Friday, April 17, 2015

Magic Mushrooms!

Just read a nice review of a new study on Medical Express, Mushrooms boost immunity, by Brad Buck.
"Pholiota limonella" on a willow tree (not edible, possibly hallucinogenic) (Photo by me)!
 If you eat a shiitake mushroom every day, you could see changes in their that are beneficial," said Percival, an Institute of Food and Agricultural Sciences faculty member. "We're enhancing the immune system, but we're also reducing the inflammation that the immune system produces.

The full text of the study is not yet available, but here is the abstract:  Consuming Lentinula edodes (Shiitake) Mushrooms Daily Improves Human Immunity: A Randomized Dietary Intervention in Healthy Young Adults

In the study, they gave 52 healthy people, aged 21-41 years old, either 5 or 10 grams of dried shiitake mushroom daily. After 4 weeks blood tests confirmed exceptional boosts in their immune system.

Eating L. edodes for 4 weeks resulted in increased ex vivo proliferation of T (60% more, p < 0.0001) and NK-T (2-fold more, p < 0.0001) cells. Both cell types also demonstrated a greater ability to express activation receptors, suggesting that consuming mushrooms improved cell effector function. The increase in sIgA implied improved gut immunity. The reduction in CRP suggested lower inflammation. The pattern of cytokines secreted before and after mushroom consumption was significantly different; consumption resulted in increased interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-α, and IL-1α levels, a decreased macrophage inflammatory protein-1α/chemokine C-C ligand 3 (MIP-1α/CCL3) level, and no change to IL-6, IL-1β, MIP-1β, IL-17 and interferon (IFN)-γ levels.

I'm curious to see the full text and to what the researchers attribute these positive changes.  These mushrooms are rich in beta-glucans and chitin, both types of fiber, and also polyphenols and loads of other chemicals with antifungal, antitumor, antiinflammatory...blah, blah, blah (they are good for you!).

Edible mushrooms I picked last summer in my backyard


And, it seems, all mushrooms are just about equally good for you:  white buttons, portobello, oyster, and shiitake are commonly found in the supermarket.  Locally, wild mushrooms like morels, shaggy manes, and many others can be free for the picking.  As it's Spring, and mushroom season almost everywhere, do yourself a favor and learn the local 'shroom scene.

Fresh morels, lightly sauteed in butter
 There is no reason to limit mushrooms, in fact a serving or two most days is probably just right.

Later!
Tim

 

151 comments:

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    1. By Jove, I think she's got it! I thought it was a fly agaric (Amanita muscaria) as they were all around on the ground near this one, but the color was off a bit.

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  2. I did some reading on mushrooms a while back. Everything you say here resonates with my thinking. Because it is hard to find more than three or fours types of mushrooms in the grocery stores, I've started taking Host Defense MyCommunity (love the word play) that has about 17 different types. I pop a few other dried types here and there, and eat fresh ones when I can, several times per week. I don't know if diversity matters, but it's what I do.

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    1. I forgot to add that i really became interested in mushrooms after reading one of Jared Diamond's books. He was stuck with a New Guinea tribe with no food. The tribe went out collecting mushrooms to eat. Diamond freaked out, wondering if the mushrooms were safe. The tribe laughed at him, saying that knowing safe from unsafe mushrooms is part of their knowledge. It's probably been that way for a very long time.

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    2. One thing I learned about cooking mushrooms: If you want them to be beautifully golden browned, heat oil, butter, or ghee in a pan to medium hot. Put the mushrooms in in a single layer and do not touch them for three minutes. If you move them, they will release water and not brown (as well). Then flip them and cook until done. I learned this from the cookbook Ad Hoc at Home. They come out perfect every time. FWIW

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    3. I think I will test your theory right now, sir! I have a box of brown crimini mushrooms, which are actually baby portobellos, BTW, that are going in my scrambled eggs this morning one way or another.

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    4. Did it work for you?

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    5. Wilbur, you mean put the mushrooms on their backs first. Fresh shitakes I leave like this until the edges start to get a bit crunchy, salt the gills and then flip. Really brings out the flavour.

      Creminis are always less wet than white mushrooms. They really pump those white ones up. And if you leave them in a paper bag in the fridge for a, ahem, month, they start to get dry..... the creminis do. Then they don't make a mess. White ones just rot. Too wet.

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    6. See, this is why I'll never be a cookbook author: I forget important details. I nearly always slice my mushrooms, and the method I describe is for sliced mushrooms. It might work for mushrooms cut differently, but I don't know.

      I don't now if it works for reconstituted mushrooms. It has worked for every type of (sliced) fresh mushroom for me.

      But yeah, the main idea is that keeping them still will prevent the water from being released. If the water gets released, then the max cooking temp is 212F, below what is needed to brown them. In essence, they become boiled rather than browned.

      This method even works on sliced white button mushrooms.

      One of my favorites is grilled portabella sandwiches. Especially with a nice pesto.

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  3. BTW, your link does go to the full study, interesting stuff - but some cytokines increased, others decreased, I don't think anyone can say what is good or bad, since the same cytokine can be pro inflammatory in one circumstance and anti-inflammatory in another.

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  4. Tim, Since anti-aging therapeutics often benefit the immune system, your highlighting the immune system benefits of mushrooms caused me to Google for anti-aging effects and I found some, including some rather unusual ones: http://www.webmd.com/balance/news/20110929/magic-mushroom-drug-anti-aging-effect-personality

    - PaleoPhil

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  5. Tim, thanks so much for citing this article about the immunomodulatory effects of Shiitake mushrooms. There are many such studies on different varieties of mushrooms on immune-compromised people, especially cancer patients. They generally show somewhat positive immune effects (increased NK cell activity, higher WBC components, lower TNFa) on cancer patients but minor effects on healthy poeple. Probably the most widely studied are Reishi (Lingzhi) mushrooms used in Chinese medicine and turkey tail mushrooms, which are known to improve immune benchmarks somewhat.

    http://examine.com/supplements/Ganoderma%20lucidum
    http://examine.com/supplements/Trametes%20versicolor

    There are supplements available as Ganoderma lucidum extracts or Reishi mushroom extracts:

    http://www.swansonvitamins.com/q?kw=reishi
    https://www.google.com/#q=reishi+extract&tbm=shop

    Similar points have been made about garlic, especially Aged Garlic Extracts (AGEs). I don't take Reishi extracts but do take AGEs, which have minor immune-boosting effects on healthy (not just sick) populations.

    http://examine.com/supplements/Garlic

    Garlic is better known for helping you fight off cold and flu symptoms by improving NK and T cells functioning.

    http://examine.com/rubric/effects/view/564/Natural+Killer+Cell+content/all/

    Along with 1.2 grams of AGEs every day, I also follow Ray Medina's raw garlic protocol where I slice 1-2 cloves of garlic, dice them to get the "allinase" activated, put them in a glass of water mixed with 1 tsp of apple cider vinegar and drink 2-3 hours before going to sleep.

    http://gutcritters.com/why-raw-garlic-may-be-your-guts-best-friend/
    http://gutcritters.com/small-intestinal-bacterial-overgrowth-part-eight-treatment-options-for-sibo/

    Been about 1.5 years. Despite my immune compromised status, no cold, flu, sinusitis, or respiratory infections in the last 3 years. It's not solely because of the garlic of course; I keep my Vit D3 at 50-70, take 1.5g of Vit C everday, along with turmeric in my lentil/bean soup everyday, in addition to taking flu/pneumonia shots every Fall.

    One impressive thing was when just about everyone around me had a cold, I only came down with a semi-sore throat one evening and my body fought off the other symptoms and the sore throat was gone the next day. Could be the garlic, Vit D, flu shots, Vit C or the placebo effect from all of the above. Something which I think every person who became immune-compromised after VLCing medium- to long-term should consider to stave off potential problems down the road. Especially if your WBCs and Globulins are declining.

    Span_Carvan

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    1. Nice! I like your routine. We have been talking about the benefits of crushed garlic around here, too. Definitely something to add to one's daily eating plan.

      Did you notice the white 'coral' looking mushroom in the picture above? It's a Hericium erinaceus, or Lion's Mane, maybe one of the most powerful of the edible mushrooms.

      Neuroregenerative potential of lion's mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (higher Basidiomycetes), in the treatment of peripheral nerve injury (review).

      "The aim was to explore the possible use of this mushroom in nerve repair." (It seemed to work!)

      Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake.

      " Our results show that HE intake has the possibility to reduce depression and anxiety and these results suggest a different mechanism from NGF-enhancing action of H. erinaceus."

      Hericium erinaceus (Lion's Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-tansplanted mice.

      "Dietary administration of HWE and MWE reduced the formation of tumor nodules in the lung by about 50% and 55%, respectively, and prevented increases in lung weight caused by cancer cell metastasis."

      I see it's available on Amazon, but I can usually find a couple big bunches every summer near home. It's not very prolific, and it's short-lived, but it comes back every year in the same spot if the weather is right. It's also very easy to identify with no 'lookalikes' that are poisonous. It supposedly grows all over North America, Europe, and Asia on fallen logs and can even be cultivated.

      Next batch I cook up will have some crushed garlic!

      Cheers

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    2. Exactly, Tim. That Lion's mane mushroom is also big in Chinese and Oriental medicine and you can buy them from Asian grocery stores in big cities like San Francisco. Known as "deer rear-end" mushrooms in parts of Asia because it looks like a big chunk of a deer's rump rather than mushrooms.

      Looks like Examine.com has to update their research table on Lion's Mane (aka Yamabushitake, etc.), as those 2 studies are missing.


      http://examine.com/supplements/Yamabushitake

      People who practice Oriental medicine really believe in these mushrooms. For example, some amelioration of dementia and Alzheimer's albeit temporarily (4 weeks), similar to the expensive IV glutathione therapy that Dr. Perlmutter administers on his patients:

      http://www.ncbi.nlm.nih.gov/pubmed/18844328

      You can probably do it at a fraction what Perlmutter charges. Both have temporary but palliative effects that are considered to be powerful or minor depending on who you talk to. Also, some positive immune effects on T/CD4+ cells when applied to lung-cancer cultures and faster wound-healing in rats:

      http://www.ncbi.nlm.nih.gov/pubmed/11842649
      http://www.ncbi.nlm.nih.gov/pubmed/22135902

      The slow wound healing phenomenon is probably the clearest sign that you've been negatively affected. I saw that while VLCing as my skin dried / thinned out and my paper cuts were taking forever to heal. It's part and parcel of dysregulated cortisol and other hormones, which always have immune effects.

      Spanish Caravan

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    3. I was inspired some months ago by Jeff Leach's writings to eat more strong-tasting roots raw, like garlic, onion, leeks, shallots, ginger, etc. I'm curious whether it will improve my below-avg stomach tolerance of raw onion. I even found fermented garlic at Trader Joe's (which I'll bet contains the active ingredients in the aged garlic extracts mentioned above), which was mild, sweet and tasty, and thus easier to digest, though too expensive to make a regular purchase.

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    4. Fermented Garlic = Black Garlic? I tried the black garlic recently. It tasted like jellybeans. I've also tried lactofermented fermented garlic and found it was easy to make and lasts for a while. Smooth tasting and not spicy at all.

      Barney

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    5. @Span_Carvan

      Interesting tips. However, I am wondering if it is wise to use vitamin C as supplement. I think it is much better from real foods.

      Also, regarding "autoimmunity", and previously mentioned Wahls: have you also removed milk from your diet? No matter if you are (genetically) lactose tolerant?

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    6. Yes, the label says "Sweet & Mild {fermented} Japanese Aomori Black garlic." It was the "fermented" that caught my interest, though it is disputed whether it is truly fermented or not. It is not to be confused with Middle Eastern unprocessed black garlic (Allium nigrum).

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    7. Gemma, food is always preferable but Vit C is supposed to be water-soluble and non-toxic. I take it as insurance in divided doses three times a day since I don't drink juice or eat much fruit for that matter, in addition to fighting off potential infections to which I may be vulnerable given my status.

      As for dairy. Yes, if you have autoimmune issues, you should avoid gluten, dairy and egg whites. Anything after that like nightshades and legumes should be carefully vetted. Dairy is an issue for potentially 3 reason: (1) it's a simulacrum of gluten proteins in people with intestinal permeability; (2) it's a common allergen to which sensitive people react; (3) it has Neu5gc which has proven to be inflammatory to at least 1 most common autoimmune issue, i.e., Hashimoto's. I've long wondered why those who join Paleo and start eating heavy redmeat see their antibodies skyrocket. It turns out Neu5gc in redmeat and dairy are actually better prognisticators of Hashimoto's than the antibodies, TG and TPO, themselves. I'd avoid redmeat and dairy, in addition to gluten and egg whites, if I have Hashimoto's:

      http://perfecthealthdiet.com/2015/02/neu5gc-autoimmunity-hashimotos-hypothyroidism/

      Food avoidance isn't something invented by Wahls or the AIP. It goes back many years to the vegetarians and vegans with autoimmune issues, who saw their symptoms improve by avoiding them. It will be at least palliative for most people with autoimmune issues. That portion of the Walhls protocol is in fact valid and time-tested.

      Span_Carvan

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    8. For those who can't eat mushrooms without adverse gut consequences: there are people with trehalase deficiency. Consuming mushrooms results in the same symptoms as when people with lactase deficiency drink fluid milk.

      So if mushrooms give you bloat, gurgling guts, diarrhoea.... this is why.
      http://www.ncbi.nlm.nih.gov/pubmed/10522609
      http://rarediseases.info.nih.gov/gard/10372/trehalase-deficiency/resources/1

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    9. @Gab

      Trehalase deficiency is extremely rare in most populations, but surprisingly there is a very high incidence in Greenland (one study found 8%).

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    10. @Gemma: just for the Greenlander readers of this blog. :) :)

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  6. @Span_Carvan

    "Yes, if you have autoimmune issues, you should avoid gluten, dairy and egg whites."

    Yes, the autoimmune diet protocol is quite long and many people eliminate even many more foods and at the end are left with almost nothing to eat.

    The actual question of autoimmunity rather is: what the hell it is, and why there is defective clearance of NETosis / apoptotic bodies.

    Re lactase and lactose: I have in fact asked if you know for sure that you are also lactose intolerant, meaning your intestines do not make the lactase enzyme. Just wondering...

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  7. Gemma, depends how serious your symptoms are and whether you think it's worthwhile. I agree with you, most people eliminate way too many foods and their food choices then become unreasonable. Plus they develop false associations. But at the top is always gluten and dairy. You start from those two if you have autoimmune symptoms.

    Dairy sensitivity in the context of autoimmunity is not the same as lactose intolerance. It's usually "sudden onset," unlike lactose intolerance, and you may have tolerated lactose all your life. Plus you may not realize your autoimmune symptoms worsen when you eat dairy. Among people I know, I don't know a single person whose autoimmune symptoms didn't improve upon removing dairy. Most such people had Hashimoto's. I have RA and my symptoms worsen significantly when I eat dairy. And I practically grew up on Cocoa Puffs and Vitamin D milk, so I wasn't lactose intolerant. Span_Carvan

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    1. Thanks for your answer. I am in fact VERY interested in lactose (and lactase persistence into adulthood, respectively) after reading this paper:

      Lactose in Human Breast Milk an Inducer of Innate Immunity with Implications for a Role in Intestinal Homeostasis (2013)

      "Postpartum, infants have not yet established a fully functional adaptive immune system and are at risk of acquiring infections. Hence, newborns are dependent on the innate immune system with its antimicrobial peptides (AMPs) and proteins expressed at epithelial surfaces. Several factors in breast milk are known to confer immune protection, but which the decisive factors are and through which manner they work is unknown. Here, we isolated an AMP-inducing factor from human milk and identified it by electrospray mass spectrometry and NMR to be lactose. It induces the gene (CAMP) that encodes the only human cathelicidin LL-37 in colonic epithelial cells in a dose- and time-dependent manner."


      If anybody happens to have some thoughts, I'd like to hear them.

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    2. Spanish, that is exactly what Gemma and I are looking for: dysfunctionality in the gut immune system in lactase persistors and auto-immune disease.

      In babies, lactose is a positive for developing a competetent immune system. Possibly in those who are lactase persistors does gluten (because they are non coeliacs) then become the Trojan Horse somehow triggering a cascade in vulnerable individuals?

      Fasano says that there are 6 known genes for Coeliac susceptibility. Doesn't mean they will develop Coeliac unless it is somehow triggered.

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    3. @Spanish
      What about kefir, is that still considered dairy? Meaning if you have auto immune issues, it should be avoided?

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    4. I'm another person who grew up on a diet heavy in milk, only to find in adulthood that it seriously exacerbated inflammation/autoimmune issues. I know for certain that casein is a large part of the picture (thank you industrialized food for isolating casein and scattering it all over). (before ceasing milk, I never had lactose issues) I'm intolerant of a pile of other things - gluten among them.

      When I was counseling parenting, I regularly ran into parents whose kids had all the hallmarks of a person intolerant of inflammatory foods (annoying how those differ from person to person!), and we'd work through a quick elimination approach. Remove gluten, casein, corn, soy, eggs, nuts & chocolate. (and needless to say, processed foods - additives and preservatives are a disaster in sensitive individuals) [insert re-introduction/information gathering formula here, long and boring and fairly obvious]

      It was astonishing how many children's "discipline problems" EVAPORATED when these foods were removed from their diets. Basically inflammatory foods functioned as drugs for these kids, screwing up their bodies & brains beyond their ability to compensate and remain socially/age appropriate.

      Interestingly, this group was heavily self selected to include breastfeeding - often extended nursing right on through the toddler years. The kids reacted to whatever mom ate - kicking off whatever cascade of sensitivities were going to appear over the long term. My kids both reacted to gluten and casein eaten *by me*, within days of birth.

      It's such a complex picture. Fascinating to see new pieces of the puzzle in the research all the time.

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    5. Navilus, I've never tried kefir but do react to Greek yogurt. So you might want to experiment.

      With regard to lactose intolerance, Gab/Gemma, now I know what you're talking about. The real crux of that article is in the discussion section, next to last sentence:

      "However, small bowel injury, such as celiac disease, inflammatory bowel disease (IBD) or gastroenteritis can lead to secondary lactose intolerance [50] with reduced lactase activity. Lactose intolerance will lead to an increased concentration of lactose in the colon, resulting in symptoms such as bloating, flatulence and diarrhea."

      I didn't know that "secondary lactose intolerance" can arise from bowel-driven autoimmunity, such as IBD and CD. This fits "sudden-onset" and prior lactose tolerance. Plus, bowel-driven autoimmunity could fit just about all autoimmune conditions, more or less, if you include intestinal permeability in the mix. So that secondary intolerance could plausibly explain the symptoms when unsuspecting people consume dairy.

      However, that might not be the case. The other argument has been gluten as the battering ram and the "first mover," the first domino so to speak, leading to dairy, egg whites, etc. as the next dominoes to fall. This is usually regarded as woo by mainstream medicine. Dairy proteins, in other words, are pseudo-glutens to which the immune system reacts. Plus, you can't discount Neu5gc, which is implicated in the worsening of symptoms specific to Hashimoto's, though not to RA and other autoimmune diseases. Just yet.

      And here's my counterargument. The reaction that you see in autoimmune people (excepting those with IBD & CD) are usually not similar to lactose intolerance. It's not bloating, flatulence and diarrhea but the (i) worsening of symptoms specific to the autoimmune conditions you have and (ii) vague but unwell symptoms like brain fog, dry eyes and mouth, fatigue, malaise, etc. That's why I call it "dairy sensitivity," not lactose intolerance. Symptomatically, I think they're distinguishable. But that is an important, if shattering, insight, that certain autoimmune conditions can spawn secondary, i.e., sudden-onset, lactose intolerance out of the blue. That could explain some of the phenomena for those suffering from Crohn's, UC, CD, etc. However, for the majority, I don't think that's the case. In other words, gluten as the heat-seeking missile or the Trojan horse still seems plausible to me.

      See how confusing and confounding this can be. This is why when you go to online forums, you have to dismiss about 75% of anecdotal evidence, since most people are simply being Pavlovian and cannot analyze their bodily reaction with sufficient analytic rigor. Nor can they ever track long-term reactions their body undergoes when it's largely asymptomatic, like a frog being boiled alive. Throw in gullibility and susceptibility to false associations, and you have a breeding ground for superstitions like "cross-reactivity", "fat adaptation" and "metabolic advantage." Some people throw in "food avoidance" and "gluten sensitivity" to the mix, but no. These are proven remedies for people suffering from autoimmune conditions.

      Span-Carvan

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    6. I read this today, from a young mother discussing her 3 year-old daughter. Can anyone spot the issues involved and see why our society is not getting any better?

      In cases like this, a kid allergic to 'everything', what should be done? Is avoiding every trigger the right move for a 3 year old? What is this Mom setting her daughter up for in life?

      "Got daughter's allergy test results back. She is allergic to eggs, milk, quite a few grasses and trees, and the worst of all... She's severely allergic to cats and dogs. *heartbroken*
      They also said she has an allergy/sensitivity to gluten/wheat but doesn't have to completely avoid it.
      Based on her results, they are referring her to an allergy specialist.

      It is upsetting especially because those dogs are her best friends! But they said it's in her best interest to rehome them :(( it really is a bummer but she has been pretty miserable for a couple years now so I'm happy to have finally figured out the culprits & hopefully she'll start feeling better soon!"

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    7. Oh that's so sad. Imagine a 3 yr old having been "pretty miserable for a couple years now". I wonder how they'll be able to explain the loss of her dogs to her. Poor little lamb.

      What ever happened to kids growing out of allergies? I'm starting to feel like this is a different planet than I one I raised my kids on.

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    8. *headdesk* If they remove all food allergens for a good long while (years, let gut integrity be reestablished) and build/rebuild her gut bugs, chances are all that hyper-reactivity toward the critters would fade away.

      I've actually done this personally - I used to have a cat asthma trigger. I now live with a long haired cat. The only difference? Gut bugs & removal of inflammatory foods.

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    9. @wildcucumber - All the hygiene behaviours + environmental toxins is my current working theory. If the immune system is never given what it needs to build itself (a regular experience of illnesses, exposure to daily germs etc.) and the environmental toxin load is many times what it was 50 years ago....it's a good formula for a really whacked out immune system.

      When you add the over use of abx, decimation of gut flora & increasingly heavily modified foods to that picture, it's amazing *more* people don't have food sensitivities. Sigh.

      (hi! so nice to see you :)

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    10. Tim, bottom line: don't feed trees to your toddler.

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    11. Okay, so let's get serious here: Spanish, it's not that dairy is wrong. It's the lactose that's wrong and it's not because a person develops lactose intolerance at any point due to anything. It's because some people with lactase persistence somehow have an epigenetic trigger due to immune system stimulation continuing post weaning because of lactose ingestion that some autoimmune disease can occur: to be precise MS.

      Since it's my hypothesis, Gemma can kill me privately. But it's somewhat surprising to me that no one has realized that the geographic distribution of MS is also the same for lactase persistence and fluid milk consumption. It's not vitamin D because then Inuit and Innu and Sami would have MS and they don't. They are also lactose intolerant (unless interbreeding has occured with those Europeans who are lactase persistent). There's more....

      And it's not an infectious agent because to date, despite much searching, none has been found.

      Lactase is on the 2nd chromosome and in a gene cluster that contains a lot of homeobox genes. These tend to 'sort together' during meiosis. So is there something in the homeobox complex that somehow works with the lactase gene to cause the epigenetic changes? It seems that something happens to future MS patients prior to age 15 is what predisposes them to getting MS in the third decade of life. What's the trigger? What predisposes to the trigger? Is it lactase persistence or a homeobox gene that sorts with the lactase gene on the 2nd chromosome?

      Is there a gene on some other chromosome that epigenetically creates the havoc due to lactase persistence and lactose consumption?

      It's definitely ability to consume lactose that identifies the majority of classic MS cases. Why am I the only person who has noticed this? Is it because lactose tolerance is so ubiquitous to the MS population that no one has questioned it?

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    12. I'm surprised they fed her grass and trees when she so clearly preferred cats and dogs. lol.

      That took me a couple minutes.

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    13. @ Terra - welcome back to the land of the living! I think you're right, of course. I'd say fixing the poor kid's diet is more to the point than removing the pets (and breaking the girl's heart). There's also a big psychological factor in things like asthma and allergic responses. Who knows how much stress that kid is under. Taking away pets and instituting a strict diet will appear to have short term gain and then all hell will break loose again. I'd bet money on it.

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    14. Gabi, so what's your theory on what the trigger is?

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    15. I wish I could figure that out. But definitely it is the ability to digest lactose post weaning. You see, this is the ironic thing: lactose? No problem. Ah, but yes, problem. Some sort of dysfunction occurs precisely because it is digestible and influences the immune system in the gut.

      http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053876

      Karolinska Institute isn't a research backwater.

      So if lactose in babies provides a stimulus for immune competency, what happens when lactose is applied post weaning? What does it do to the immune system when technically it is no longer required? There is no animal model for MS and no animal has lactase persistence either.

      So is lactase persistence a universal evolutionary advantage or are there situations where it is detrimental? Why is it that classic MS is present among populations that have lactase persistence?

      On a population level, the incidence of MS is not enormous. On a personal level it is a tragedy.

      I think the only way to prove the hypothesis is to have a few thousand kids be weaned and put on a lactose free diet for 20 years. Not dairy free, just lactose free. There is lactose free milk available these days.

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    16. You see, wildcukey, I've been accused of not being able to 'think inside the box'. Everyone is looking for something bad. Something overtly pathological. HLA antigens, screwed up CD8s, CD4s.....crazy mast cells, manic macrophages.... whatever. I'm saying those are downstream from something much more basic. Hypothesis that is being majorly floated these days: autoimmune disease begins in the gut. (Back when I was doing initial work on what became my hypothesis because I approached the question from an entirely different angle and it just clicked and clicked in another way like Lego blocks, there wasn't much hoopla about guts.)

      Gemma sent me that PLOS article and it was something I had not seen before because it's recent work. I started this 'follow the yellow brick road' thing a number of years ago and shelved it.

      Now in the past few weeks I've taken it off the shelf, flew it by Gemma, and she's been literally peppering me with all sorts of stuff. But this gem (ah, gemma) popped up and I think it's an important clue.

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    18. Gaby, no one's looking at it from that angle. MS is primarily known as Europeans' disease, unlike something like Lupus, where the occurrence is much higher among nonwhites. So people are looking at genes, HLA-XXX, and the environment. Also, it's not perceived as a gastrointestinal issue but neurodegenerative, so they probably consider LP to be rather irrelevant. I can't find a single citation on LP + MS. But there are many on LP + IBD, which should probably be your direction of inquiry, as countries like Canada and Finland have the highest incidences of IBD.

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070862/

      MS is most common among northern and central Europeans, so the obvious things to look at are Vit D and UV exposure. Already, northern Europeans have the highest dispersal of the genes (HLA-XXX) linked to MS, so you combine low Vit D / UVB plus genes to establish correlation. The relationship does not exist among non-Westerners, e.g., the Sami you cite who live near the North Pole. Why? They don't have HLA-XXX. Also, there are exceptions to the pattern in Scandinavia where people consume lots of Vit D through food (dairy, herring, cod liver oil), despite the higher latitude.

      So most people will see the overlap with LP as incidental. Having said that, LP probably induces more dairy consumption and given the genetic vulnerability, you could see how dairy can kickstart not only MS but IBD; it's already implicated in T1D once you have CD. All you have to establish is LP induces more dairy consumption than when you're NLP, then factor in lack of sunshine and low Vit D levels and regress vs. incidences of MS, IBD and other autoimmune issues that are prevalent in the northern latitudes.

      There is probably no moolah for research like that here. It could be a career limiting move if you find nothing. So the scrappy Europeans that are most affected by LP and MS/IBD are the ones that shall plumb such relationships, such as Karolinska. However, that is a different issue than people reacting to dairy after having been stricken with autoimmunity. Plus, unlike lactose intolerance, dairy sensitivity in that context is usually not gastrointestinal, unless you have IBD/CD. Span-Carvan

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    19. @Spanish

      You do not understand. All this vitamin D and sun exposure and HLA combined do not explain high incidence of MS in Sardinia.

      Here another paper what lactose does (in vitro).

      Lactose inhibits regulatory T-cell-mediated suppression of effector T-cell interferon-γ and IL-17 production (2014)

      Delete
    20. Gab, you made me read about Robertsonian translocation, I made you read about MCM6 and Mount Etna. We are even, LOL

      Delete
    21. Spanish, actually the real incidence of MS in India is unknown. There is a lot more of it than is officially reported because of social reasons. Families hide their sick daughters. The weird thing about the MS clinic I read about was the patients were predominantly male. This is an artifact.

      There are areas in India where variability of lactase persistence exists. I probably wrote this wrong.
      http://www.huffingtonpost.ca/priya-sankaran/multiple-sclerosis-india_b_3287660.html
      http://www.huffingtonpost.ca/priya-sankaran/multiple-sclerosis-india_b_3288198.html

      Delete
    22. Moishe Velasquez in 'Evidence of Absence' talks about the MS in Sardinia quite a bit. He attributes it to Mussolini having the swamps drained which got rid of Malaria. Whatever the relationship between the immune systems of the Sardinians and the malarial parasites was broken giving rise to the high concentration of MS seen there. Interesting book, BTW.

      SL

      Delete
    23. Interesting, because 'evidence of absence' can also be applied to lactase persisters. No evidence of lactose causing digestive upsets etc.

      Sardinia is interesting in that the northern portion of the island was settled by a different people than the eastern and southern. IN typical island fashion the different groups don't interbreed. The northern portion is believed to have been settled by people from the area of northeast Iberian peninsula and further east from there. This, if my memory serves me correctly because it's been a number of years since I read up on it, would have been at the end of the Roman Empire. They were descendents of Germanic tribes. Whoever sacked Rome, that sort of thing. The eastern portion of the island was settled in large part initially by people from the southern portion of the Italian peninsula and north African coast. So there is some genetic difference as well.

      I doubt malaria or lack there of has anything to do with anything. Lots of areas in Europe were malarial until after the second world war. DDT at work......

      Delete
    24. But don't at least some of those formerly malarial areas have other issues if not MS, for instance, Cycle Cell Anemia? Could this be a case of immune systems gone awry looking for something to contain, like the malaria but finding none, turn on the body?

      Delete
    25. Taiwan: until 40 years ago high malaria. Very low MS incidence. Very low prevalence of lactase persistence.

      Delete
    26. Gemma/SL, Taiwan would have low MS-prone HLA and the same with Sardinia That's what mainstream research says.

      "Table 5 shows the effects of adjustment for the frequencies of several HLA-DRB1 alleles on the gradients within Europe. The significant inverse gradient in the Italian region was completely reversed on adjustment,"

      Gabby, I'm wondering if India might also somehow gotten hold of the genes through Portuguese or European influence, you know the folks who probably drink lots of goat milk and retained LP? Or the HLA-DRB1_15. There's already been such a study.

      http://www.ncbi.nlm.nih.gov/pubmed/17412364

      You might want to look at inner Mongolia, which would either have low MS-prone or high MS-protective HLA plus LP. Try to connect that to the Indians with Portuguese surnames or those with European heritage with higher HLA. That would be like shooting fish in a barrel.

      The discrepancy is explained away using traditional assumptions, people. No one's going to take the swamp thing story seriously. Remember, there is also one in Scandinavia, which is explained away by higher consumption of foods with Vit D, such as cold water fish and dairy. So dairy in that case can be protective as well as malevolent. How are you going to measure that? You eat lots of dairy and your serum Vit D goes up to protect you; at the same time, it might kickstart the disease process for IBD and MS. But it's a complete wash for MS.

      I keep telling you, if you're serious about LP, you need to look at IBD rather than MS, which takes out the latitude-Vit D dimension. The first article cited by Gemma supports the IBD link with lactose. But other studies have been done since LP and IBD are both gastrointestinal issues.

      And that LP argument jibes with the "gluten/dairy as diseases agents" theory as well, which also jibes with the inhibition of T cell immune response. When you have Celiac Disease, the second disease that piggybacks is usually MS or T1D. Dairy consumption, though not LP, has been specifically implicated in the pathogenesis. Why do you think so? If you have CD, you have the most pernicious case of intestinal permeability, a disease in which the sole culprit is IP. It's a plain vanilla case unlike other complex autoimmune issues like MS and SLE. No wonder it makes you vulnerable to other autoimmune diseases. It could be the particular leak or the "simulacrum argument," that dairy proteins resemble gluten and the body reacts similarly. Or that lactose inhibits T cell functioning and ups CAMP expression. Do you really need to distinguish one from the other? Doesn't that show you shouldn't consume dairy when you have autoimmune issues or are genetically vulnerable to them?

      The sequence of events is you first get CD but isn't dx'ed years down the road. In the meantime, you often develop MS / T1D. Dairy has already been specifically connected to T1D. Google. Why is that? Dairy as quasi-gluten or LP and lactose inhibiting T functions? In that case, LP wouldn't so much matter since with CD in place, any dairy consumption, not higher consumption, could kickstart the disease process, if you believe that dairy is pathogenic. Your challenge might be linking LP with such diseases since you don't need MORE but ANY consumption of dairy to be stricken with MS, T1 and other issues. Span-Carvan

      Delete
    27. Spanish, the data on Mongolia is very sketchy. Althought I have not done major searches. Mostly they ferment the milk anyway. Some of these areas, like Uzbekistan, Kirgyzstan etc. are difficult to get any data on. But mostly they ferment dairy as well.

      Turkey has data and I'll be taking a closer look.

      India is interesting because you've also got a sizable Parsi population in the Mumbai area. So there's genetics from Persia which as of today is reporting high MS rates as well. I think probably more so because there's some 'hope' for the sufferers rather than because there are more of them. In general, cows are sacred and sources of dairy product, paneer being non-fermented, so containing lactose. There's a huge variation between what is used in the very south of the country (coconuts) and going north where yoghurt is very popular. Drinking fluid milk is usually in boiled tea.

      The thing with northern parts of Scandinavia, (Sami) MS rates are low, lactase persistence is low and it 'appears' on the surface of it, that lactose intolerance and not consuming any dairy products results in lower rates of breast and bowel cancers. Which is interesting in as much as there is a lymph channel from bowel to mammary gland (Tim knows what this is called. I forget.) It's sort of a sod's law I think with some kinds of mammary cancer if there's movement of 'microbiome' inhabitants from bowel to breast.

      One of my first 'let's see' areas was Finland. MS rates in Eastern Finland are very low. Meanwhile MS rates in western Finland are the same as Denmark and Sweden. Why? MIgration. Eastern Finland was populated by migration from the east and the coastal areas were populated by Swedes and Danes since it used to 'belong' to Sweden.

      I think we need to distinguish them. And it's not merely consumption of dairy. It's consumption and ability to digest the lactose in fluid milk. This is important because in many places people consume fermented dairy because they are lactose intolerant.

      I haven't delved too closely into T1D and lactose other than consumption of fluid milk results in high blood sugar problems.

      I have a feeling that drinking fluid lactose free milk might be even worse for a T1D.

      Lactose free is what the Chinese are drinking. (of course, what else?) Apparently there is an export of lactose free milk from the Scandinavian countries to China. (ah at least something is going in the 'other' direction. :) )

      Delete
    28. @Spanish

      You might have missed it, we talked this article some time ago here.

      Could Multiple Sclerosis Begin in the Gut? (2014)

      Delete
    29. I'm going to complicate the issue a bit.

      High LP in Hadza, for other reasons than milk drinking, but as far as I know, no MS?

      Genetic Origins of Lactase Persistence and the Spread of Pastoralism in Africa (2014)

      "For example, our data showed that 47% of the Hadza, a Tanzanian hunter-gatherer population with no history of dairy production and with no known LP-associated variants, were classified as having the LP trait on the basis of the LTT. It is known that LPH, in addition to having lactase activity, has a second enzymatic activity at a different position—phlorizin hydrolase, which uses phlorizin as a substrate.9,52 Phlorizin is a bitter natural product found in bark, roots, and the stems of pear, apple, cherry, and other fruit trees that belong to the Rosaceae family and is present worldwide, including Tanzania, the homeland of the Hadza.52–55 Phlorizin has also been used as traditional medicine to treat fever and infectious diseases, particularly malaria.55,56 Hence, it is possible that the LPH activity in the Hadza hunter-gatherers might have been selected for a broader and more complex role than simply digesting lactose. However, further investigation of this hypothesis is needed."

      Delete
    30. Gemma, the thing with this paper is did they only test the Hadza living their traditional way or random Hadza including those that live in 'town'? Not to say that the 'townies' are drinking milk, but just as in who was tested?
      The 'townies' are the ones with the gut parasites, ironically or maybe not ironically.

      The Lactase gene in east Africa is another variant. Different evolution.

      But it's interesting that a.) possibly the Hadza have a more interesting past than we know (?) and b.) can plant matter as described in this paper actually keep the gene active in the gut? c.) or is it possible that even a European lactase persistent person, genetically, who consumes zero lactose post weaning and then many years later drinks fluid milk, will that person have no problems digesting the lactose? Is it a 'if you don't use it you lose it' or 'it takes a bit of challenge to ramp up production' or what?

      Delete
    31. Gabby, in that article about CBC's female raio announcer getting MS, they describe a rogue Italian doctor, Paulo Zamboni. Zamboni believed that MS results from blocked neck veins. The poor Indian woman was convinced that a venoplasty could cure her. Some people have died from the process.

      That probably describes the focus on LP among MS researchers. MS is considered an electrical disease; IBD and LP are considered plumbing (i.e., gastrointestinal) issues. It's like calling Roto-Rooter when you need the household electrical circuits wired.

      That's why people can't think outside the box. As Gemma's article about MS shows, it all starts in the gut, whethere they're electrical, plumbing or joint issues. Span_Caravan

      Delete
    32. MS researchers are focused on LP?

      Zamboni got his idea from a German doctor who published his findings of iron deposition around blood vessels in brain lesions back in 1863. The Germans were considering back in those days that it may be a 'venous drainage issue'.

      I think MS researchers are all over place and confused about potential causes and effect. They are looking for pathogens they can't find, antibodies gone awry that are inconsistent, white blood cells gone mad....etc.

      Something I thought of last night just as an aside: type IV afferents. They are not myelinated. I've got to ask someone with MS who has numb feet and no proprioception if the sensation of burning is still alive and well. It's the slowest nerve impulse because evolutionarily, apparently, the sensation of burning was not important.

      Mind you one of the things that I've learned is that attacks are not the BIG problem. It's ongoing and continuous demyelination in the grey matter that goes on regardless.

      Piya has been hosting The Current on CBC radio all this week. She sounds good.

      Delete
    33. Too much iron. Low manganese. Didn't Spanish say it's electrical disease?

      Back to pubmed, LOL

      Delete
    34. Gemma, what's needed is a "gut rehab," not the rerouting of electrical wires, plumbing pipes or gas lines. Zamboni thinks it's a ventilation problem. No, you need a gut transplant. I don't even think a fecal transplant will quite do the job when you have permeability.

      Gab, that's really the question. Through food avoidance, you can allay your symptoms but are you really stopping the progression? There are no antibodies for diseases like MS and AS. So if you're asymptomatic, you'll conclude that you've been cured. For other diseases, however, the antibodies are not as high as before but still elevated. The attack will crawl to a half-halt but it's still in the background.

      But there is a way out. You can put a stop to autoimmune attack via LDN. It works in about 75% of people. Teri Wahls claims it didn't work for her but I wonder if that was really the case. You can't exactly tout "minding my mitochondria" and LDN at the same time. The only real champion of LDN in Paleo is Chris Kresser, who's seen how effective it really is. And pretty much costless. It's sad that people are not availing themselves to this option, which comes with only slight side effects and is affordable. I'd call it the magic bullet. Span-Carvan

      Delete
    35. Spanish, here: http://www.nature.com/news/archaeology-the-milk-revolution-1.13471
      Nicely written article.

      The map is a perfect overlap on areas where MS is high.

      Don't, just don't be telling me it's casein. There's tons of fermented dairy being consumed in areas where lactase peristenc does not exist.

      I'll reply later to what you've written about LDN. I gotta get some sleep.

      Delete
    36. Gab, maybe not casein but I have a hard time believing that lactose-free milk is being sold and drunk widely in Asia. They're usually sold in powder form and my understanding is Asians drink fortified milk that has lactose. And for those with Celiac Disease, it is positively casein that is implicated in their intolerance of, and inflammation resulting from, dairy.

      http://www.ncbi.nlm.nih.gov/pubmed/17302893
      http://www.ncbi.nlm.nih.gov/pubmed/19268534

      But the map does seem to dovetail with the MS map. Why not try to link LP alleles to HLA. HLA isn't one-way street: some are MS-prone and some actually protect you from MS. Plus, having MS probably keeps you from contracting some other significant illness. If you have RA, it's impossible to have gout and vice versa. It's the genes.

      However, think about some poor guy who ends up with CD, T1D and MS. The 3 are proximate diseases and life really becomes difficult when you have such conditions start piling on you. Span-Carvan

      Delete
    37. "what's needed is a "gut rehab," not the rerouting of electrical wires,"

      OK, but Wahls used electrical myostimulation. I agree she forgot gut rehab.

      @geeks only

      We found that in animal model of MS, syncytin-mediated inflammation and death of oligodendrocytes was strikingly prevented by ferulic acid. See here

      Ferulic acid is a potent antioxidant, and redox modulator (its derivates too). Its action might be synergized by butyrate. Ferulic acid is also HDAC inhibitor, so is butyrate.

      Does LDN work by influencing opioid receptor (HDAC inhibition?) and/or via antagonist effect on non-opioid receptors (TLR4)?

      Delete
    38. Linking LP to HLA is only of value in a place like the French West Indies. In other areas of high MS incidence, interbreeding is low. There's a possibility that in regards to HLA, the small cohort of MS patients in Martinique and Guadeloupe could be extremely valuable. The African origins of the people are from what is today Guinea. The HLA profiles of Guineans is documented. The HLA profiles of French West Indians is also documented. However, the actual individual HLAs of the MS cohort has not been done. There are signficant differences in a large enough percentage of the population from the Guinean african founders.

      The epidemiological data indicates that children who migrated to France with their parents before age 15 and then migrated back to the Islands had a higher incidence rate of MS than locals. But who takes their kids with them when they migrate from the WI? Most people migrate without their kids and remit money to grandma to take care of the kids. I can assume that it was higher socioeconomic demographic. The chance that these people were products of interbreeding is much higher as well.

      'having MS probably keeps you from contracting some other significant illness' LOL! MS isn't significant enough? But yes sure, +++ with other autoimmunes is horrifying. I think there's a small cohort on Sardinia who have both MS and T1D.

      Japanese are able to drink about 200 ml of liquid milk without consequence. The school lunch program provides this thanks to influence of American Aid back in the 1950s. Their MS manifestation is the typical Asian type although more recently, classic MS cases are cropping up.

      Delete
    39. Gab, Sardinia actually disproves the hygiene hypothesis of Moises Velasquez-Manoff. Had to google to get his name correct. Moises, not Moses, should use only one surname if he's published; both are difficult to spell. The rate is higher in rural, not urban, areas. It's the genes:

      "On this basis we believe that, beside hygiene-related factors, genetics could represent a more relevant determinant of Sardinian high susceptibility to MS."

      http://www.ncbi.nlm.nih.gov/pubmed/14567554

      Plus, yes the Sardinian phenomenon goes against the latitude but remember the past study, where the latitude gradient was wholly reversed upon adjusting for HLA alleles; we're dealing with a genetically susceptible population in Sardinia. Is there any doubt?

      http://www.ncbi.nlm.nih.gov/pubmed/11603620

      When MS researchers say "Sardinian focus," they're talking about the genes. Why do you think they're coming down with T1? Because of dairy? It's because the common genes make them susceptible.

      http://www.ncbi.nlm.nih.gov/pubmed/11988243

      However, I do get your point about unexplained increases in places where they shouldn't be genetically susceptible. Places like Isfahan, Iran, which is also not latitude-challenged. They used to eat fermented dairy there, yogurt, but it seems they're starting to drink milk by the jugful, especially low fat and skim milk since obesity is increasing even in Iran. Why is MS increasing in Ishafan? The Iranian researchers are pointing to Vitamin D deficiency, which is likely if the women are shrouded all the time. But weren't the women shrouded before?

      Here's a possible clue. Dairy consumption in Ishafan has already been linked to an increase in PCOS cases. We're talking about milk here, not yogurt. Lactose, not casein. And the authors understandably try to pin it to low-fat milk, which would raise IGF-1 higher than full-fat milk, which has more estrogen and lowers IGF-1. But you don't have to buy this. You could just link it to increased lactose consumption in non-LP populations. Iranians are mostly non-LP people, right?

      http://www.ncbi.nlm.nih.gov/pubmed/21459809

      Why not just say people are drinking milk in places where they previously ate yogurt. Lactose inhibits T cell functioning and ups CAMP expression. The exact same thing is probably happening in East Asia, Latin America, the Caribbean, etc., where people not known for having autoimmune diseases are suddenly getting them. Sunshine and Vitamin D aren't going to protect you if you start eating dairy. Lactose, primarily, even though casein too could be problematic.
      Span-Carvan

      Delete
    40. Gemma, who really cares how LDN works. I used to know the mechanism but now I can't remember. What counts is it works. It works even better if you cut out gluten, dairy and egg whites. In fact, I said it works for 75%. I'm gonna revise that figure and say it probably works in close to 90%. The 25% saying it doesn't work probably don't know they're doing. Taking LDN involves some measuring stick, getting a dropper, dissolving the tablet in about 200-250ml distilled water to get the liquid dose out of the 50mg regular Naltrexone. Probably 1 in 4 can't do the math involved in the alchemy properly and end up with too weak or too strong a dose. If it's too weak, you'll think it's ineffective. If it's too strong, the side effects are too strong so you'll give up too soon. So the success rate is probably higher for those who can follow instructions.

      Actually there is a portion, about 10%, for whom it doesn't work and that was confirmed when Naltrexone was used to treat alcoholism and it was determined to be due to genes. So the 10% who don't respond is probably right for the low-dose naltrexone, which is just diluting the 50mg into tiny, tiny doses, like 3-4 mg. Span-Carvan

      Delete
    41. " who really cares how LDN works."

      I care. If its action is, say, also/mainly via HDAC inhibition, why not to use other more natural sources, and not a drug.

      Just an example: Examples of dietary compounds identified as inhibiting HDAC activity. (2014)

      HT Barney, thanks!

      And LDN also works via inhibiting TLR4: in that case bad news for saturated fat which activates inflammatory pathways via TLR4.

      Delete
    42. @Gemma
      I totally agree with you about using natural sources. I took at the list you provided and many of those I use everyday but yet I still have some trouble with my RA. I add, subtract and the list goes on over many years. So, I also understand people wanting to use LDN (the lesser of the evils among medication) because they have tried the natural route and either can't find the correct proportion or it is just not working period. I looked into LDN but then decided to keep trying my way. Believe me there are times when I am tempted and one being now. But once again I am back again to tweaking!

      I found zingiber zerumbet to be interesting and am considering to try and grow it to make some shampoo. Have already started with the rosemary leaf rinse and love it!

      Delete
    43. Gemma, LDN doesn't deal with HDAC. It works by boosting endorphins which modulates the immune system. It attaches to opioid receptors and immune cells, then blocks endorphins from attaching to them. This tells your body to naturally increase endorphin production, which spurs the stem cells, macrophages, natural killer cells, T and B cells and other immune cells into extra gear. As for TLR4, are you on a SFA heavy diet?

      But most people who want to push their autoimmune issue into remission think if they're asymptomatic, they've done it. It isn't. If you want the antibody levels to subside and get rid of the attack from the background, and possibly make your issue not progressive and screech it to a halt, LDN is your thang. Food avoidance will not stop your AI from becoming progressive, unless it's fledgling AI. Having said that, it will only work if you want it to work because some placebo and dedication are at work here. If you're half-hearted, you aren't going to go through the trouble of dosing yourself gradually to acclimate yourself to LDN at the right time and to optimize the dose for continued use. So for those people who're shopping around for remedies, no, it's not your thang. Focus on your food avoidance. It should be the last recourse if your goal is only relief from symptoms. Span-Carvan

      Delete
    44. Having said that, it's fascinating I'm already taking so many natural HDAC inhibitors shown in that article. I take allicin (garlic), green tea, cinnamon, turmeric, parsley, red wine, onions, berries, and basil. Mushroom extracts and bitter melon are on my radar. Some others I take not mentioned are thyme, apple cider vinegar, rosemary, oregano, unsweetened cocoa, flaxseed meal, glucomannan, Larch Tree Arabinogalactan, apple pectin, hemp powder, inuli/FOS, acacia fiber, Baobab fruit powder, Amla berry powder, noni, etc. Some of them I've run out and will not replace but all of the herbs I regularly eat with my bean/lentil soup and the berries with my avocadoes and some of the fruit/berry powder and fibers.

      Span-Carvan

      Delete
    45. "LDN doesn't deal with HDAC"

      I think it might.

      First, here a latest review:

      The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain (2014)

      "Naltrexone, however, exerts its effects on humans via at least two distinct receptor mechanisms. In addition to the antagonist effect on mu-opioid and other opioid receptors, naltrexone simultaneously has an antagonist effect on non-opioid receptors (Toll-like receptor 4 or TLR4) that are found on macrophages such as microglia [17]. It is via the non-opioid antagonist path that LDN is thought to exert its anti-inflammatory effects.

      The majority of work to date has focused on naloxone/naltrexone’s action on microglia TLR4 (e.g., [28]). However, it should be mentioned that the data do not perfectly fit a TLR4 hypothesis [29], and other targets have been proposed, including astrocytes [30] and NADPH oxidase 2 [31]. Other sites of action, including the opioid growth factor receptor (OGFr) [32], are being discovered, raising even more potential mechanisms of action. Given the multiple and varied sites where naltrexone exhibits significant pharmacologic activity, it will be difficult to determine with certainty the paths that are critical for the clinically beneficial effects. This area of research is being vigorously pursued by multiple laboratories."

      And now to opioid receptor and chromatine (geeks only!)

      Up-Regulation of the μ-Opioid Receptor Gene Is Mediated through Chromatin Remodeling and Transcriptional Factors in Differentiated Neuronal Cells (2010)

      Delete
    46. Regarding TLR4 and excess saturated fat, from:

      "One of the first-line weapons the immune system deploys against infection are molecules called Toll-like receptors (TLR). While complex in its workings, when the immune system comes across a potential invader these receptors are designed to evaluate if it is bacterial, viral, or fungal. If the body finds evidence of any of these organisms, the immune system can begin its attack immediately while the adaptive immune system assesses what specific pathogen it is facing [46]. One of the TLR weapons, TLR4, is designed to sense bacteria. Unfortunately the part of the bacteria TLR4 binds, lipopolysaccharide (LPS), contains mostly saturated palmitic and steric fatty acids [47-51]. Meaning that TLR4 can generate inappropriate signaling when exposed to certain saturated fats if in too great of frequency, amount, or homogeneity rather than in a more biological balance and dosage. Any resultant, abnormal signaling may lead to a misguided attack upon saturated fat when it is perceived as a bacterial invader [9,47-54]. The resulting inflammation in the gut can lead to a break down of barriers, allowing harmful substance to leak from the gut into the blood stream and contribute to immune dysfunction that worsens infection control [52,54,55]. Consistent with these in vitro and animal models, studies in humans reveal down regulation of TLR4 and increased LPS translocation occurring within hours of a bolus of saturated fat [54,56], while polymorphisms reducing TLR4 functioning are relatively protective against dyslipidemia, coronary artery disease, and metabolic syndrome [57,58]."

      Delete
    47. @Spanish

      I see no stinging nettle on your list! Isn't it growing just everywhere?

      Scientific basis of botanical medicine as alternative remedies for rheumatoid arthritis. (2013)

      "Recently, botanical medicines have become popular as alternative remedies as they are believed to be efficacious, safe and have over a thousand years experience in treating patients. In this review, we will summarize recent evidence for pharmacological effects of herbs including Black cohosh, Angelica sinensis, Licorice, Tripterygium wilfordii, Centella asiatica, and Urtica dioica."

      Stinging nettle also mentioned here:

      Inhibitors of Microglial Neurotoxicity: Focus on Natural Products (2011)

      Delete
    48. and let's not forget bee venom!

      http://www.ncbi.nlm.nih.gov/pubmed/20558236

      I wonder if there is some magic also in the 'sting' of the nettle and not just it's tasty salad.

      Delete
    49. @navillus

      Having posted all this, I understand the clinical experience may be different and very individual. It is just interesting to explore, and may give you some inspiration. People in the past used to rely on natural medicine and common plants all around, there was no research paid by big pharma and pills packed in a bottle.

      Delete
    50. I haven't tried the venom nor stinging nette just yet. Right now, I'm just taking a small step from Aged Garlic Extracts to Rishi and Deer Rearend Mushroom Extracts. So I'm trying not to be too tin-foil-hattish just yet.

      But ever since I went heavy legumes, I basically transitioned out of bone broth and my SFA intake is very low. I still eat occasional steak, sardines and some egg yolks. But beans and lentils have completely replaced my diet composition. I go to an Indian market and buy masoor gota (red lentils), kala chana (black chick peas), black matpe (black lentils), then some black-eyed peas, green lentils. Twice a day, I make my soup with some rice and 2-3 different legume variety and I can't think of going back to SFA-rich bone broth anymore. It's just too greasy and I get sick thinking about it. I am full from the legumes in ways I never thought I would. Plus during the day, I munch on yuca/cassava that I boil, then freeze and thaw, green plantains, and yams. My fat intake is so low now and I probably eat more than 300g of carbs. Span-Carvan

      Delete
    51. @ Tim - LOL, we're not going to get into the stinging nettle salad debate are we?

      The traditional method for relief from arthritic and rheumatic pain is to brush or lightly whip the area with nettles. It works well, just most people are averse to the stings. The tea alleviates all sorts of joint pain and gout. I'll let Gemma tell you the science side if she likes.

      Delete
    52. Oh LOL some more!

      Spanish, surely you're not thinking bee stings or nettles are in the tinfoil hat league! If so, I'd best be making myself one, I've been eating nettles for days and getting stung like crazy (which I enjoy),but does one wear the tinfoil shiny side in or shiny side out?

      Delete
    53. @wildcucumber

      Nice try. I feel like poetry instead :-)

      "Double, double toil and trouble;
      Fire burn and caldron bubble.
      Fillet of a fenny snake,
      In the caldron boil and bake;
      Eye of newt and toe of frog,
      Wool of bat and tongue of dog,
      Adder's fork and blind-worm's sting,
      Lizard's leg and howlet's wing,
      For a charm of powerful trouble,
      Like a hell-broth boil and bubble."

      Delete
    54. @ Gemma - cackle!

      O well done! I commend your pains;
      And every one shall share i' the gains;
      And now about the cauldron sing,
      Live elves and fairies in a ring,
      Enchanting all that you put in.

      Delete
    55. Spanish- with your high intake of legumes, I'd keep an eye out on your purine and uric acid levels. High purine is bad for your kidneys and if you have gout. I was eating lentils and black chickpeas every day for more than 6 months and my uric acid levels went crazy so I had to step back. Legumes and beans are great RS foods but they have some negatives too. Just wanted to toss it out there.

      T-Nat

      Delete
    56. Spanish, a high percentage of Iranians are lactase persistent. I'm trying to keep up here and read it all..... my goodness. I don't keep up with what happening here and now there's a deluge.

      Agree with you about naltrexone. Amazing how it helps with Crohn's disease as well. Makes a person wonder how increasing endorphins can have such a profound effect on what to all intents and purposes is an autoimmune disease. Modifies function of vagus nerve too? That vagus nerve: awesome.

      You and I must have some very different metabolic/immunological responses to pulses. The Americas types give me intense joint pain for days later. I walk stairs to keep my knees in shape but after eating kidney beans, I almost can't walk down the stairs. Chickpeas and black eye peas are okay but there's limits. If I would be eating like you are, my knees would be keeping me awake at night.

      I do make broths. Put them in the fridge, remove the fat and make soup all week long. This week-end I've used pork ribs.... ginger, garlic, shitake mushrooms, blah blah and lots of blah....;) Beef ribs I think are better. But pork ribs have more meat on them.

      Delete
    57. T-Nat, that should be some concern for gout sufferers. For them legumes, spinach, and tomatoes can raise UA, especially when combined with animal purine sources. However, they themselves are not triggers, I believe. Perhaps vegans do get gout from those few vegetarian purine sources. I did see my UA jump near 6, which is rare for me. But in return, my BUN is now around 10 and my A1c is 4.6, the lowest I ever tested.

      Gab, I don't think LDN will do anything to the vagus nerve. But it's also very effective for CFS and FM, treatment of which often involves vagus nerve stimulation. I don't eat kidney beans, Gab. I limit them to the ones that I can tolerate. I haven't tested myself on kidney beans yet. I'm all for lentils, black-eyes peas, garbanzo/chickpea types. Once you make them, put them in plastic containers, freeze, thaw when ready to eat, refreeze if switching to another legume kind. There're millions of options. After eating so much legumes, starches and grains (mostly white and brown rice), I just can't eat much SFA. I don't I'll ever touch bone broth again. Just the grease makes me gag. I use my leftover palm oil and coconut oil to fry egg yolks but once they run out, I'll be done with the oils as well. I just don't see the need anymore. And biomarkers are just much better on a plant-strong diet. Yes, I suppose you can call that plant-strong Paleo. Span-Carvan.

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    58. Spanish, okay then, you don't eat the beans from the Americas.

      I have only 1 place in my entire body that has inflammation: T11 herniation area. Have used naltrexone with success for the neuropathic component of the pain. This thing is a longterm misery. Not really possible to never twist the back and inactivity makes it worse. So today, my neighbours and I climbed up and down the very steep ravine and collected garbage. Tomorrow will be interesting.....we've got 4 more Saturdays of work to get done. Then, longterm, it should be fine. Garbage is not getting blown down there anymore these days due to infrastructure changes.

      Delete
    59. Gab, if Iranians are indeed LP, then that could support your theory. I thought the increased milk consumption, as opposed to just yogurt consumption (Iranians' staple diet), may have been responsible. But if they're already LP, then they would have been consuming lactose in steady doses anyway.

      They're trying to link PCOS in Isfahan, Iran to milk, though the presumed culprit is not lactose but IGF-1, since PCOS involves ovulation-driven infertility and lower estrogen levels. If Isfahan is one of those pockets of non-LP areas, then that would make more sense. But if LP, that could still support the view that higher milk-consumption drives MS and other hormonal dysfunctions like PCOS. Though it isn't very clear whether the culprit is lactose, IGF-1 or something else in milk. --Span-Carvan

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    60. PCOS and dairy, specifically milk, consumption in Isfahan, Iran.

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085920/

      And it's not the genes that's responsible for the high rate of Relapsing Remitting MS in Isfahan, Iran.

      http://www.ncbi.nlm.nih.gov/pubmed/25891570

      One of those rare places where you can eliminate both HLA (genes) and latitude (Vit D, though people will argue). What are you left with? Milk consumption. LP. Perhaps gluten as Western dietary habits take hold. Hygiene, maybe. But you've eliminated the 2 strongest variables casually tied to MS in an area where the rate is out of this world. That would be a researcher's dream, as far as conducting research.

      Span-Carvan

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    61. Spanish, I think I'm correct. But as to the actual mechanism, the immune homeostasis study indicating that lactose in babies is good. Now these other studies indicating that a.) not vitamin D, b.) not HLA, c.) not infectious although Gemma will go for imbalance of gut flora most especially fungi although yes, they can't live on lactose but people consume more than just fluid milk so there's other substrates. So I don't know what impact a couple of glasses of fluid milk per day would have on gut microbiome in a person with lactase persistence.

      Okay, so in Japan, a country of non-lactase persisters, the consumption of 200 ml of fluid milk per day does not have adverse effect as in diarrhoea, gas, etc. or at least that's what I've read. The only way this can be consumed without gut going nuts is if bacteria in the small intestine are able to break down the lactose. And then the intestine will absorb the glucose (maybe the galactose.... ) Classic MS is showing up in Japan. Records from 1963 (milk was introduce via American Aid Program in the 1950s), the Asian type of MS was noted. But more recently, the other form has appeared. School lunch program in Japan includes a small serving of fluid milk. Am I repeating myself? It's hard to go back over all the comments....

      So we need to add PCOS to the list, I suppose. I don't know enough about it but that Iranian study you linked seems to indicate that it's fluid milk causing the increase and not just 'dairy'.

      To paraphrase: "It's the lactose, stupid."

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    62. Looks like I will have to buy some stinging nettle seeds as I am not aware of any growing in my neck of the woods. As I plant them I will be sure to wear my witch hat and paint a black mole on my chin!😉

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    63. Spanish, the Islamic Republic of Iran came into existence in 1979. Prior to, women were in western dress. 45 years of chadors. Probably low vitamin D levels exist. Yes to change of diet. Yes to HLA differences.
      http://www.ncbi.nlm.nih.gov/pubmed/21566791

      But even their 'controls' were insufficent. Need to have at least 75 nmol/l.

      Delete
    64. @ Navillus - I can hook you up there, I have lots. No charge. Click my name, go to my blog, check contacts, email me if you're interested.

      Delete
    65. Gab, those East Asian countries saw their dairy consumption, especially milk, explode starting sometime in the 1980s. That was part of their national health campaigns, where eating Western style foods, including meats and dairy, was encouraged. And the increasing dairy consumption was probably responsible for the increase in average height in countries like South Korea, Japan, China, Taiwan. Such people would be in their 40-50s now, perhaps too early to be reflected in the statistics. But those growing up after the 1980s would have been exposed to tremendous amounts of dairy and their immune system probably were not prepared for the onslaught.

      Yes, milk consumption initially increased, followed by ice cream, yogurt, cheese, etc. But compared to Western countries, their consumption level still isn't that high. Perhaps a glass of milk in the morning. These people don't eat 3-4 bowls of Captain Crunch like I did growing up or even in adulthood. Or snack on a whole bar of Cracker Barrel like I used to. Instead, they drink something like "Banana Milk," which is pretty much like sugar water with some lactose, a diluted version of Quik Strawberry Milk.

      The Asian type of MS was initially noted but now the pattern isn't all that different from Western countries.

      http://www.ncbi.nlm.nih.gov/pubmed/23407702

      But the rate is still very low. They're quoting around statistics like 3 per 100,000, which is a just a blip compared to Isfahan's 50 and Sardinia's 200. Italy as a whole is about 70. Parts of Europe that are latitude challenged are 130 per 100,000. The Scandinavian paradox is that they're ~100 when it should be 130+ given their latitude.

      http://www.ncbi.nlm.nih.gov/pubmed/20956788
      http://www.ncbi.nlm.nih.gov/pubmed/23251838

      The rate is so low that we are talking about a patient population of less than 5,000 in all of East Asia, excluding China. About 3,000 in Japan. Compare that to Europe where there would be close to a million patients.
      Span-Carvan

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    66. I was just thinking, in re: vitamin D levels of MS compared to controls: They take the vitamin D levels AFTER diagnosis. Disabled people who are heat sensitive don't spend all that much time outdoors.

      Over here now, neurologists are putting MS patients on minimum 4,000 IU vitamin D3 per day. Some higher. I've heard 5,000 IU. Same clinic, different neurologist.

      Sufficent is considered at 75 nmol/l. But European studies put it at anything over 50. Here they are only testing when osteoporosis is diagnosed. A bit late, eh?

      Netherlands is also lower in MS frequency than you'd expect.

      French farmers have higher incidence than city dwellers but that could be a matter of ethnicity. There's a high immigrant community in big cities. So much for the hygiene theory there too.

      The Scandinavian data needs to be broken up between the Sami and Lapps who live up north and the rest. The rates are very different. And the immigrant population in some urban parts of Sweden is 15% of the population. Middle east and Africa.

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    67. Gab, those Vit D charts in Iran are not in ng/ml. They're in nmol/l. So they define insufficiency as under 30 ng/ml and deficiency as under 1 ng/ml. You can clearly see the disparity between men and women. Men are not shrouded and properly work outdoors; women are indoors and shrouded. But you see how the difference between control and case isn't all that pronounced. Those with MS are definitely lower and perhaps significantly lower but Vit D levels are not determining in the onset or prevention of MS. 14% of MS patients is normal while 38% of control is. How did they get MS, assuming these levels reigned when the MS disease process kickstarted? It's always multifactorial. One among many factors. You are stricken with MS only when a whole chain of events line up. You have to be pretty unlucky to get MS, especially even in places like Isfahan. Span-Carvan

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    68. Gab, here's your answer. No need to chase our tail here; someone's already done the heavy lifting. Check out the discussion sections of this article:

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070862/

      Switch IBD for MS and they're parroting you. It's the coevolution of genes and LP that shapes predisposition to diseases like IBD, MS, etc. See the countries with the highest IBD incidence (Table 1): Finland, Iceland, Oz, NZ -- all high LP countries. LP (or NLP) as a variable is more robust than even latitude or UV ray.

      "LP status evolved in conjunction with pastoralism and herding (the gene-culture coevolution hypothesis) ... Emergence of LP status is hypothesized to have incurred an increased risk of intestinal infections and death as a result of drinking unpasteurized milk. A number of genes may have coevolved with LP. For example, HLA types, leading to immune signaling ... two dozen other immune-related diseases share genotypes with IBD, possibly linking a common epidemiology."

      And if you have to link it specifically to MS, then:

      http://www.gastrojournal.org/article/S0016-5085(11)00200-9/fulltext#sec8

      "MS and IBD are ... genetically associated with a region of chromosome ... that contains IL2RA (IL-2 receptor, α subunit). IL-2 controls T-cell proliferation; its effects have complex mechanisms of regulation, based on low- and high-affinity binding to its receptor ... multiple sclerosis and IBD are both associated with alterations in IL-23 signaling, although in multiple sclerosis (unlike IBD) genetic associations with IL-23 pathway genes have not been established."

      Bingo. LP means predisposed to autoimmunity. And when lactose consumption increases among NLP people, that also spells autoimmunity. Stay away from dairy. Span-Carvan

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    69. Hey, Spanish - Nice work! Funny that the original Loren Cordain Paleo Diet 'banned' milk, but for all the wrong reasons. When you say 'stay away from dairy' what are you thinking? ALL dairy products...cheese, butter, sour cream, etc... What about yogurt and kefir type fermented dairy?

      When I was a kid about 6 or 7, I got it in my head that milk was "gross" and refused to drink it. Have not had a glass of milk since I was a youngster, but I eat loads of cheese.

      Well, certainly there must be some benefits to all the milk consumption in the world...right? What would happen if the world suddenly stopped drinking milk?

      Thanks!
      Tim

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    70. Spanish, I like the way you think. After Gab emailed me a summary of her hypothesis, it was this very paper you linked now that raised my attention, when I started to look for some more information.

      The point is though, LP was strongly selected FOR during evolution. So I tend to think it is not dairy per se, it is the way we use it now (pasteurisation, etc.). Fermented dairy with low to no lactose is not the same, in my opinion.

      Delete
    71. Gemma, I tend to think that it's not pasteurization that is the problem in and of itself. It's pasteurization and refrigeration so lots and lots of fluid milk is available which is the problem. Quantity. Historically milk could sour up and maybe small quantities could be consumed 'fresh'. Now, huge quantities are available 'fresh'.

      Delete
    72. And along those lines, increased consumption leads to a need for increased production which leads to non-trivial changes in the animals producing the milk perhaps.

      Delete
    73. Tim, Cordain to his credit did say dairy, along with cereal grains, was responsible for Crohn's. He did read research linking IBD with dairy. But there was no need for him to tie it to LP.

      Gemma, that McGill study on IBD-LP is rich and complex, and considers all contradictions. For colon cancer, dairy consumption while being LNP may be somewhat protective because lactose acts as a prebiotic agent for bifidobacteria. What a surprise:

      "In another situation, LNP may be protective despite regular dairy food consumption via the effects of undigested lactose on microbial flora. In such cases, lactose could act as a prebiotic, promoting protective bacteria like bifidobacteria. This scenario may represent an ecological fallacy on comparison of outcomes in epidemiological and patient-based studies, as has been shown in the case of colorectal cancer."

      The same with unpasteurized (raw) milk, which was found to be somewhat protective for Crohn's among presumably LP Brits.

      http://www.ncbi.nlm.nih.gov/pubmed/17237136

      So there are some contradictions and you can quibble about pasteurization. But LP is a variable independent of latitude / Vit D and explicates the worldwide spread of autoimmunity rather well.

      "The findings ... support ... that the evolution of LP together with pre and post divide migrations contributed to the observed geographic spread of modern diseases currently common in western / industrialized societies. We propose that the relationship between latitudinal polarity (north-to-south, south-to-north) and LP/LNP distributions mimic each other’s disease-modifying effects through global LP–LNP polarity on a large scale ... the analysis shows that LP/LNP distributions can have independent effects from ultraviolet B exposure."
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070862/

      If you read the Cho study carefully, you'll see that I did a little snow job to link MS with IBD. Among autoimmune diseases, MS is actually not as close to IBD as AS, CD, psoriasis, T1D, etc. But it's close enough to suspect a common pathogenic pathway involving lactose consumption whether you're LP or NLP. See Tables 1 and 2.

      http://www.gastrojournal.org/article/S0016-5085(11)00200-9/fulltext#sec8
      Span-Carvan

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    74. @Spanish

      The first study you link does not mention unpasteurized (raw) milk at all. It says:

      "Multivariate analysis showed that consumption of pasteurized milk (per kg/month: odds ratio (OR) = 0.82, 95% confidence interval (CI): 0.69, 0.97) was associated with a reduced risk of Crohn's disease."

      Here another paper on Crohn's that does mention raw milk:

      The Association between Childhood Environmental Exposures and the Subsequent Development of Crohn's Disease in the Western Cape, South Africa.

      "Environmental factors during childhood are thought to play a role in the aetiolgy of Crohn's Disease (CD). However the association between age at time of exposure and the subsequent development of CD in South Africa is unknown.

      This study included 194 CD patients and 213 controls. On multiple logistic regression analysis, a number of childhood environmental exposures during the 3 age interval were significantly associated with the risk of developing CD. During the age interval 6–10 years, never having had consumed unpasteurized milk (OR = 5.84; 95% CI, 2.73–13.53) and never having a donkey, horse, sheep or cow on the property (OR = 2.48; 95% CI, 1.09–5.98) significantly increased the risk of developing future CD. During the age interval 11–18 years, an independent risk-association was identified for; never having consumed unpasteurized milk (OR = 2.60; 95% CI, 1.17–6.10) and second-hand cigarette smoke exposure (OR = 1.93; 95% CI, 1.13–3.35)."


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    75. That's correct, Gemma, that's the case of the McGilll article not describing the finding accurately, since it said "a British study suggested a possible protective effect of unpasteurized milk consumption in CD." It was pasteurized, not unpasteurized. That article was really about Mycobacterium avium paratuberculosis (MAP), which would be in water and dairy and was thought to cause Crohn's. MAP is not eliminated via pasteurization. If MAP causes Crohn's, then it wouldn't be negatively associated with IBD incidence. That was a study among LP people who consumed dairy, where dairy was negatively associated, which is one of the contraindications of the main thrust of the McGill paper.

      The second article you quote is really the hygiene hypothesis, especially regarding exposure to farm animals. That is Moise's mantra and it works well when you compare the relative paucity of IBD occurrence in the 3rd world vis-a-vis developed countries.

      "That infectious diseases are still rampant in areas inhabited by large LNP populations raise the question of their role in infections modifying host immunity. Immune reactions to such agents have been postulated to protect against modern day allergic and autoimmune diseases..."

      Or when you want to show how someone who migrated from an LNP area to a country like Canada would develop MP, as Piya did. The hygiene hypothesis is really based on migration studies. But intranational studies like the one you cite do not work as well. The SA study needs to be looked at along ethnic lines and also LP. Span-Carvan.

      Delete
    76. Spanish, how could anyone tell anything about IBDs in underdeveloped countries with the underdeveloped healthcare systems? Diarrhoea is so common it's 'normal' to get the shits frequently due to contamination of food or oral fecal/oral other body secretions/excretions. They haven't gotten with the program. To wit: ebola.

      Delete
    77. Gab, you didn't read that McGill article cover to cover, did you? It's all in there. That is an A+ first-rate paper. An A+ paper covers all grounds, including all previously-mentioned contradictions, yet still forges ahead with the main thrust of the research, reconciles all prior counter-evidence while remaining skeptical about the conclusion to be drawn. The inference drawn is restricted but reasonable, only limited by the strengths of the correlations and supporting evidence. The paper said,

      "Countries with higher LNP frequency populations tend to be economically disadvantaged. This is true largely in South America, Africa, and south Asia. Countries like the People’s Republic of China, South Korea, and Japan have already or are adopting more western lifestyles. Most of these countries had lower rates of IBD until towards the end of the last century. It is therefore possible that reporting of IBD rates is influenced by lack of experience with IBD or in economically less favored countries by lack of doctors and inexperience with the disease."

      So East Asia isn't necessarily impoverished and those countries have very high rates of colorectal cancer. Korea has the highest rate worldwide. And their rates of IBD are rising quickly and are not reflected by the study data, which goes back to 2000 or prior years since you also need accompanying LP/NLP data. There is no question that IBD is increasing rapidly in non-European OECD countries like Korea, Japan, Chile, Mexico, etc.

      "In an interesting study of the incidence of inflammatory bowel disease (IBD) among young males due for conscription in 2003 to 2008, the mean annual incidence of CD increased from 1.8 per 100,000 persons in 2003 to 2004, to 2.7 per 100,000 persons in 2005 to 2006, and to 5.1 per 100,000 persons in 2007 to 2008 [18]. This indicates that the incidence of CD is increasing rapidly in young Korean males."

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164717/

      5 is going up there with Western European countries like France. In the 1980-1990s, the rate was miniscule at 0.5 per 100,000. Why? Pushing milk to unsuspecting NLP populations. Milk made such people taller but they're falling prey to autoimmune issues like IBD.
      Span-Carvan

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    78. Yeah, I read about the high rate of colorectal cancer in Koreans. Well, so much for kimchi, eh?

      I don't know anything about fluid milk consumption in Korea. The Korean supermarket here sells dairy but there's minimal uptake. The section is quite vestigial. I think they stock for the whiteys like me who shop there. I buy at the Halal supermarket: much cheaper (and they carry the lactose free stuff that doesn't taste weird.) Yesyesyes I put it in my morning tea. I'm fearless.

      I think the younger generation of Koreans (and wow some of the women are quite statuesque) has more to do with more nutrition...period. The previous generation didn't exactly have good access to all nutrition in general. Korean War and all that.

      I was looking at stuff in Korea like raw sewage being dumped into the ocean. It's really terrible. They've made so much 'progress' but they aren't treating their sewage. The water near coastal cities is full of shit, literally.

      Delete
    79. Gab, the high rate is probably due to pork and drinking. East Asia is one of those places where they drink hard and eat lots of processed pork to be merry. Guess which countries are in top 20: Eastern and Western European countries and East Asia. All are top 25 in drinking and pork consumption. Remember how Paul Jaminet linked processed pork to HBV and stomach/intestinal cancer? There is this one commonality.

      Which countries have the lowest CRC rates? The Hindu-Muslim world. They won't be caught dead eating pork or drinking hard in places like Morocco or Iran. NLP and dairy may play a role but higher meat intake is very strongly correlated with cancer in East Asia. Sorry, Paleo, but you just can't ignore it.

      Span-Carvan

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    80. Spanish, the whole CRC thing is off my radar right now. My only understanding about CRC is low pH poop is associated with low CRC rates. Lots of resistant starch helps for prevention. Hindu-Muslim world in south Asia is high resistant starch diet = pulses. Don't know about Morocco.

      Average age at diagnosis is also relevent since generally in 'developed' countries it's not a disease of the young. And life expectancy in countries where rates are reported as low has serious issues with comprehensive reporting.

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    81. For CRC and most cancers, it's very misleading. Most studies associate high meat consumption with cancer. But it's not the sin of commission but omission. If you increase your meat intake, you crowd out RS and fiber. It may not be that there's something inherently bad in meats but what eating meat prevents you from eating. It's the opportunity cost of eating meat that's the issue: those who eat cold cuts and burgers aren't going to be eating much RS. They'll go for fries and desserts.

      Processed pork, however, is something different and it could instigate cancer and liver diseases per PHD. And drinking hard liquor represents more than just alcohol consumption but associated behaviors that are destructive, just like smoking; it means you're reckless, so you're likely not to exercise or drive safely. That's Epidemiology 101. There is more to these variables than what they represent. Most people don't understand this. It's supposed to be counter-intuitive.

      For most epidemiological studies, eating animal flesh crowds out your opportunity to eat legumes, starches in their natural state, greens, and fruits. That's the effect most people don't understand. You have to think of it like how HDL, which is the strongest variable that's inversely correlated with CVD, works. You get CVD not because your LDL-C or even LDL-P is high but because your HDL isn't high enough vis-a-vis your total cholesterol to scrub your arteries. It's not direct but the inverse of what you're doing that's controlling in health studies.
      Span-Carvan

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    82. @Spanish

      "Having said that, it's fascinating I'm already taking so many natural HDAC inhibitors shown in that article."

      Interesting, from Potential of epigenetic therapies in non-cancerous conditions (2014)

      "Grabiec et al. (2010) set out to investigate whether the administration of HDACis would counterproductively induce further inflammation in diseases such as asthma, chronic obstructive pulmonary disease, or RA. They used TSA and nicotinamide, both HDACis, to inhibit class I/II HDACs or class III sirtuin HDACs and found that they could block the production of IL-6 and TNF-a in macrophages from both RA patients and healthy controls. This finding supports the notion that HDACis can selectively and effectively suppress proinflammatory growth factors, chemokines and cytokines that fuel RA patient disease progression (Grabiec et al., 2010)."

      Delete
    83. ...and from Grabiec: Histone Deacetylase Inhibitors Suppress Inflammatory Activation of Rheumatoid Arthritis Patient Synovial Macrophages and Tissue (2010)

      "Importantly, the induction of macrophage apoptosis by HDACis was significantly enhanced in the presence of TNFR and TLR ligands, inflammatory stimuli readily found in RA synovial tissue. Similarly, HDACis induce apoptosis of RA stromal FLS only in the presence of TRAIL (34, 62). Selective effects of HDACis on cells in inflammatory tissue were also observed in vivo; topical application of TSA and PheBut induced cell cycle inhibitor expression in the tissue of arthritic, but not nonarthritic, rats (32). Thus, therapeutic administration of HDACis might selectively induce apoptosis at sites of inflammation in RA. Our results suggest that although HDAC activity may be reduced in RA synovial tissue (23), residual HDAC activity plays an essential role in maintaining cellular activation and survival and presents a potential opportunity for therapeutic application of HDACis in RA."

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  8. [waves wearily from the land of Lung Viruses] Nice to be back reading everyone's delightful thoughts! We had the lung thing that's going around - took out my whole household for weeeeks. Glad to be mostly done with that :)

    Interesting gut bug thing: for about 10 days there my only intake was potato starch. Though I ate no other food and was coughing hours per day, my energy and mental clarity remained very good. Yay for potato starch! Yay for well-nourished gut bugs!

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    1. Glad to have you back amongst the living! Hope you are done with all that sickness stuff for a while.

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    2. Good lord me too, Tim! TWO lung viruses already in 2015? *makes 'hex aversion' signs* But hey, we were WAY more robust in weathering them than other families I know. YAY GUT BUGS :D

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  9. I don't where I should ask this question but I am interested in thoughts in reference to what this doctor has to say about how low "Vitamin" D effects our gut bugs.

    http://drgominak.com/sleep/

    Gina

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  10. Spanish, if you research the scientific literature on Pubmed, you will find that there also is a lot of vit D deficiency going on in Saudi Arabia. Why? Because the women are covered with head to toe and so don't get any sun unless it is in the privacy of their own homes, where no stranger can see them. So it is not just confined to Northern countries.

    Jo tB

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    1. Jo, it's the Saudi men too. It's incredible how low the vitamin D levels are in Saudi. 4 or 5 ng/l. So long as the babies are bottle fed, at least they are getting their vitamins. Otherwise there would be an epidemic of rickets.

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    2. Art Ayers emailed me these thoughts the other day, adding the wrinkle of "inflammation" to why we can have low D levels despite lots of sun exposure:

      "Cats get all of their vitamin D by secreting precursors in the oils that coat their fur. Cats lie in the sun to promote UV production of vitamin D in their fur and then groom extensively to swallow their daily dose of D. This has implications for indoor cats, who will not get vitamin D fur production through glass.

      Skin pigmentation, angle of the sun and sun block are irrelevant to solar vitamin D production compared to chronic inflammation. Sun baskers in San Diego and Miami are still vitamin D deficient, because chronic inflammation blocks solar vitamin D conversion in the skin.

      Typical vitamin D3 supplements, e.g. 1000 IU/d, for measured vitamin D deficiency were found to be ineffective, because the supplements were insufficient to suppress the underlying chronic inflammation. Higher supplements, e.g. 16,000 IU briefly, that were sufficient to suppress chronic inflammation, permitted solar production of vitamin D in skin to resume, and serum D normalized.

      Even brief exposure of skin to sunlight generates more vitamin D than a supplement, but only in the absence of chronic inflammation.

      Symptoms of an inflammatory disease usually indicate chronic inflammation sufficient to suppress vitamin D production by skin exposed to sunlight.

      Serum vitamin D deficiency indicates chronic inflammation. Inflammatory disease symptoms make vitamin D deficiency likely.

      Sunburn is enhanced by suppression of vitamin D in skin/chronic inflammation."

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    3. Well I guess my time in the sun is kind of pointless then... I just got back from a massage and the therapist said I had a great deal of inflammation along my spine (not like I couldn't tell by how I was feeling!!). I will keep up the fermented cod liver oil and the Vit D3 supplements (my levels did finally show in the normal range last Oct. when I got them checked. First time after 7 years of supplementing and I credit that to the addition of the potato starch!).

      Gina

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    4. Art is super correct. A person with Crohn's disease can sit in the tropical sun for 'time' every day and still be low in Vitamin D.

      However, superhigh doses of Vitamin D can get remission in about 50% of Crohn's patients. Dr. Grimes..... GI specialist, Bradford, England.

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    5. Wow - fascinating on the inflammation/low D connection. I wonder how a low tolerance for oral D fits into this scenario. I have low D, I have high inflammation, and don't tolerate even moderate oral D intake..... clearly there's some piece of the puzzle missing. I'll be interested to see whether my improving gut resolves this apparent contradiction.

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    6. Terra - Are you intolerant to D3 and D2? My wife had super-low D, they put her on something like 30,000IU a day for 2 weeks, retested D, which was now good, and gave her no more instructions after that. She's been taking 5000IU/day of D3 since then and her D levels stay around 50-60.

      But, she is also a die-hard sun-avoider and was just found to have high levels of calcium which is indicative of parathyroid problem and/or low D levels. It's all intertwined. I wonder if taking Vitamin D supplements is actually just screwing people over by making them "think" they have their Vitamin D problems corrected...from http://endocrinediseases.org/parathyroid/parathyroid_calcium.shtml

      "Vitamin D helps the intestines absorb calcium. However, the vitamin D must first be activated or "turned on" by parathyroid hormone (PTH). Once activated, vitamin D acts to greatly increase the amount of calcium that the intestines can absorb from food, sometimes by as much as two to four times. The body can either make its own vitamin D using a process that requires sunlight or obtain vitamin D directly from the diet (e.g. in fortified milk or vitamins). Many people across the world have vitamin D deficiency — experts estimate that one-third of Americans are vitamin D deficient.

      For patients with vitamin D deficiency, it is difficult for the body to obtain calcium from the diet. This often leads to a rise in the PTH level, since the parathyroid glands must increase the PTH production in order to increase calcium levels by "stealing" it from the bones. Therefore, people with a normal blood calcium levels and a high PTH level may have secondary hyperparathyroidism(see Special Cases: Secondary Hyperparathyroidism), which means that the high PTH level is a normal response of healthy parathyroids glands to another problem (like vitamin D deficiency or kidney failure).

      It is quite common for a person to have both primary hyperparathyroidism and vitamin D deficiency, since primary hyperparathyroidism can lead to decreased vitamin D stores. This can sometimes make it difficult to establish the diagnosis of primary hyperparathyroidism. It is generally advisable to have the blood vitamin D levels checked during the work-up of parathyroid disease. For people who may have both primary hyperparathyroidism and vitamin D deficiency, some are best treated with surgery first, and others are best treated with vitamin D first. This decision should be made with your physician."

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    7. The calcium intake recommendations need to be modified to take into consideration optimal vitamin D levels (now we know what they are or should be). So in the past the recommendation was something like 1000 mg of Calcium per day. But if optimal vitamin D levels mean that absorption is improved considerably, then intake of calcium can definitely be fine tuned downwards. For otherwise healthy people. Not relevent for those with osteoporosis. They need mag/cal/vitD/vitA/vitK2. People are low in magnesiusm intake which means calcium is not utilized optimally either.

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    8. I believe a vitamin D emulsion is better absorbed than capsules.

      Nicole

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    9. Nicole, the most important thing is to take vitamin D with a meal that contains fat. It's a fat soluble vitamin and requires bile to emulsify it and ensure absorption. Taking vitamin D with a cup of coffee in the morning is pretty well useless.

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    11. Thanks for reminding me that I need fat when taking vitamin D.

      Nicole

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    12. And if you want to be really picky, the type of fat may matter

      "The fat composition of the diet may influence the 25OHD response to supplemental vitamin D(3). Diets rich in MUFA may improve and those rich in PUFA may reduce the effectiveness of vitamin D(3) supplements in healthy older adults. More studies are needed to confirm these findings."


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    13. LOL. I was wondering about the type of fat! Thanks for posting the link.

      Nicole

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  11. Gina, interesting item about vit D and gut bacteria. When I read up on vit D 7 years ago, our gut flora was not in the picture, nor vit B complex, so I never looked at the possible link. But reading that post, it sounds plausible, because vit D is necessary for a good functioning immune systeem and when that happens all systems are firing properly and that would include the gut flora. I think they are all inter-connected, so if one part is affected, the whole system is affected including our gut flora.

    Funilly enough my orthomoleculair dietician said I was low on vit B and so has prescribed a complex to be taken 3 times a day. As stated previously I have already been taking vit D for 7 years now, so I pretty much keep that up to speed. I will be taking more vit B along with my D in future.

    Jo tB

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    1. Last year we ran across several papers showing that when people eat an RS rich diet, they maintain higher levels of Vit D due to an interaction with gut microbes:

      http://www.ncbi.nlm.nih.gov/pubmed/25165393
      Rat study here, but seems there was also a human one showing the same thing.

      "Type 2 diabetes (T2D) is the leading cause of nephropathy in the United States. Renal complications of T2D include proteinuria and suboptimal serum 25-hydroxycholecalciferol (25D) concentrations. 25D is the major circulating form of vitamin D and renal reabsorption of the 25D-vitamin D-binding protein (DBP) complex via megalin-mediated endocytosis is believed to determine whether 25D can be activated to 1,25-dihydroxycholecalciferol (1,25D) or returned to circulation. We previously demonstrated that excessive urinary excretion of 25D-DBP and albuminuria occurred in rats with type 1 diabetes (T1D) and T2D. Moreover, feeding rats with T1D high-amylose maize partially resistant to digestion [resistant starch (RS)] prevented excretion of 25D-DBP without significantly affecting hyperglycemia."

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  12. hello....popping in been busy :) well cassien resembles YEAST.. bio hackers have made cheese from cassien and also turned it to yeast.. To me milk is a problem due to killed bacteria which should breakdown things(cassien . lactogoblin etc.... gluten wheat resembles yeast at the HWP1 protein... Alpha side.. SOY ... usually loaded with aspergillus mold . its a no wonder people start out diary /wheat then soy ---problems. most sinus problems stated in 1999 is related to fungus. There may be some good fungus and yeast but --your genes determine your ability to eat it... Most type O blood people tend to be low in bidifo certain strains(bifido) break milk sugars --some STARCHES.. most have lost bifido and LACTO strains due to poor eating and antibiotics , vaccines etc most with type O low in bifido also have more candida /fungus. Not a true believer in the blood type diet.. but if you look at the foods listed its actually kind of funny a diet( example type o) ---containing no yeast...no milk no wheat... see http://www.drlam.com/blood_type_diet/blood_o.asp I myself , had lower then normal bifido (in testing) ...i have several gluten genes , which can give me celiac or intolerance , I have all mutated defective FUT2/card15 genes (crohns) --- I got sick 3.5 years ago ended up with crohns...ulcer colits and -- became gluten intolerant , dairy and then starch.... 3.5 years later- I enjoy my beer , have an ice cream with the kid and on occasion eat some pizza or a burger with bread. Stool tests help-- and so do OAT tests and many other tests. Another key factor -- I say is lacto bacteria-- its main ROLE and purpose is the stomach.. many strains also block yeast or ferment with it.. why you see acid reflux and indigestion.. take a acid blocker --all your doing is removing the acid you need and allowing more pathogens to grow. VIT B's folic acid.... vit D is important -- for me it was from a soy, milk, wheat free source to get back to normal. Most look at stool testing. THERE IS NO ACCURATE way to look at lacto in exit stool testing. While it can live anywhere through the GI track...its main home is the stomach . I cant begin to tell and explain how out of whack my gut and GI track was--- high yeast..low bifido.. high bad bacteria.. many lacto strains helped.. if your a mess odd are milk yogurt and kefir arent going to help you as many pathogens or yeast will consume it first .. I see some benefit from mushrooms but to me it depends on blood type and genetics

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    1. @eddie

      "gluten wheat resembles yeast at the HWP1 protein"

      Thanks, it was finally confirmed:

      Humoral Immunity Links Candida albicans Infection and Celiac Disease (2015)

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  13. Edward, extroardinary. A recent stool test showed my Bifido was low. It was thought that it might be because my pH was on the high side, should be lower. I am a type O !!
    The test didn't show up candida (thank God) but did show high igG/igG4 levels for gluten and nuts. It is said that type O is the oldest blood group that the others are later adaptations.

    Jo tB

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  14. what test did you use for candida or yeast/fungus.... what stool test did you use to decide your bifido was low on the note of type O , in my gene testing Im also in the higher group of having higher Neanderthal percentage.. today Ive lost every clown doc ive seen-- yet i have no disease, if you look at the people in Sardinia -- most of my genes are italian from the east coast , and german . People in the east (italy) as well sardinia -- eat a died LOW to no yeast. they eat flat bread. risen bread is from lacto not yeast. they eat --specific beans... lots of veggies.. limted types of fruits. goat, lamb pig... there dairy and cheese is from goat or lamb-- cassien and lactobublin is different... they drink wine wine grenache

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  15. Speaking of mushrooms - would anyone care to hear about today's kitchen experiment?

    I'd seen somewhere that one could use powdered dried shitakes to boost the flavour of a sauce or gravy, so I whirred some up in my coffee grinder. Poof, talk about powdery! (Reminded me of the 70's, capping mescaline in Judy's mother's kitchen... but that's a story for another day)

    Anyhoo, I then put some in a cup and poured boiling water on, just to see how it behaved. Just as I expected, it clumped back up. I suppose if you were to heat the powder in whatever fat you were using to start your sauce with, it might not? (Chefs, please chime in!)

    But for those of you who dig the powders, it might work in a smoothie if you could disguise the earthy taste, and it sure would be cheaper/more convenient to make your own than buy it.

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    1. @wildcucumber
      It would be like making a roux. The consistency of the ground mushrooms is much like a flour, I suppose, and therefore the liquid needs to be added gradually so it doesn't clump.

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    2. @navillus - yes, that's what I thought as well. I'll be trying it soon. Dried mushrooms are so handy and full of goodness, the more ways I can use them, the better.

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  16. Just one more question, wildcucumber. Malabar spinach. I was given two small potted transplants by my dentist. He's like that. I have no experience and little knowledge about it. Heat resistant and prolific distant relative to more traditional spinach varieties. Soluble fiber. BUT! Is it invasive in Gulf Coast climates? I'm inclined to set them out somewhere and give it a go.

    Dental exam results? No cavities, improved perio numbers (gum health), and a relieved pocketbook. Homemade ferments, PHD'ish diet, and gardening get at least some credit, I think. And to celebrate I grabbed a pound of sunchokes and some dandelion tea at the store today.

    Fun!

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    1. @ Rudy - did you ask me another question before this? If so I don't see it ..

      I don't know malabar spinach. Had to check Wiki - looks yum! I can't help you with the invasive question, sorry. Good job at the dentist!

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    2. @wildcucumber. Yes. Re: your take on essential oils. I have friends who recommend them but like you I will pass. Thanks for both replies.

      Your blog is also a favorite. Again, thanks to you, among other things, I am hearing birds when in my garden so much more clearly...

      Dental checkups are much like routine medical checkups now. The docs look at results and say, "Everything looks good." They almost seem disappointed. Hard to blame them all things considered.

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    3. @Rudy - hey, that's all nice to hear. Let's put those medical professionals out of a job!

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    4. ................errrrr.........thanks Cukey.

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  17. Rudy, according to the web sites I get in Holland, you can grow the malabar spinach in pots, so suitable for small gardens and balconies. It is a climber, but none of the sites said it could be invasive. I suppose if you don't tie it up it will sprawl all over the garden, like with pumpkin. So I would train it along bean stalks.
    I would imagine, if you keep it in a large pot, growth will be restricted, but you will need to feed it a lot.

    Jo tB

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    1. @Jo tB. So it will be. One malabar plant in a large container at work as a demonstration on all things natural and another for the garden in the middle of a long row of newly sprouted okra. Okra trellis. Can't wait. Thank you!

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    2. The Malabar does climb, but did not branch out when we planted it along our deer fence last summer. Each plant was about eight feet tall.

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  18. @ Terra

    Here's some antidote for your speculations.

    During my third pregnancy, I couldn't get enough milk (I drank lactose free pasteurised milk). I drank ALOT.

    When my son was born, he had eczema. It was my husband who noticed that when I ate any form of dairy products, my son would get colic-y. So for as long as I nursed my son, I abstained from any form of milk products.

    I was hoping he would "out grow it" but he is 6 now and will still flare up with eczema (it's a two day delay) in the crock of his elbow and behind his knee with any dairy/milk products even with my homemade SCD style fermented milk.

    Nicole

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    1. Nicole, does this include goat milk?

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    2. No it doesn't.

      I never tried goats milk. It cost more than cow's milk plus I have to drive to a bigger town to get it. I just buy whole milk (3.25%) that is lactose free. For my son I buy coconut/almond milk with no soy.

      I became lactose intolerant somewhere in my twentys but didn't figure it out until 30 years old. My mom (deceased) and my sister are however not my dad.

      Nicole

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    3. Nicole, totally understand. But it does sound more like an allergy that he's got and protein in other than cow milk is different. That's all.

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    4. Thanks for the tips Gabriella. I was being to suspect casein intolerant or something like it.

      I am really not a fan of regular consumption of almond milk. I will look into goat milk at the supermarket.

      Nicole

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    5. Nicole, if you have a freezer, you can freeze milk and defrost it when you want. So if you find it but it's far from home, no harm, no foul. Just give it a good shake once it's thawed.

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    6. Thanks Gabriella.

      Nicole

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