Friday, August 06, 2010

Urate, ascorbate, resveratrol and land mines

It only needs a brief glance through the literature to realise that uric acid is a prime mover in metabolic syndrome and might reasonably compete with cholesterol as the premier mammalian-synthesised molecule of self destruction.

Until of course you come across interesting papers like this one which suggests that uric acid is a signal of tissue injury, a mobiliser of repair systems and, in particular, a recruiter of endothelial progenitor cells.

In modern terms, stepping on a land-mine will produce a surge of uric acid to blunt the effects of the renal ischaemia which will occur as you bleed out through the remains of where your foot used to be. In evolutionary terms you can see how surviving acute trauma might be beneficial and it looks like uric acid is seriously useful in this context. Stepping on a land mine every day fairly rapidly becomes problematic in terms of all cause mortality and even uric acid is unlikely to maintain its efficacy with prolonged usage. Chronic drug induced hyper uricaemia appears to be a Bad Thing in that it blunts the benefits of acute elevations.

If you don't live in a heavily land-mined country you are (a) lucky and (b) more likely to be injured by a bottle of cola or a bowl of apples. Or maybe oranges, stawberries, kiwis etc. Whether it is simply the fructose in the cola or some other plant nasty in the fruit in addition to fructose isn't particularly clear. But your body produces a spike of uric acid in response. It's been injured.

It is perfectly possible to consume cola or fruit on a chronic basis without the immediately obvious effects of repeatedly treading on a land mine.

This leads me to whether there are direct benefits from minor damage of eating fruit via hormesis or whether it is just all bad. I suspect it depends on the dose and the chronicity. When you look at WHEL and PPT there may well be some sort of accommodation which leaves total mortality unchanged by eight years of eating extra fruit and veg. There seems to be little doubt that an acute rise in uric acid is beneficial and chronically elevated uric acid may be less so. This flies in the face of Kwasniewski's opinions about uric acid, the more the better. But he is talking about elevated uric acid in a LC high saturated fat situation, not after eating a bowl of apples a day for a few years.... Of course he never cites references but I'm keeping an eye out!

Ascorbate is interesting as it is a rather ubiquitous antioxidant and does appear to be used by humans for assorted essential functions, all be it in very small amounts, despite the fact we cannot synthesise it. Most mammals tightly regulate their ascorbate production to their needs as they can produce it on demand. Not so humans. We don't produce it and our intake is completely random, varying from 10mg per day or less on an all meat diet to a few 1000mgs if you fall face down in a clump of cranberries and keep eating all day.

The chances of you meeting the cranberries every day for six weeks are slim, so if you want to study the effect of relatively high doses of ascorbate on free radical mediated processes in humans you have to use supplements. Eating 1000mg represents an awful lot of berries but is a common supplement dose.

This group in Spain actually pre empted the group in Germany in demonstrating the adverse effects of ascorbate supplementation on the effects of exercise.

Exercise produces free radicals, free radicals signal for both muscle cell division and mitochondrial number increase (using the surrogate of cytochrome C for mitochondrial number).

If you dose with 1000mg ascorbate daily you will scavenge the free radicals and blunt the increase in both muscle mass and mitochondrial number which should have been generated by those free radicals. You might expect this and it's worth noting that the effect appears to clearly detectable but far from complete.

I have worked on the assumption that taking antioxidants should down regulate your own endogenous antioxidant production. The Spanish group used rats for this part of their research and did indeed find that gene expression for synthesis of both superoxide dismutase and glutathione peroxidase are markedly down regulated. A zero increase with ascorbate supplemented exercise compared to a 3.5 fold increase after three weeks of unsupplemented exercise.

Think of the implications. You exercise, exercise generates free radicals, free radicals build muscle and upregulate production of antioxidant enzymes. So exercise is, fundamentally, antioxidant (while ever it is kept within the limits which can be accommodated by synthesis of SOD and GPx). Obviously ultra-marathon runners must be willing to injure themselves for their sport.

Mega dosing with ascorbate markedly blunts the induction of the intrinsic antioxidant system of mammals, even of a rat which naturally produces ascorbate.

What about resveratrol? Feed it to a mouse in quantities equivalent to between 150 and 1,500 bottles of wine a day and you get some improvement in inflammatory markers. Do you simultaneously down regulate SOD and GPx synthesis? Now there is a question!

That will be a cracking study. The answer will be yes if resveratrol really scavenges significant numbers free radicals. Our own endogenous antioxidant systems are fine tuned to our needs. What does a blanket treatment with a highly potent antioxidant do to our ability to respond to the daily alterations in free radicals? Free radicals carry information. How do we replace the information lost if they are stuck to a resveratrol molecule?

Luckily our bodies try hard not to absorb the stuff and normally metabolise it to sulphated or glucuronated forms within minutes. It's unlikely that we ever have much free resveratrol (or dark chocolate favanoids either, phew) in our bloodstream until human ingenuity invented the resveratrol chewing gum.

Unintended consequences anyone?


BTW The Wiki article on resveratrol appears to be very contentious. Wiki becomes a battleground once you get on to sticky subjects like cholesterol and, apparently, resveratrol. I've kept the text for when it gets edited to "Resveratrol explains the French paradox and will make us live for ever"


  1. Hello, Peter,
    To extrapolate freely over time, the difference, then, between a present day Orangutan looking at a full moon and Man landing on the Moon, may be, among other changes, Man's loss of Vitamin C production through was it lost, I wonder?


  2. In fact it is very easy to megadose on vitamin C if you eat wild fruits. Rosehips have about 2500mg/100g and the Australian Kakadu Plum has over 3000mg/100g. Modern fruits have just (unintentially) had the vitamin C and antioxidants bred out.

  3. another one for the hall of fame, peter.
    what about the antioxidants in dark choco? would you say they have the same impact?

  4. One also need to remember that a cupful of rose hip or apple pip will cyanose you terminally.

    (to not mention plum stone ad libitum)

  5. Hi Leon,
    rosehips were used as source of vitamin C during WW2 as oranges were unavailable in Britain. There is no evidence that rosehips are toxic even in large quanties.

  6. Hi BigWhiskey, it seems to have been lost on several occasions and at least one evolutionary paper, which I've lost on my hard drive, suggests it's a fairly neutral mutation. Neither fruit bats nor Guinea Pigs have made it to the moon yet........

    Ah, blogblog, to be devil's advocate, have we bred out the vitamin C because that's the sort of fruit that caused us least problems????? Sweet fruit to spike uric acid as opposed to sharp fruit to spike ascorbate? But I do accept that rose hips are common in the UK throughout Autumn and well in to Winter (in the present environment). I doubt they would be ignored by hunter gatherers any more than the wild strawberries would have been. But 1000mg/day is a common supplement size and it doesn't seem to do us much good on an exercise basis.

    Leon, I had a quick look in pubmed re apple pips, they don't seem to feature in case reports of plant poisonings (of which there are plenty)....

    Gabriel, I think ascorbate may be uniquely problematic. Our cells have surface pumps specifically designed to pump out xenobiotics like resveratrol. Because I rather like chocolate (and it's a portable source of stearic acid) I like to think that the flavanoids are kept out of anywhere they can do too much damage. Ascorbate gets access deep in to the cell. We need it. How much is optimal????


  7. I take heed of the warnings of overdosing vitamin C, but I have noticed significant and obvious benefits to taking a conservative supplement of 500mg + small extract rosehips every other day.

    For one, I bruise less easily. Prior to augmenting vitamin C I often had bruises even though I always take a multivitamin with 100% dv for vitamin c. The bruising only went away when I took the higher dose supplement.

    My gums and overall dental health is better, myg ums no longer bleed at all and are quite healthy.

    The biggest reason I keep on with the C is because I noticed my energy was remarkably higher when taking it. I didn't expect this to happen so it wasn't placebo... rather, I looked at what the "energetic days" had in common and soon realized they were days where I took my C pill. Later I learned vitamin C converts thyroid hormone into the active form, T3, which would explain this well.

    I think it is a good idea to avoid megadoses of vitamin C, but I think most of us in the low carb world are actually hurting ourselves by not supplementing... at least speaking personally I have noticed clear benefits from taking C.

  8. As an active ODer, I have been pondering about uric acid levels.

    This as Dr Kwasniewski claims that high uric acid levels are associated with a higher intelligence and at the same time claiming that OD gives higher uric acid levels.

    A rather new study, discussing uric acid pros and cons

    This paper seems to support the intelligence association, but also finds an association to obesity

    This paper finds a correlation between uric acid and catecholamines - does OD give more of those?

    gambling increases catecholamines?

  9. Thanks Peter. I love vitamin c. I observed great improvements with mood/energy/bruising, gingivitis and allergy (natural antihistamines). I think it´s as always a difference wheter on SAD, keto, paleo or even fruitarians. Also your own metabolic state and health condition interferes. Quality is as with all supplements very important. I only take the buffered magnesium ascorbate. Resveratrol on the other hand is imho highly overrated. Alcohol per se is a great stress reliefer and all longevity studies shows constant alcohol intake of different origins. Btw France is on top with the highest liver cirrhosis rate. And the always mentioned island of Okinawa are not only big pork lover but also have their own brewerie! Orion beer. Slainte.

  10. This comment has been removed by the author.

  11. Hi Peter,

    Your point about the hormetic effects of fruit hark back to a question I posed on an earlier post of yours: Basically, can we reap benefits by eating large amounts of fruit very infrequently? This would raise uric acid levels without chronically raising insulin, blood glucose, etc. and you get the bodily response on a cellular level much like exercise.

    Could we actually use fruits/fructose to produce beneficial long-lasting responses resembling exercise??? What is your take on the practical application?

  12. Many years ago (BI - before internet) I came across a piece about folk poisons. Among other things it said there was enough cyanide in a cup of apple pips to poison one - of course, it has to crushed up and fed to the intended poisonee . . . . ! Further research revealed that this was a characteristic of the rosaceae, being particularly true of the prunus single-stoned variety. I was intrigued as I never liked liqueurs coming from the plum family and was pleased to identify the characteristic I disliked as the (very diluted) cyanotic smell. I ASSUMED that the apple pip information applied to rose hip as well and never since checked this fact. Thanks, BlogBlog.

    At that time, I additionally related the fact that I had never liked the smell of gorse flowers, to the realisation that to me gorse flowers SMELL like plum brandy TASTES. Most others describe gorse flowers as smelling like coconut. I have not been able to track the aromatics of gorse and see if there is any evidence to support the conclusion of my personal lizard brain.

  13. Does anyone have any thoughts about alpha lipoic acid? My understanding was that its beneficial antioxidant qualities come about not by gross supplementation of antioxidant substances, but by somehow facilitating natural antioxidant pathways somehow, especially glutathione.

  14. ...weird about the French and cirrhosis. That's what should be known as the French paradox--is alcohol actually the reason?

  15. I think fruit would have actually been hyperabundant prior to agriculture. This is because there would have been a huge amount of dispersal of seeds in the feces of the wild animals such as pigs, deer, horses and humans. (We forget there was vastly more wildlife in the paleolithic). For example there millions of wild apple trees in Kazakhstan. These forests are believed to have co-evolved with brown bears (Ursus arctos).

  16. @Susan

    Mike Eades is a fan of alpha lipoic acid? You might check his blog for information.

  17. Hi Its,

    I remember Dr Bernstein suggesting a maximum of 500mg of ascorbate daily for diabetics. While I was devouring his book first time round I was still very pro ascorbate and wondered why he limited it, his suggestion pre dated the exercise studies. He didn't really have a particularly solid explanation as I recall. But it looks like he was correct. But then the increase in cytochrome C was almost significant in the exercise rats with ascorbate and the CyC was expressed per unit actin, ie there would have been some increase in muscle mass and mitochondria, just no extra mitocchondria per unit muscle mass, is how I see it. Lower doses of C might have benefit without cost and somewhere between 100 and 500mg/d might well have more pluses than minuses. We do need some of the stuff. Just guessing...

    Hi Varg,

    Thanks for the links, I've just started to look through them, back in to running out of time mode again!

    Hi Byron and John,

    I think I have observational stuff that alcohol is neutral on all cause mortality, but of course that is of no interest to a cardiologist. Anything other than a heart attack is an SEP (Somebody Else's Problem, ref Douglas Adams again).

    Gunther, well yes. Activating the mobilisation of EPCs could potentially fix all sorts of problems so would parallel the DNA repair triggered by radiation exposure. But I don't see a lot of experimental data out there..... Practically I'm tempted to stick with what works. In the same way I'd like to see a replication of the cobalt sixty episode in Korea before trying to get hold of a used nuclear fuel rod to run my central heating system!


  18. Hi Susan,

    We excrete ALA as rapidly as possible, I think the dose is three times a day? I'm aware it is reputed to be very helpful for diabetic neuropathic pain from Dr Bernstein's forum but I do wonder about its long term effects. I guess it's a balance between unquantified worries and the severity of your diabetic neuropathy.


    As you know I am rather temperocentric and don't see a huge amount of fruit in the few remaining patches of climax woodland in the UK. I remember a commenter on either the OD forum or Dr B's forum that a similar lack applied to the Amazonian rain forest. There's fruit there, but not on every other tree.


  19. Leon,

    This is still not putting me off of Sloe Gin.... Ah, it's almost September!


  20. Peter, it's interesting to note that glucose actually LOWERS uric acid, and quite considerably depending on your level of metabolic syndrome.

    Does this mean glucose is healing us in some way, in the same way that uric acid levels rise when fructose is hurting us?

    Could carbohydrates' bad effects actually just be a question of which kind we eat, and how often? Since glucose and fructose are metabolised so differently and seemingly provoke conflicting bodily responses, could it be just the combining of the two that is problematic?

    Fruit contains varying levels of both, as well as sucrose, but I don't know what kind of fruit was around during the Paleolithic, but I will wager that it was mostly fructose and much lower levels of sucrose than we have produced today.

    It's notable that HGs, due to seasonal reasons and lack of refrigeration, can only eat high fructose (in fruit) separately from when they find starches (roots, tubers, etc., yes some have a bit of fructose too).

  21. Hey Petro,
    Enjoy your Sloe Gin, and I trust when you're sippin' yr first run, you have put on Clancy Bros " The Juice of the Barley for me".
    (BTW Did you note that Liam passed away last year?)
    Then on to Jamie Imlach wi' "floo'er o' the Gorbals" an' a' that!

  22. gunther, that's interesting. The people in the study seem to have high fasting insulin, and the fact that they have high trigs and insulin resitance implies (I think) some metabolic damage. I'm not sure how to interpret the results in this case. For people on a ketogenic diet, uric acid levels decrease with time (weeks) in addition to decreasing with small amounts of carbs (5%)...if you can get the full text...

  23. Most of the readers here are from cold Northern climates and assume that their vegetation applies elesewhere.

    I live in subtropical Australia where some 2500 wild native native plants were eaten by aborigines. Native fruits such as lilly-pillies, native figs, and blue quandongs are extremely common - thousands of these trees grow wild in my suburb alone. A local HG could eat their fill of fruit for 6-9 months a year effortlessly. If they moved another 1000km north they could eat wild fruit virtually all year.

  24. Hi John, thanks for the link, which provides lots of food for thought. But if uric acid levels go down on a ketogenic diet, and uric acid is a necessary antioxidant whose plasma levels correlate with longer lifespan in humans, how do we interpret this?

    Maybe a ketogenic diet still has to be punctuated by periods of high fructose. As blogblog says, an HG can get a good amount of fructose if he looks for it. Is he looking for it every day though, or is it just a supplement for occasional lean times? In the case of the latter, eating fruit could be a great signal to the body to get stronger and more efficient so you can survive until the next hunt/get through the drought, etc.

  25. Geez gunther, first you propose glucose being helpful because it lowers uric acid, now you question OD/keto because uric acid isn't high enough?!?

    ...jk, jk, I'm not really sure, so I'll defer to Peter...

  26. off topic: another reason to not eat plants?

    "A patient who feared he had cancer was told he had grown a pea plant which had sprouted leaves in his lung."

  27. John, I'm starting to think of a lot of former "poisons" differently now that they're in the context of a diet of 100% Real Food.

    Perhaps in a paleo/Real Food context, fructose and other plant compounds become essential elements for periodic cellular "house cleaning"? Purposes and uses can change depending on the metabolic environment of the person ingesting the stuff.

    Kind of like cardio seems to make those on the SAD fat and enable inflammation and other metabolic syndrome disorders, but for anyone eating Real Food, that could easily not be the case.

  28. An epidemiological survey reported in Nutrition & Metabolism failed to find an association between fructose ingestion and hyperuricemia in quartile comparisons, while finding a link between alcohol and hyperuricemia. This suggests that this pathway is not invoked at levels up to 64 gm of fructose per day. I can believe that with decile comparisons some effect would have been found at, say, above 150 gm per day.

  29. HGs are opportunistic eaters. Some Aborigines in eastern Australia ate nothing but huge quantities of Bogong moths for weeks at a time each spring. Likewise HGs probably gorged on fruit when it was available and then ate no fruit for months.

    HGs also would alternated between priods of very heavy physical activity and being totally sedentary.

  30. Hi gunther. I read a paperer which suggested that fructose is a metabolic signal to store fat for the winter.

  31. Let me state for the record that I don't doubt that fructose makes you fat, and that it is certainly bad for you when eaten in high amounts chronically. But perhaps in paleo-pattern bursts, and given an otherwise healthy body, it has a different effect.

    Random restriction and abundance is a major fact of HG life. Maybe analysing things in such an absolute, steady-state way is not the way to go. I mean, look at what happened with jogging, vegetarianism, fish oil, protein shakes and now low carb. Isolating any one factor doesn't seem to bring real health. In fact in some cases it is a detriment. Fructose evolved alongside us just like saturated fat did, so even we ODers may have to admit it has an essential role to play.

  32. Yes, Hunter Gatherer, let the hormetic principle rule. Challenge your hormonal and enzymatic homeostasis from time to time and upregulate another sub-system.

    The results are more likely to be explained by non-linear dynamics and give rise to a different set of Mandelbrotian fractals.

  33. Until the mid-19th century northern European peasants went to bed in November and stayed there until March or April to avoid fatal starvation.

  34. Gunther,

    The uric acid paper is interesting indeed. And it does tie in to free radicals and beta oxidation nicely, the signalling role of free radicals and when they might be good or bad. Reminds me of the worms in the "live long and prosper" study.

    I guess how you term this, ie hormesis due to stress, or looking at the superoxide radical as an intracellular signal, reflects whether you regard fruit as a toxin which is potentially beneficial or simply sends a signal which needs some adaptation made to blood urate levels which then stops oxidative damage.

    I would agree completely that the physiological response to many things depends very greatly on the background state of the organism. My problem is that there is no data on all sorts of things, like smoking (which is very bad news on the SAD) under LC circumstances. Reaven suggests that the problem from smoking is aggravation of metabolic syndrome due to release of FFAs by nicotine in the presence of glucose. Might this be OK if you don't eat (much) glucose? And from the Drinking Man's Diet and a ton of work on rats we know that PUFA avoidance markedly reduces the problems of alcohol over consumption, especially if carbs are reduced..... Oh, and perhaps fructose is perfectly OK in a LC/low PUFA environment in the same way?

    John, I can't even see the abstract.... but why shouldn't uric acid reduce if you are on a ketogenic diet? Presumably if you burn fat you generate free radicals and activate SOD and GPx production...... Less need for a systemic antioxidant? OMG perhaps ketogenic diets make you stupid???? Arghhhhh!


    I read an interview with a pop idol from Iceland, name escapes me at the moment. She suggested they spent 6 months in bed each Winter in Iceland. "What?", asked the interviewer "you go to bed and sleep for six months?" "Who mentioned sleep?"

    Might not work.


  35. Hi Peter, whether fructose can be used due its hormetic effects or because it creates oxidation which summons a dampening effect from the cells (which is exactly why exercise is good for us) doesn't diminish its possible practical use. And as we know, it's been "used" for millions of years by humans.

    Also, we shouldn't leave out the possibility that there are millions of gut bacteria populations that respond immediately to the particular kinds of sugars (fructose, glucose or galactose) you give them by changing their population balances and signalling the body accordingly depending on which bacteria are outnumbering which.

    Given how little we know about them, but assuming they are much, much older than us and their amazing ability to manipulate their hosts, this could be enormously significant.

    Maybe fructose, in a body without the dysbiosis typical of the SAD, causes certain good gut bacteria to thrive and outnumber the bad ones. Untestable and unprovable, you may say, but worthy of consideration nonetheless.

    You didn't mention my point about differentiating between sugars. Sucrose is much harder to find in the wild, while HGs seem to eat their glucose and fructose pretty separately from each other (except maybe in present-day pineapples, but I don't know what they used to be like in paleo days).

    Do you think there's any reason to believe isolating glucose from fructose is a major factor we've missed? Their uses, origins and metabolism are so different, it begs the question. Don't forget that HFCS is anywhere from 30 to 70% SUCROSE, depending on the purity level the soft drink company chooses to use. I'm not advocating eating HFCS, just trying to lay some of the blame for our present day metabolic syndrome epidemic on high amounts of sucrose too.

  36. Peter, I don't have it either. I was just forwarding a quote from the paper from someone who did have it. Ha, I hope it's not making me stupid...

  37. This comment has been removed by the author.

  38. Peter and Gunther,

    Any thoughts on or familiarity with the Specific Carbohydrate Diet?

    This is where you only consume carbs as monosaccharides, not disaccharides or polysaccharides. So no sucrose, lactose, starch, grains, etc...

    It's supposed to ensure efficient and complete intestinal absorption of sugars with nothing left behind to feed gut bacteria. Looks like it's mostly promoted to help with IBS/Crohn's, but there are reports of it helping with autism and skin problems as well. As I understand it, the idea is that any complex sugars that aren't quickly digested and absorbed will lead to bacteria (even the friendly kind) producing acid which irritates the lining and opens tight junctions leading to autoimmunity.

    So an interesting point is that only butter and fermented dairy/cheese is allowed. Yogurt must be homemade and fermented for over 24 hrs, although you can use Dannon or Total Greek as a starter, but none containing bifidus. My eyebrows went up when I read that, since Emma said the same thing awhile ago at PP&RS:

    Personally I had stopped eating yogurt over a year ago because it seemed to make my eczema and allergies worse, but looking back at all the brands I was eating then (Trader Joe's, Whole Foods, Brown Cow) they all contain bifidus and some had other untraditional strains like B. Infantis or L. Casei. I am doing great on the more traditional, homemade stuff.

    My experience following SCD so far is better digestion and better tolerance of fruits and vegetables, especially nightshades. I am still LC, but a peach or plum now and then and enough honey in my yogurt to stay out of ketosis. Honey is the only sugar allowed since it is an invert sugar and the sucrose is split apart. Dextrose is warned against for purity reasons, but I think you could find pharmaceutical grade, which should be 99.9% pure, if you really wanted to avoid the fructose. But I prefer the taste of honey in my yogurt...

    Definitely makes me think you are right on Gunther, about sucrose being hard to find in nature. I might go further and argue that before civilization, all complex sugars seem to have been very rare commodities.

  39. Hi Owen,

    I certainly point everyone in the direction of the SCD for their choices in carbohydrate if they have either overt IBD of any sort or auto immune problems that really can't be messed with, like MS.

    SCD is not intended to either be long term or LC but obviously there is no problem with either additions if that's the way your outlook directs you.

    Once you correct the dysbiosis that causes IBD Elaine Gottschall was quite happy for the SAD to be re introduced gradually, which makes me suspect that intestinal dysbiosis might be core to IBD. A little sucrose seems fine once you have normal gut flora... I've loaned her book to a friend so can't check if she eventually reintroduces gluten, but I think she might. Obviously my biases are set against this but I agree with her food choices for managing IBD very closely.


  40. Owen, maybe what I said about discriminating between fructose, glucose and galactose goes further then.

    I was talking just about not eating fructose and glucose at the same time because of the conflicting signals they seem to evoke in the body. Your comment made me think that there are implications of the actual structure of the sugar molecule as well, ones which effect the bacterial population in the gut. It does seem we evolved with mostly monosaccharides and not very many disaccharides or polysaccharides in our diet.

    So my question now is: is sucrose, a disaccharide combining fructose and glucose, just as bad as, say lactose, a disaccharide combining glucose and galactose? As we've seen, sucrose is pushing uric acid up and down at the same time. Is lactose doing that too, or is lactose just bad because it's too complex for the gut to absorb (according to the SCD)?

    Maybe we need to be watching the timing between the sugars we ingest as well as their chemical structures. The implications this has for lactose is weird though: As Peter says, why would a cow produce a substance to destroy the gut of its calf? Doesn't make evolutionary sense to me.

  41. Gunther, galactose is handled differently to fructose by the liver and in IBD lactose is bad when used by dysbiotic bacteria to proliferate. Under normal bowel microbiota conditions, especially in neonates, lactose is utterly beneficial, otherwise it wouldn't be there... In adults it's negotiable perhaps, but in neonates it's all good.


  42. Gunther,

    In the scope of the SCD lactose is viewed the same as sucrose, but I would imagine it's the more problematic of the two as far as having a less likely chance of being effectively broken down into the two monosaccharides. You never hear of sucrose intolerance as a general problem the same way you do with lactose...

    But as Peter said, Elaine's thinking seems to be that once the flora corrects, you can reintroduce these more complex sugars slowly. I don't have the book, but I think the timeframe is about two years.

    The interesting line of thought I got on to was that beyond the idea of "good" bacteria and "bad" bacteria in your intestine, is that starving all bacteria of complex sugars might be helpful. L. acidophilus and L. bulgaricus will both produce lactic acid in what is supposed to be an alkaline enviroment if you give them enough sugar at that point... whereas eating this acid in yogurt will be neutralized at the same time stomach HCl is. I wonder how much of a problem this causes, beyond those with IBD, in any person?

  43. Owen,
    apparently sucrose intolerance is realtively common amongst Inuits - with the same symptoms as lactose intolerance.

  44. You might want to know that the president of OSBO (Optimal Association) has died today of stomach cancer. He's been fighting it for the last two years.

  45. Hi _Flo,

    That is very interesting. I have been thinking about your email from a year or so ago about this person and others within the OD community, and failed to get anywhere with what it might mean on a personal or overall basis. There are some things we know and some things we don't. This one is a salutary warning that no one gets out of here alive and no one has all of the answers.

    I am personally stuck with the health improvements I have from the OD and my family history of colorectal cancer. I am well aware that the OD as we eat it in our household is not perfect as I keep getting reminded by poor migraine control and hyperemesis of pregnancy in my wife. But when we have discussed any sort of radical change to diet it always comes with the potential of losing the huge benefits we have already accrued, especially in gut function.

    It's one of those pieces of information which I file for attempts to integrate in to how the world works. At the moment it is not obvious how it fits and I keep it in mind as I accumulate information.

    Thanks for the reminder.


  46. Kwasniewski doesn't eliminate gluten or grains, nor sucrose. He also doesn't address paleolithic foods, dietary lectins, monosaccharides vs. polysaccharides, intestinal dysbiosis, EFAs or omega 3 to 6 ratios. I think these are essential dietary factors he has missed, which would have major impact on anyone's cancer. In short, the OD as written is not perfect, which is exactly why Peter has tweaked it.

    And as an aside, do we know when the president of the OD association actually started the diet? Maybe he had cancer before. Maybe he didn't even adhere to the diet. I always thought Atkins was overweight when he was alive, making me suspect he didn't follow his own precepts...

  47. Gunther, I am very aware that the diet which I eat is not perfect either. But these things do need consideration. I am also pushed to consider the implications on all sorts of fronts. I certainly have no details of the type you mention, but I have some general principles I work to. I'll see about a post along these lines.


  48. Peter,

    What do you consider a "radical change to diet"?

    ...not high fat?

  49. Hi John,

    We discussed increasing paleo carbs to over 100g/d for my wife to attempt to manage her migraines. These seem to be a parasympathetic dominance problem and I was thinking about increasing sympathetic tone with the carbs. That would need some calorie counting to control weight. Not sure it would have worked and we never tried it. It's hard to give up the gains you already have...


  50. ...oh no, from the author of Hyperlipid! Did you consider/try changes other than macro nutrient proportions? Although you are probably already aware...
    *migraines and estrogen
    *retinol inhibits aromatase activity in vitro

  51. Hm, I don't know what to tell you Peter. I myself am rather disillusioned regarding the diet itself. And probably biased against -- as I've got the feel of the community and its leaders.

    If you would like some details: the man was 64, on OD for 12-14 years, diagnosed 2 years ago, reported in good health before that. He was one of the participants in prof. Pilis' study (
    The impression we get is that there's rather high occurrence of gut cancer, including stomach, duodenum, colon...

    I myself don't follow OD any more, less yolks, less fat (1.5g per kg), esp. less saturated, much more veggies and some fruit, little dairy, low calorie, no frying, very little cooking, mostly iberico & serano ham, some grassfed raw liver (I know :P). Generally - I'd like to call it 'a balanced diet', paleo-style :D

  52. ...Also, there are accounts of raw carrot helping. If it's not the "vitamin A," it could be the pectin/fiber...
    *increase in fecal volume=increase in estrogen excretion (I'm unsure as to whether fecal volume is more to do with bacteria growth or fiber--but it doesn't matter)

  53. sorry, 17 years on OD, not 12-14

  54. _flo,

    I know how you feel, but there are so many variables that we need to control--maybe. How do additives in salad dressing, dairy, spices, etc affect us? What about the many "unnatural" chemicals perverting most plants? I actually feel safest about the foods you mentioned you decreased (saturated fat)! It's so difficult to get a good idea of what these people (failed ODers) were eating.

  55. Sure, this case is a lot like an observational study, and very limited at that. But one has to consider these facts and try to connect the dots.

  56. Hi John,

    I've not followed the links yet (got to work soon, should do later) but as a general principle I like to carry the possibility in my head that my hypothesis is wrong. Without this I would be lost. I go through the literature and see no suggestion of low fat eating improving the host of medical problems helped by low carbohydrate eating. So I eat LC. But so little is known about LC eating in an industrial food settling on a long term basis that you absolutely have to keep an open mind.

    _Flo has listed some of the points she has considered and acted on. You are both correct that we are in an observational situation and have to assume it is going to stay that way for a very long time.

    We have just been given a piece of information. It is not for discarding through cognitive dissonance. What we do with it is our own choice.


  57. In an industrial environment, eating 80% non-grassfed, non-organic animal fat, you are definitely ingesting a fair amount of toxins. Maybe a lot of toxins actually.

    I think the quality of the animal fat you eat on the OD is a major factor too. If you're gonna eat grain-fed, hormone-and-antibiotic-pumped animal fat, you might as well eat the SAD.

  58. It seems to me that the oxidative stress when the muscle cells use fat as fuel. If it they use glucose, its initial metabolical step, glycolysis, happens outside mitochondria. The corresponding fatty acid β-oxidation happens in mitochondria. I'd guess the mitochondria are much better equipped to cope with the oxidative stress than the rest of the muscle cells. However, if the oxidative stress drives mitochondria to multiply, the outside and inside stress might work differently.

    Another difference is that under anaerobic conditions the muscle cells can use glycolysis without feeding its end products into mitochondria. Instead the end products get converted into lactic acid. I wonder if there is similar anaerobic oxidation process for fatty acids.

    The lactic acid seems to serve some singaling purposes, too. Lactic acid from fast muscle cells can be used as fuel by mitochondria in other muscle cells. (My training textbook claims that the lactic acid improves neural signaling to the muscles and protects heart from being overly stressed, too.)

  59. have you ever come across Bruce Ames' theory that the very high concentration of uric acid in humans (compared to most all other animals, including other primates) happened because uric acid is a powerful antioxidant that's cheap (free actually) to make - all you have to do to make it is not throw it away.

    High human uric acid, IOW, is a beneficial adaptation

    151 Ames, B. N., Cathcart, R., Schwiers, E. and Hochstein, P. (1983) Uric Acid: An Antioxidant Defense in Humans Against Oxidant- and Radical-Caused Aging and Cancer. A Hypothesis. In: Carcinogens and Mutagens in the Environment. Vol. II, Naturally Occurring Compounds, H. F. Stich, ed. (CRC Press, Inc., Boca Raton, FL), pp. 69-76. check for PDF

  60. Another of Ames' observations is that uric acid concentration in humans rose around the same evolutionary time frame that we lost the ability to synthesize vitamin C from glucose.

  61. All monkeys and apes have the loss of vitamin C production. I think the tarsiers are considered to be close relatives of monkeys and apes among primates because of the same mutation. On the other hand, lemurs and loris have retained the ability to make vitamin C.

  62. The problem with uric acid is that it's a catch-22. It's a powerful antioxidant which can lower chances of getting cancer, but it raises blood pressure and correlates with metabolic syndrome and heart disease. The best way to use raise it is with exercise, seems to me, then you counter the metabolic syndrome while reaping the antioxidant benefits.

    The theory is that we evolved uric acid to raise blood pressure as we started to walk upright. It may be what affords humans long life vs. their ancestors, but the gout/heart disease/metabolic syndrome aspects throw me off.

  63. My reading is that Urate levels below normal may be indicative of too many oxydating radicals around, while supra-normal levels are indicative of all the usual "diseases of civilisation".

    Paracelsus (or Bernard) Double Level Poison Principle - it's a Camel Shaped Response curve, got the hump.

  64. An eminent Australian cardiologist (whose name I have forgotten) said that dying from atherosclerosis at 60 was really just an evolutionary alternative to dying from a ruptured aorta at 20. His argument was that atherosclerosis was simply a crude mechanism used by higher primates to repair arteries damaged by the inability to synthesise vitamin C. This is very similar to the Pauling-Rath Hypothesis of CHD.

  65. This comment has been removed by the author.

  66. Hi gunther,
    the alternative argument for human longevity is that most babies in HG societies were fathered by realtively old men. Some Australian Aborigine groups only allowed men aged in their 50s and 60s to marry.

  67. if you're really lucky you will inherit Gilbert's Syndrome ("excessive" bilirubin production)- the only neagtive is a bit of jaundice and you are much less likely to develop MS, CHD etc.

  68. Hi blogblog,

    I just wikied GS and it does make fascinating reading. Amazes me that no one has developed a blocking agent for the glucuronosyltransferase enzyme.

    We could all become cats... oooh, obligate carnivores


  69. Hi Peter,

    with Adam Jany, president of OSBO, the second prominent figure of the Polish OD community died due to gastro-intestinal issues. Karol Braniek has gone before him at the age of 68. Presumably from duodenum cancer. Death in your sixties is not too encouraging, the SAD accomplishes the same.

    The question arises while being protective against those cancers that are driven by strong insulin- and IGF-signalling, could it be that OD increases your sensitivity against those forms of cancer that are induced by contact to toxic substances.
    Let me explain. Fat extremely delays gastric emptying. So any potential cancerinogen has increased contact time to the gastric mucosa where stomach cancer normally begins to develop. More time means more harm can be done. So it might not be a good idea to eat a sodium-nitrite loaden Presswurst along with your stick of butter.

    Decreased bowel movements is a frequent complaint of Low Carbers. Food transit time through your intestines is increased in this case. So the same mechanism can be applied to other organs of the digestive system. Just some thoughts...


    I was diagnosed with GS when I was eating a diet full of crap. Interestingly the slight jaundice has resolved after several months of OD. It seems that bilirubin clearing of the liver got better. Hopefully, the cardioprotective effect of GS is no longer needed.

  70. I do worry when all the recommendations are for grass-fed this and free-range that, as due to my budget I'm cheap mince, cheap pork, caged eggs and supermarket butter.

    Feel good on it and don't think I'd be better off on the SAD but still raises concerns.

    *sigh* it is what it is.

  71. Hi Peter,

    Dr Andrew Bulmer has studied the protective effects of bilirubin.

  72. Hi Winalot,
    the most important factor is to minimise carbohydrate consumption. I certainly won't pay extra for free-range, grass fed etc.

  73. I agree with the above, especially when dealing with ruminant animals. The omega-6 content doesn't differ between grass and grain-fed beef per serving, but omega-3 content is higher in grass-fed. You also have to consider that grass-fed is leaner, so you are getting less total fat per serving, losing 160 times the amount of monounsaturated and saturated fat as you are gaining in omega-3. I'm basing this off of a comparison between grass-fed ground beef and 80/20 hamburger (they don't list the lean/fat ratio for the grassfed, but I'm assuming it's the same...if it was 85/15, there's no way it would have as much o-6 as the 80/20 grain-fed):

    The grass-fed has 120mg of omega-6 per 28g serving and the grain-fed has 122mg. The difference in omega-3 is 11.2mg higher in the grass-fed. And the differnce in total fat is 2000mg less in the grass-fed.

    Personally I can't justify spending a lot more money for such a small gain in o-3 and large loss in total fat and calories.

    As for hormones, this seems negligible as well:

    According to the data, 6oz of non-hormone treated beef will have 2.6ng of estrogen; 6oz treated beef will have 3.8ng; 8oz milk - 34ng; 4oz cabbage - 2,700ng; 1 tbs soybean oil - 28,370ng; and an average adult male produces 136,000ng a day.

    I don't worry that much about antibiotics either:

    "Antibiotics may be given to prevent or treat disease in cattle. A "withdrawal" period is required from the time antibiotics are administered until it is legal to slaughter the animal. This is so residues can exit the animal's system. FSIS randomly samples cattle at slaughter and tests for residues. Data from this Monitoring Plan have shown a very low percentage of residue violations. Not all antibiotics are approved for use in all classes of cattle. However, if there is a demonstrated therapeutic need, a veterinarian may prescribe an antibiotic that is approved in other classes for an animal in a non-approved class. In this case, no detectable residues of this drug may be present in the edible tissues of the animal at slaughter."

    That's not to say I think any of this is good news or nice for the cow, but that's a different issue then...

  74. Another point that occurred to me is that from my perspective on food, something like beef is going to be a bulk food that I use for calories, protein and fat. So if it turns out that 10 servings (280 grams) of 80/20 grain-fed ground is what I find satisfying for dinner, and then I switched to grass-fed, I would have to add extra servings to achieve the same level of calories and fat. The problem here is that not only do I increase the cost even more of an already expensive dinner, but I add 5 grams of protein (which at this point is probably not needed) and 120mg of omega-6 per 28g serving.

    On the other hand, I suppose these comments don't really apply as much to grass-fed milk or butter, which may be more expensive, but otherwise consistent in calories and total fat to the standard versions.

  75. Owen and Winalot,

    When I made the comment about the harmful effects of grass-fed organic vs. industrial, grain-fed fat, I was referring to the amount of toxins that reside in the fat of the industrially raised animals, not the omega 3 to 6 or other ratios.

    Environmental toxins are stored in fat, so naturally if you're eating lots of animal fat, you should be eating as much organic fat as you can find, otherwise I don't think you're helping your health.

  76. Also, any reports issued by the USDA are not to be trusted, since it and the FDA staff are all former directors of food corporations, who get kickbacks from their cronies in the industry every time they say what it wants to hear. They are not a legitimate government agency, but just the PR wing of big agro and other businesses.

    If you read a report from them, you might as well read a meat industry press release.

  77. Peter,
    you mentioned hyperemesis in pregnancy. I read (in a book about cancer) that amylase can help morning sickness because the fetus does not produce amylase which helps break down the glycoproteins in HCG so the mum 'over-uses' her enzymes and that throws off her balance and makes her ill (my version is way over-simplified).
    Have you heard of that?

  78. Peter, THANK YOU for this blog! I'm not a scientist, so I can't contribute a lot, but I've greatly appreciated the level-headed information I've found here.

    My "gut feeling" is that you are definitely on the right track with your version of the OD. My insides are quieter than they've been for a very long time now that I've tweaked your version a bit for my own needs.

  79. Hi, Winalot.

    Some thoughts that might be useful: I think all that any of us can do is to study and learn, and sift and sort, and go with what works for us. Both the human body and the food we eat are so complex and variable that I doubt there will ever be a time when anyone can say "X food will always have Y effect on everyone who eats it."

    Not everyone is convinced about the need for EFAs. In his book, "Trick or Treat," page 104, Barry Groves has a section titled "How essential are EFAs."

    Nor is everyone of one mind regarding toxins in our food. Christian B. Allan writes, "Other people believe that the increasing use of artificial fertilizer, pesticides, and insecticides has led to the increase of many of today's modern diseases. This is a reasonable idea, but has it been proven or is it just an opinion?" ("Life Without Bread," p. 9.

    I buy grass fed beef and eggs from free-range hens when I can, but if commercial meats and dairy are what's available, I use them and don't worry about it.

  80. Hi Owen / SilverThreads,

    Thanks for trying to cheer me up :-)

    As I mentioned, it is what it is, so I don't lay awake at night worrying over my budget fats.

    I know I feel and perform better than I ever did HC so that's what counts.


  81. Hi, Peter,

    I have been a lurker.

    this is the first time i am leaving a comment, cause i'm pretty disturbed by the news of the deaths of these the 2 leaders in OD.

    we just recently switched (due to "civilised disease" from so-called "healthful" diet)


    (our diet now is a cross between Weston & OD)

    thanks for the work.


    pam (not an MD)

  82. Hi Pam,

    We all have to make our own decisions. I hope I continue to keep thinking too.


  83. Hi Krissie,

    Not found that one. I would comment that the various problems my wife experiences appear related, migraines and hyperemesis go together. There are a number of aspects which tie together but I still have no coherent explanation...


  84. Peter,

    re. migraine, it is interesting that since i switched to hyperlipid diet (~50% fat, preferably SFA) since this year, i have had not a single migraine.

    but the new diet does not help much to tension headache, & other tension pain (shoulder, neck). (uh, too much computer)



  85. Hi Pam,

    My wife's migraines have changed but not gone. Slower, more persistent, perhaps less painful. Still unpleasant. Perhaps if we went fully paleo........?


  86. I thought the worst aspect of grainfed meats and dairy was the lectin content. If it's enough to prevent complete gut healing(1mg WGA per day, was it?) then there's an everpresent low level endotoxemia.

    And yeah, JK went a little Cordainish - sacrificed principles for simplcity and applicability. For all we know there's not a single person on Earth who is truly adapted to wheat.


  87. The Centre for Oxidative Stress Studies at the University of Queensland (where I studied) has published dozens of papers on the role of antioxidants, exercise and disease. All their research is performed on humans not rats.

    This research can be summarised as follows:
    - antioxidant supplements don't work
    - extreme exercise does not cause long-term oxidative damage

  88. Hi blogblog,

    Productive centre! Can't get at all of the abstracts but your summary sounds encouraging to a resveratrol skeptic...


  89. E. Coli can ferment ascorbate as if it were fructose; this may be the cause of "bowel tolerance" of oral vitamin C.

    "It has been known for over 60 years that various bacteria, including E. coli, can ferment l-ascorbate (l-xyloascorbate [vitamin C]) under anaerobic but not aerobic conditions"

    Also, some yeasts can produce ascorbate, possibly other microbiota species. Differences in microbiota might explain why there always seem to be some soldiers and sailors who are immune to scurvy in the historical case studies if the group is large enough.
    I don't think it's actually been proven that there is absolutely zero production of ascorbate in all humans under all dietary conditions. It's considered an axiom not in need of proof, I guess. Us lacking that one essential gene need not rule out non-enzymatic reactions or alternate pathways in specialised tissues, under particular metabolic conditions, or the microbiotic option.
    Also, how much ascorbate do you need if the diet is rich in carnitine, hydroxyproline, creatine and anything else for the production of which ascorbate is essential?

  90. I am also proud to be a resveratrol skeptic. In fact I hate the stuff, it gives me neuropathy. I don't see how concentrating it wildly out of its natural ratios can be good in the long term.
    However: I feel the whole hormesis theory of polyphenols is a dead end. You might as well say that pharmaceuticals work through hormesis. No doubt a bit of that goes on, but it's missing the point. There are pathways besides detox enzymes that they affect.
    HGs seem to always be chewing twigs and leaves with no real nutritional content.
    The induction of detox enzymes by polyphenols influences the metabolism of estrogen and testosterone. Eating grapefruit doubles the risk of breast cancer in women at high risk because this polyphenol inhibits estrogen detox; which could be a life-saver if the risk is liver cirrhosis instead, something estrogen protects against.
    It's a huge field and I can't do justice to even my meagre knowledge of it in a comment, anymore than you can by citing hormesis. Hormesis, when applied to compounds as specfic in their actions as polyphenols, is a philosophical concept more than a medical one.

  91. This comment has been removed by the author.