Wednesday, 26 November 2014

Natto wearing off again (and Jun Scoby)

2014.11.27
I haven't eaten my neighbours homemade Natto in about 2 or 3 weeks (sorry, I should've made a note about the date), and I'm finding that some of the inflammation from Ankylosing Spondylitis is starting to creep back up on me. First my neck started to be a bit stiff from time to time. Now I'm starting to notice a bit of stiffness in my ribs too.

So then..Time to have some more Natto! First I will try some commercially made Natto and see how that goes. Then if that fails I will return to my neighbours homemade variety, which has been safely stored in my freezer for future emergencies. 

In the meantime I have been making Jun Scoby, which is very similar to Kombucha. A very yummy drink it is, but more than that, it also helps relieve inflammation and fatigue. These two go together you see.. Inflammation and fatigue. This Jun Scoby gives me so much energy! I sip it throughout the day and the effects last maybe an hour or two. And it is when it wears off that a little inflammation has been returning. 




UPDATE - 2014.12.01
Immediately after my initial post (Thu 27 Nov) I ate some commercial Natto that I had brought with me to work. The next morning I awoke and had no stiffness in my ribs or neck. So then yes, it seems that commercial Natto also works well at clearing my starch sensitivity!


UPDATE - 2015.08.26
I continue to be able to eat starch without Ankylosing Spondylitis inflammation returning. I don't need to keep eating Natto in order to maintain remission (despite what I may have thought when writing earlier posts). The change has been quite permanent.. except that mixtures of starch and fat are still an issue.

Monday, 24 November 2014

Simple Eczema Cure - Vitamin B3


In July I posted about how I had been using a homemade Vitamin B3 cream to clear my eczema. In the last two or three months I have switched to taking this internally instead. I found that if I take 500mg of B3 orally twice a day then this is sufficient to clear any eczema from my body. Taking it this way has been working very nicely for me. Much better to assist the body through nutrition than to whack the immune system into submission with an immune suppressant.

I'm finding taking it internally is a bit more reliable than using a cream. My body is still prone to various forms of inflammation (eg. rhinitis, proctitis, prostatitis) and I am gradually finding better ways of dealing with each problem. So with that in mind, I think it is sensible to treat this problem systemically, as there is a possibility that it will address some systemic issue.. and who knows, maybe it will knock out the root cause whatever that may be.


Abstracts, Quotes, Etc
I will repost some relevant quotes here..

This one shows that B3 can have an anti-inflammatory effect on the skin
Source: http://en.wikipedia.org/wiki/Nicotinamide
 Skin conditionsNicotinamide has demonstrated anti-inflammatory actions that may be of benefit to patients with inflammatory skin conditions.[4] These conditions include acne vulgaris, and the compound can suppress antigen-induced, lymphocytic transformation and inhibit 3',5'-cyclic-AMP phosphodiesterase. Nicotinamide has demonstrated the ability to block the inflammatory actions of iodides known to precipitate or exacerbate inflammatory acne.
 NicAzel and Nicomide are the names of oral acne medications that include nicotinamide as their most predominant ingredient, based on this area of research. Nicotinamide is also found as part of a new adjunct supplement combination called, AzerizinTM. According to the makers of Azerizin, this adjunct is part of their prescription dietary supplement product, which they claim helps manage inflammatory skin conditions. Nicotinamide is also used topically as a 4% or 5% gel or cream - as effective as topical 1% clindamycin (8-week double-blind trial) performed at the New York University College of Medicine.[5] Unlike topical Erythromycin or Clindamycin it does not precipitate bacterial resistance in treating inflammatory acne. Nicotinamide acne treatment is also available as Nicotinamide pads and cream. 
This shows that B3 can the effectiveness of neutrophil immune cells by up to 1000 times

Title: C/EBPe mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice
Source: http://www.jci.org/articles/view/62070?key=a39ce7efc2f764ede04
 The myeloid-specific transcription factor, CCAAT/enhancer-binding protein e (C/EBPe) is a critical mediator of myelopoiesis. Mutation of this gene is responsible for neutrophil-specific granule deficiency in humans, a condition that confers susceptibility to Staphylococcus aureus infection. We found that C/EBPe-deficient mice are severely affected by infection with S. aureus, and C/EBPe deficiency in neutrophils contributes to the infectious phenotype. Conversely, exposure to the epigenetic modulator nicotinamide (vitamin B3) increased expression of C/EBPe in WT myeloid cells. Further, nicotinamide increased the activity of C/EBPe and select downstream antimicrobial targets, particularly in neutrophils. In a systemic murine infection model as well as in murine and human peripheral blood, nicotinamide enhanced killing of S. aureus by up to 1,000 fold but had no effect when administered to either C/EBPe-deficient mice or mice depleted of neutrophils. Nicotinamide was efficacious in both prophylactic and therapeutic settings. Our findings suggest that C/EBPe is an important target to boost killing of bacteria by the innate immune system. 

[I have made an almost identical post to earthclinic.com here]

Sunday, 16 November 2014

Remission & Natto (NSD Book Chapter)

The following is a draft of content which I intend to be added to my NSD Chapter

-- Combatting fungi --

Polygodial 

In 2013 and 2014 I have been quite focused on combatting fungal infections. I tried out a product called Kolorex and in January of 2014 noticed that it helped with the dehydration that I had been experiencing at night. I looked up its active component Polygodial, found that it was an antifungal, and is found in Dorrigo Pepper, Australian Mountain Pepper, Horopito, Canelo, Paracress and Water-pepper. The Maori's of New Zealand traditionally used Horopito to treat fungal infections. Some interesting properties in this compound - it inhibits the ability of pathogens to form attachments to, for instance, your gut wall, bladder etc. 

By chance I found some Australian Mountain Pepper (also containing Polygodial) whilst browsing an Oxfam shop in Sydney. It cost about $10, which I considered pretty cheap as far as experiments are concerned. Worth a shot. I took a little Mountain Pepper and found that when taken on an empty tummy it very quickly cleared my nose (sinus/rhinitis), and Proctitis (itchy bum) cleared quickly too, as did the constant fatigue of my condition. Those three only took about 30 minutes to clear up. I found this remedy worked well if taken on an empty tummy with a glass of juice or water. When taken at dinner I would wake feeling refreshed and well rested - a state that I had become completely unaccustomed to. For so many years I have been waking up feeling tired, lethargic and as sleepy as when I went to bed. 

Another useful property was that Mountain Pepper would clear the dreaded "brain fog" that was so disabling, particularly at work. There was a downside however, it sometimes caused a bit of a headache, but only for a short while (possible die off reaction). 

Is it possible that so many of those little gremlins that are eating away at my quality of life .. that so many of these symptoms are caused by a fungal infection? Sinusitis, proctitis, brain fog, and fatigue, these all cleared after consuming a known anti-fungal, ie. Polygodial from Australian Mountain Pepper. 

After a few weeks of usage of Mountain pepper it seemed to take larger doses to achieve the same result, and after a month or so it just stopped working. Typical.. I have experienced this several times before with other things (Ginko tea, and Bromelain for instance). I expect it will only work again after a long pause in its usage.

Lufenuron

I had read about an interesting compound called Lufenuron a while back - most likely in 2013. In February of 2014 I plucked up the nerve to finally give it a try. The first two days nothing happened of note as it needs to build up in your system until the right concentration is reached. I was taking about a half teaspoon daily and it had to be taken with fatty foods. Typically I used yoghurt or almond butter.. or both all at once. 

On the third day was when things started to happen. My head was very clear, that was nice. However the jock itch I was experience became -worse-. Not only that, but the Proctitis was noticeably worse, there was a burning sensation when peeing, and there was some abdominal pain in the vicinity of the prostate. All very interesting but it didn't phase me at all and I pressed on. This was almost certainly a fungal die off reaction. 

On the fourth day things improved. My head was still very clear and I noted that I could think and make decisions better than previously. The jock itch had calmed down and now there was some skin peeling where it had previously been a bit inflamed. Proctitis was completely cleared, as were the abdominal pains, and prostate. It did burn a bit when urinating still. That afternoon I drank a bit of alcohol and unfortunately that undid much of the good work! Back came some mild proctitis, mild prostatitis, brain fog and also the night dehydration. I think the alcohol only temporarily worsened these issues. About a week later after finishing the course of Lufenuron I made a note that the old problems all seemed to gradually return. So typical. These little gremlins sure are tough to shift. 

Fiji 

In very early May 2014 I was taking Lufenuron again but stopped before going on my holiday to Fiji. I felt it was better if I didn't have to try and explain the product as someone may find a white powder strange or suspicious in some way. Instead I would take my Australian Mountain Pepper with me since it was apparently nothing more than a condiment. Of course it is much more than that to me. 

I was taking my mountain pepper quite regularly during my holiday. The extra energy was most welcome as we went travelling and snorkelling on gorgeous little islands. One island was so small you could walk across it in thirty seconds. The snorkelling was wonderful, the coral were both beautiful and fascinating, and those vibrantly coloured fish!. 

In mid May my fiancé and I were exploring Nadi town and became hungry. We sat down at an Indian restaurant - not a good choice for someone on a No Starch Diet. I ordered something but apparently chose quite poorly.. well, poorly according to my dietary needs. But my senses were telling me otherwise and I did succumb to these. The curry was delicious and couldn't resist!

Here are the notes which I made at the time:

"Ate quite a starchy indian curry yesterday whilst eating out. My partner told me it definitely had besan flour in it to thicken it up, and it reacted immediately to iodine. Decided to try it anyway, "for science!" Hehe. It was just tooo yummy to turn down.
About an hour or two later I started to get very very tired which is a classic symptom for me when eating starch .. But the painful inflammation never came! Looks like the anti fungal compounds I have been taking are keeping this disease at bay!?!"

Natto

This year I had moved into a new flat in Sydney. My neighbours from unit 7 were very kind, they greeted me and asked if we could meet for a chat to which I agreed. Whilst we chatted in my flat they noticed my interest in supplements and quite sensibly realised I had some health problems. When they asked, I mentioned that my condition was very much linked to the health of my digestive system. They were both quite keenly into health, but from a uniquely Korean, or Asian, perspective. They recommended things a westerner might never consider: homemade Natto and Kimchi. 

One day my neighbours made some homemade Natto for me. I tried it on Tuesday night (10 June 2014) and soon posted a photo on my blog. At first I was not noticing much in terms of immediate changes. A few days later I believe my jock itch became a bit more inflamed and then calm down again, this much was similar with what I observed taking Lufenuron. It was that weekend when things became interesting. My fiancé had booked us into a winery tour of Canberra and the surrounding region. There are some really nice ones in the area if you know where to go. For lunch we stopped at the Four Winds Winery. They focus on their wines really, and for food it is just pizza and more pizza. I brought my own food as I had been forewarned of this situation. But wow the pizza looked sooo good! I told my fiancé it would be worthwhile trying starch again and seeing how well I tolerated it. Usual excuse. Lets face it, I have a weakness for good food. My fiancé was a bit wary but I said I would just have a little and see how I went. I suppose that when the only thing you have on the menu is pizza, then it ought to be bloody good pizza.. and they did not disappoint. The pizza was as amazing as it looked and smelled. And did I stop at one slice? Oh noo .. I couldn't stop. So yummy!

When we were back on the bus a few hours after lunch I mentioned I my fiancé that I should have been feeling some symptoms by now.. But I wasn't. For over 10 years I have reacted to starch like clockwork, but not this time. Why didn't I react?. I believe I hadn't yet put two and two together and made the connection with Natto. It may seem obvious with hindsight but my first suspects would have been Lufenuron and Polygodial.

Normally my reaction after a starchy meal shows up within less than 4 hours and then peaks at 24 hours, then gradually subsides over another two days. Three days of pain all up. The only exception is that on very very rare occasions after months of very carefully following a no starch diet I can sometimes get away with some starchy food.. but just once though as after that my immune system is primed again and a full blown reaction will occur. 

I kept taking the Natto for several weeks and noticed that it made my eczema worse, so I decided to stop taking it for a while and let my eczema calm down. It took about a week but the starch sensitivity returned (on 10th July 2014) and AS came with full force after eating some cheap hummus. It wasn't even good hummus. I would put up with some pain for good quality hummus but this it was not. Anyway, I decided to try the Natto again and lo and behold the AS calmed down within 24 hours of consuming Natto. Not bad eh. So that was it then, the Natto was surely the thing which had brought me into remission this time, although it didn't explain my experience in Fiji. Why didn't I go into full blown inflammation, as I should have, when eating that starchy curry in Fiji? Was it the Lufenuron or the Mountain Pepper, or perhaps both?
Bacillus Subtilis is a very very closely related strain to Bacillus Natto which is found in commercial Natto. It just so happens that Bacillus Subtilis is a popular alternative remedy for fungal problems. This is the one common thread I can see, both in my observations in Fiji and now with Natto - in both cases we see an anti-fungal at the heart of my remission. 
I asked my neighbour how she makes her Natto .. and she doesn't add any starter culture. So it is quite possible that wild Bacillus Subtilis strains have entered their Natto culture. Wild Bacillus Subtilis is found in soil and is an extremophile, which means it tolerates very extreme conditions. You can boil this one and its spores can still survive! The B. Subtilis culture could even be originating from the soy beans themselves.



Returning home to starchville

Now that I could eat starch again I went thoroughly overboard. Several kind hearted souls mention their concern for my sudden eagerness to jump in the deep-end of starch consumption. It was certainly testament to my lack of will power, but I wanted to try everything. All these starchy foods such as croissants, Vietnamese pork rolls, potato wedges, porridge .. All these many foods had been forbidden me for over ten years. Can you imagine not bring able to eat chocolate for ten years?

Observations about resuming starch

After a while I calmed down as I gradually started to take note of which starches were best for me. For instance deep fried starch as found in batter or doughnuts and the like can still cause me mild AS symptoms. This inflammation however is far far milder than the usual reaction, less than a tenth of the usual starch reaction. What's more the reaction is not only quite mild, but also short lived and always dissipates by the next morning. On several occasions certain foods (for instance cheese) caused my starch sensitivity to briefly return. Initially I had thought that I needed to keep eating Natto in order to keep my A.S. in remission, but it gradually became clear that this was not the case, and that the remission would always return. 

I tried eating normal rice, and even basmati rice, but both very reliably bring on quite severe proctitis, just as with glutinous rice. All those years ago when I first started cutting out grains I had kept rice until last. Well now I know why I had so much difficulty with proctitis and yeast infections at that time. How strange it is now to find that wheat, my mortal nemesis, is now my kind friend and rice now shunned. How the tables have turned. 

Sugar, in the form of sucrose, still poses a real threat to me. When I eat foods that are adulterated with refined sugar I experience pain in the region of my prostate & bladder. I also can experience proctitis and a strange dehydration that seems exactly like Sjögren's syndrome and which inexplicably worsens greatly when I sleep, followed by fatigue and weakness. 

I'm unsure at the moment but I fear the same problems as found in sucrose may also be found with very high glycemic loads such as with white bread? I reacted badly to a Vietnamese pork bun, however it is quite inconclusive since the sauces they use certainly do contain refined sucrose. I have some doubts though, since pasta and wholemeal bread are quite safe thus far. Well, I certainly do find that the same wheat starch can digest quite differently depending on how it is prepared - deep fried versus steamed, al dente versus over cooked, or fluffy white bread versus a denser wholemeal or rye bread. 

Whilst following the NSD a cavity in a molar on the lower right side of my jaw had healed to some extent. It lay dormant as long as I stayed away from dried fruits and excess of sweets such as chocolate. But upon eating starch (including amylopectin starch) I found that this cavity would become a problem again, and I must now be far more vigilant about dental hygiene. Weston Price would have much to say on this, I have no doubt (if he were still alive). 

My eczema has also returned once I resumed eating starch. It isn't too severe though, and I find that apple cider vinegar helps (both oral and topical) and 500mg of vitamin B3 also brings relief (taken orally, and this too can be used topically if you wish). But I have dwelled far too much on the negative aspects of starch thus far. Time for some positive words..

Eating starch again has made life so much easier, I now have far more energy and not nearly as prone to debilitating bouts of fatigue. My body temperature is very noticeably warmer, something I believe my fiancé may have first noticed when holding my hand. Normally I was significantly colder than her, whereas now I am noticeably warmer and tolerate cold weather much better. 

I had difficulty getting the energy I needed whilst following the NSD. Unfortunately my body never adapted well to burning fat as fuel. In fact fats from fatty food I ate would regularly be seen floating as an oil slick after going to the toilet. This inability to assimilate and make use of fat as fuel makes me a rather poor poster child for the NSD and it is not my desire to dissuade others from following it, but rather to be realistic about its benefits and shortcomings. An inability to assimilate fat doesn't seem to be common, and yet I'm certainly not the only person as I can think of one other who complained of this issue. He found that he needed some starch to help digest, or "bind" the fats in our food. Coconut oil is an exception here, as even my body finds this an acceptable fuel at most times. 

Now that energy levels had normalised I was also starting to gain weight, a situation I was quite happy with as I was a tad too skinny before. After putting on about 5 kilos my weight stabilised nicely. 

There seemed to be noticeably less muscular tension. For the most part I attribute this to eating less animal fat. A heresy for those following a Paleo-diet of course that I should say so, but too much animal fat was a problem for me. To each their own. 

I don't regret following the NSD, as it was what my body needed at that time. Without the NSD my disorder will have continued its course of degeneration and calcification of my major joints. And let's not forget the years of great physical pain that I have been spared. For this I have much to thank those at the kickas.org forum, and perhaps a little thanks should go to the indomitable spirit and the kindness of strangers. 

“There is in this world no such force as the force of a man determined to rise. The human soul cannot be chained” - W.E.B. DuBois

Friday, 14 November 2014

Probiotics. Good and Bad.


Us folk with autoimmune disorder almost always have some kind of dysbiosis - an imbalance in the flora of our gut. For instance, just as an example of the gut-immune connection, gut disorders like Crohn's disease and Ulcerative Colitis are both associated with Ankylosing Spondylitis. Also, taking antibiotics can bring autoimmune symptoms into remission briefly.. although the flora adapt quite quickly, especially the pathogenic ones. 

We are certainly missing key flora necessary for good health (called commensal flora). People have been brought into remission for months at a time via Faecal Matter Transplants (FMT). And I myself experienced an amazing remission of my Ankylosing Spondylitis after my neighbours gave me their homemade Natto. 

But that doesn't mean Yoghurt will help you much. It is beneficial in that it crowds out pathogens and corrects pH (acid producing flora are beneficial). Unfortunately beyond this, the standard probiotics don't do much. They just don't correct the underlying gut disorder, leaky gut or missing commensal flora. 

Some of us have experimented with more exotic probiotics - those with 10 or more strains. I can't get these in Australia so I have to order them online. 

There are a few things to be wary of with probiotics

Our experience as a group (on kickas.org) with probiotics are hit and miss. Worthwhile experimenting with though..But be warned!.. Two members have actually had there AS become worse after taking probiotics. One had a stiff neck for the duration, and the other had his AS badly worsened for some weeks afterwards. Both these people were seasoned followers of the No Starch Diet, and knew to check for starch. 

Starchy additives are quite a common issue we face, as are other polysaccharides used as probiotics, namely inulin and FOS. So watch out for these. 

The other possibility is that the immune system is cross reacting with the flora (think "reactive arthritis" or "molecular mimicry"), especially when the gut lining integrity is poor (leaky gut). When flora get past the gut wall and into our blood stream out immune system will become highly irritated. 

More likely the new flora stimulated their immune system, thus causing the existing immune disorder to worsen. 
This immune stimulation with the flora is what I believe may have happened to the two seasoned NSD followers mentioned earlier. It is fairly rare for this to happen, but I just want people to be aware of this possibility.




----------------------------------

- gut disease and yeast
Antibodies against S. cerevisiae are found in 60–70% of patients with Crohn's disease and 10–15% of patients with ulcerative colitis (and 8% of healthy controls).[2]

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Anti-Saccharomyces cerevisiae antibodies (ASCAs) have been proposed as serological markers, which may differentiate Crohn's disease (CD) from ulcerative colitis (UC) and predict disease phenotype. Their importance in pathogenesis is unproven. We investigated the relationship between ASCAs, disease phenotype and NOD2/CARD15 genotype in CD and whether ASCAs were related to antibodies to other fungal proteins. Serum from 228 patients [143 CD, 75 UC, 10 with indeterminate colitis (IC)] and 78 healthy controls (HC) were assayed for ASCA. Antibodies (IgA, IgG) to other fungal proteins (Fusarium species ATC20334, Mycoprotein) were measured in the same samples using an in-house enzyme-linked immunosorbent assay (ELISA) assay. ASCAs were present in 57% of CD, 19% of UC, 30% of IC and 8% of HCs. ASCA-positive status was a predictor for CD with sensitivity of 57%, specificity of 87%, positive predictive value of 78% and negative predictive value of 68%. ASCA was associated with proximal (gastroduodenal and small bowel involvement) rather than purely colonic disease (P < 0·001) and with a more severe disease phenotype and requirement for surgery over a median follow-up time of 9 years (P < 0·0001). No associations with NOD2/CARD15 mutations were seen. There was no association between ASCA and antibodies to MP (IgA or IgG). These data implicate ASCA as a specific marker of disease location and progression in CD, emphasizing the heterogeneity within IBD.

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Sunday, 2 November 2014

Dairy - study shows potential health risks

I am interested in this study given that many people who suffer from ankylosing spondylitis found that unfermented milk contributed significantly to inflammation.

Summary of points raised by this research:

  • Milk (non-fermented) worsens oxidative stress and inflammation
  • Fermented milk (sour milk and yoghurt) reduces oxidative stress and inflammation
  • Drinking unfermented milk did not reduce the risk of fractures - in fact the reverse was observed!
  • D-Galactose is highlighted as a possible explanation for the health differences between fermented milk and non-fermented milk. Unfermented milk is a major dietary source of D-Galactose. Galactose has been shown in animals to accelerate ageing and worsen oxidative stress.
My personal opinion is that there are differences in how fermented/unfermented milk digests in the gut / feeds harmful/beneficial flora, and that this is more likely the cause, especially given the changes observed in the immune system.



Milk intake and risk of mortality and fractures in women and men: cohort studies
BMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g6015 (Published 28 October 2014)

Abstract
Objective:
To examine whether high milk consumption is associated with mortality and fractures in women and men.
Design:
Cohort studies.
Setting: Three counties in central Sweden.
Participants: Two large Swedish cohorts, one with 61,433 women (39-74 years at baseline 1987-90) and one with 45,339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997.
Main outcome measure:
Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture.
Results:
During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker).

[following are some quotes from the body of the full text article]

Conclusions:
High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.
[...]

Biomarkers
D-galactose supplementation in animals has been shown to increase oxidative stress and inflammation.4 5 6 7 To assess the association between milk intake and biological markers of oxidative stress and inflammation
[...]
Milk intake, oxidative stress, and inflammation

We further investigated whether milk intake was associated with oxidative stress and inflammation. Milk intake was positively associated with 8-iso-PGF2α in both sexes, and with interleukin 6 in men (fig 4⇓). Consumption of fermented milk products (soured milk and yogurt) indicated a negative relation with both the oxidative stress and the inflammatory markers (see supplementary figure C, panel A). No such association was observed with cheese intake (see supplementary figure C, panel B). Milk intake and risk of mortality and fractures in women and men: cohort studies

Results
[...] In women, higher rates were observed for death from all causes (adjusted hazard ratio 1.15, 95% confidence interval 1.13 to 1.17, for each glass of milk), cardiovascular disease (1.15, 1.12 to 1.19, for each glass of milk), and cancer (1.07, 1.02 to 1.11, for each glass of milk) (table 2 and fig 3⇓). Milk consumption corresponding to three or more glasses of milk a day (mean 680 g a day) compared with less than one glass a day (mean 60 g a day), was associated with a hazard ratio of total mortality of 1.93 (1.80 to 2.06) in women, with approximately similar estimates for cardiovascular mortality and somewhat lower for cancer mortality (1.44, 1.23 to 1.69). For women who consumed three or more glasses of milk a day the hazard ratio for any fracture was 1.16 (1.08 to 1.25) and for hip fracture was 1.60 (1.39 to 1.84).

[...]

Comparing milk with other dairy products
Particularly noteworthy is that intake of fermented milk products such as yogurt and soured milk and cheese were associated with lower rates of fracture and mortality. Furthermore, we observed a positive association only between milk intake and markers of oxidative stress (urine 8-iso-PGF2α) and inflammation (serum interleukin 6). Previously, we found a negative relation between bone mineral density and 8-iso-PGF2α.42 63 Interleukin 6 seems to be causally related to cardiovascular disease64 and may influence bone loss and osteoporosis.65 Importantly, those who consume high amounts of non-fermented milk have a more non-favourable cardiovascular risk factor profile, with higher blood pressure, lower high density lipoprotein cholesterol levels, and higher insulin resistance.18 In contrast, intake of cheese and fermented milk products is related to higher high density lipoprotein cholesterol levels, less insulin resistance, and a lower risk of myocardial infarction.18 22 23 24 In addition, a recent small randomised cross over study indicated that the intake of a fermented dairy diet seemed to provide a more favourable biomarker profile than that of a non-fermented dairy diet.66

Potential mechanism
One potential candidate for the discrepant results for different types of dairy products is D-galactose content. The intake of D-galactose from non-fermented milk is considerably higher than that from other food sources, including cheese and fermented milk products. Non-dairy sources of D-galactose are mainly cereals, vegetables, and fruits,67 but the concentration of galactose and the amount ingested from these sources accounts for a small proportion of the total intake of galactose. Put into perspective, the amount of lactose in one glass of milk corresponds to approximately 5 g of galactose, whereas the amount in 100 g of fruits or vegetables67 is measured in milligrams or tens of milligrams. D-galactose given to laboratory animals (mice, rats, and drosophila flies) is an established experimental model for premature aging, including shortened life span caused by oxidative stress and chronic inflammation,4 5 6 7 but whether this mechanism can be generalised to humans needs further scientific support. However, galactosaemia is a genetic disorder that results from loss of galactose-1P-uridylyltransferase, with accumulation of galactose in blood and other tissues as a consequence.68 69 Affected infants experience a rapid escalation of potentially lethal acute symptoms after exposure to milk, and experimental models display oxidative stress as a mechanism for the development of disease.68 Even with dietary restrictions of galactose intake these patients have higher circulating levels of galactose and an increased risk for chronic diseases in adulthood,69 including osteoporosis.70

Conclusion
A higher consumption of milk in women and men is not accompanied by a lower risk of fracture and instead may be associated with a higher rate of death. Consequently, there may be a link between the lactose and galactose content of milk and risk as suggested in our hypothesis, although causality needs be tested using experimental study designs. Our results may question the validity of recommendations to consume high amounts of milk to prevent fragility fractures.3 71 72 The results should, however, be interpreted cautiously given the observational design of our study. The findings merit independent replication before they can be used for dietary recommendations.