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  2. "By probability alone there is a 50/50 chance that the answer to this question is a YES. "

    I think that you may misunderstand how maximum entropy priors work. If you apply this procedure in general (assigning unknown propositions 50/50 probability), you will not give you a consistent probability distribution.

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    1. A hunch would you not agree is 50/50, can you apply a mathematical principle to this? When there is no empirical knowledge wouldn't the maximum entropy match our intuitions?

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  3. I know that many patients with MS or to adopt a vegetarian diet based on fish intake and eggs tend to have a "better" course of the disease, whether that use DMT...
    Based on this hypothesis, in Brazil consumption Red Meat is also very high. You have likely heard of the "churrasco, or Brazilian meat carvery". We would have here then an epidemic of MS. Certainly the cases doubled disease 20 years now, but the data that the Brazilian Ministry of Health (to be said in passing is a source that leaves much to be desired) continue to point that even with the growth of the disease among Brazilians to rate remains lower than those of other countries most affected ...
    But perhaps the presence of Neu5Gc (N-glycolyneuraminic acid) to which it has genetic factors for disease is not a good idea ...


    By the way where that fits the cases of monkeys in Oregon and the Japanese monkeys with a kind of spontaneous encephalomyelitis similar to MS?

    http://www.ncbi.nlm.nih.gov/pubmed/21674589

    http://www.medpagetoday.com/Neurology/MultipleSclerosis/27378

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    1. Interesting about the non-human primates.

      The Japanese macaques in the study you mentioned are a captive colony and not wild primates. All those affected by the MS-like disease had two things in common, that their unaffected colony mates did not share:

      1. They were descended from a specific maternal lineage
      2. They were all infected with a novel gamma-2 herpes virus.

      Although they are omnivorous, I very much doubt they are fed a red meat/dairy diet in captivity - although I could be wrong.

      I have serious doubts about the red meat theory in humans, but I kind of like it!

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    2. I suspect a load of Double Dutch

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    3. Susceptibility isn't the issue, as we know from EAE you can induce the disease. But in nature, MS appears to be rarity in other primates and animals. Humans are at the top of the food chain for one reason...

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    4. Are there any progressive neurological disorders in 'nature' that aren't acquired?

      Genetic predisposition to the development of neuro disorders at reproductive age of would have been removed from the gene pool of wild populations, or is that what you are saying?

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    5. Animals do acquire other neurological autoimmune disorders similar to humans - so there is the myaesthenic horse ("equine shivers"), and dogs with systemic lupus erythematosus with neurological complications. In answer to your second comment, I don't know. Domestic animals are in-bred and you'd think they would be more susceptible.

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  4. I have been pescetarian (vegetarian and fish only) since aged 13 and was diagnosed RRMS aged 38. May be the lack of red meat in my diet helped the MS be very benign until then. Since my MS diagnosis I have added a little poultry to my diet.

    I moved away to become a postgrad not long after a nasty head injury and got very anxious and stressed then got an infection. Then my first MS symptom appeared.
    I think for me there was a tipping point, a threshold. All these events happening so close to each other was too much on my immune system. Though I did have a numb tongue for around 10 seconds when I was aged 25.

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  5. "and their hairy pigmented skin is not conducive to vitamin D production" boldly assumes it is made in the skin not in the oils on the fur.

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  6. While it would not surprise me if red meats are a piece in a puzzle if it were a primary factor the USA would be a giant exacerbation (physically, metaphorically eh?). While Ape's do share quite a bit with us so do other mammals. Atop this the amount of human research far outweighs that of research on ape's in a clinical format. Some say its the proteins in red meats that resulted in intelligence moving a head (lol) at an accelerated pace. On the other side is interventions as well as intelligent design.

    Its an interesting hypothesis but at this point pursuing it be like voting for Trump, scary.

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  7. But other primates do eat red meat.

    Sorry I'm not in a position to try to be more eloquent at the momen

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    1. Your're correct! No theory is without flaws.

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    2. Yes - I'm no Jane Goodall, but I have seen BBC film footage of chimpanzees literally tearing an animal apart to then eat it.

      https://www.youtube.com/watch?v=A1WBs74W4ik

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  8. The red meat consumption is very high in both Argentina and Uruguay buth neither of them is considered to be high risk areas.. They do have a lot of sun.

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  9. Dear NDG,

    I enjoy your 7pm Monday post every week, but this one is my favourite so far. Did not get a chance to post last night. Thanks!

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    1. Yes love reading your comments NDG - thanks for contributing!

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