Saturday, September 21, 2013

Wooo and the snps

There seems to be quite a bit of interest going on in the LC Hardcore at the moment and I'm sat here, under my stone, looking at UCPs as prime mediators of the insulin resistance of fasting and membrane pumps in the origin of life as relates to lactate and extracellular pH in cancer. And I should really be working on a dead-lined anaesthesia project. Wooo and Toxic ("I read your potatoes, and the news will never be good" LMAO) have both brought up 23andme and, surprise surprise, Wooo has enough snps on assorted ion channel genes to have her in a loony bin several times over. She concludes that a ketogenic diet gets her a normal life.

Obviously I have nothing to disagree with here.

What I would comment on is that a very, very large chunk of the "normal" population may not be quite as normal as she suspects. Having frank bipolar disease with severe enough presentation to give you a clear cut "label" is quite rare. Having severe depression to the point of complete loss of functionality or schizophrenia to the point of obeying the voices completely, whatever they command, are all equally rare. But shades of grey appear to be very common and I don't see that many normal people are all that normal. Undoubtedly we all have snps on all sorts of genes. That's genetic variability and is essential to provide a pool for the species to adapt through.

That many mental illnesses are essentially metabolic, and that ion channels have a great deal to do with neural energy demands, is not exactly unexpected. Sid Dishes emailed me this rather interesting review (BTW finding this in Nature is rather like reading a massive endorsement of the Atkins diet in the Sun or the Daily Mail, Sid feels paradigm shift) looking at exactly the metabolic aspect. Yet another email needing a thankyou not sent yet. Thanks Sid. Look at this quote from the abstract talking about central neurons:

"it is now clear that they [psychiatric illnesses] are associated with impairments of synaptic plasticity"

and tie that back to peripheral neuropathy, here's Chowdhury on peripheral nerves:

"The consequences of suboptimal ATP supply for the distal nerve fiber are numerous: (1) collateral sprouting and plasticity will be retarded, (2) this will lead to gradual pruning of the axonal network and shrinkage of sensory innervation fields, and (3) end organs of myelinated fibers within the dermis will lose innervation and function (see Fig. 3)"

My italics.

The parallels, to me, make it sound like we are talking about the same process. I would suggest that hyperglycaemia breaks the mitochondrial population and ketosis is an excellent sticking plaster. Which snps you have determine which neurons break first.

If you also have metabolic snps which limit your ability to avoid hyperglycaemia on the SAD in addition to neural snps which make for "upper limit of normality" energy demands within hyperglycaemia compromised neurons, you are on your way to the Funny Farm. Or a ketogenic diet.

I, for one, am very glad Wooo hit the ketogenic diet arm.

I have said that I think it is unlikely that humans are in any way adapted to a diet which regularly and severely induces hyperglycaemia. Had Wooo been born in to a normoglycaemic environment, what would the effect have been of her ion channel snps on perception?

If you think Wooo is "normal", you are crazy.

Personally, I think we need people who are three standard deviations from the population norm when it comes to insight and perception. This may well be down to ion channels and snps of the Wooo flavour... I don't see that we would get too far, species wise, if we were all Taterheads with ion channels which allowed tolerance of hyperglycaemia until Alzheimers (type 3 diabetes) kicked in, and yet only allowed as much insight in to anything as a turnip has. Of the latter, there is a lot of it about, we have more than enough.

Blog on Wooo.



Anonymous said...

Peter, thanks so much for sharing your thoughts. I’ve been following Wooo (of course) and I think she is so utterly normal and unadulteratedly (is that a word?) human, that I must be crazy :-). After reading Anna, and finally realising that a Pleistocene environment without any meaningful carbohydrate supply really seems to be our ‘normal’ habitat, the simple thought dawned on me that most ‘genetic abnormalities’ of today must be ‘benign’ or even advantageous under normal, Pleistocene conditions. Take this ‘breast cancer gene’ which the cancer business so eagerly exploits. In our world of bagels and pasta it ‘causes’ breast cancer (which it actually doesn’t, it increases the risk for mitochondrial dysfunction under abnormal circumstances), in a ‘normal’ world with many beasts but hardly any edible plants it just produces super fertile women. Wooo’s ‘abnormal’ genetic make up makes her a bit unbalanced or worse in our modern grain and sugar based zoo, but the same set of genes probably produces extreme creativity and allround smartness under evolutionairy normal conditions. Which she fortunaltely recreates.

A lot can be learned from this.



Galina L. said...

I wonder to which extent mental disorder are among the cluster of diseases of our Western Civilization. The metabolic connection is very strong, besides, there is a tendency nowadays to mistake metabolic condition for a mental one. I personally know at least two people who are treated with anti-anxiety meds for the symptoms of a hypoglycemia. In one of such cases a hypoglycemia is even officially diagnosed. In my own case the severity and frequency of migraines absolutely correlates with gaining weight, frequency of infections and susceptibility to allergies. OK, I was lucky enough to be able to just walk into the medical testing lab right when I was having one of migraines, and it was found that I had an abnormal epilepsy-type electrical activity in my brain. Few people have epilepsy with seizures(abnormal people in public opinion), way more suffer from migraines(normal ones). The standard way to prevent migraines is taking an anty-seizure medication which is also used for mood and bipolar disorders. I bet a good portion of migraineurs are actually epileptics without knowing(grey area), if the criteria is their electroencephalogram. They are far from being dysfunctional, there are a lot of famous talented people know to have either or both migraine and epilepsy, most famous of such people is probably Julius Cesar. There is also a well-explored connection between artistic abilities and bipolar disorders.
It looks like people in a grey area have an advantage of being able to function at higher level, but have a price to pay in the form of having less than iron health.

Sabine said...

Peter, I like your take on things.
Nature knows what she is doing.

James said...


Peter said...

Melchior, I would just like to share a correction pointed out to me on a previous occasion by Stan (Heretic). A minimally carbohydrate based diet is intrinsically a low fertility diet. In my early LC days I recall being puzzled by reduced litter sizes in zero carb fed bitches. This is not a criticism of LC, sub maximal fertility is probably the ideal. No HG population would want a child per woman every 11 months. Maximal fertility looks to be a feature of high carb diets and the advent of grain based food may well be associated with an explosion of (hungry) people. Even Lutz's work with chickens suggests you can dial the egg yield by the fat:carb ratio of the diet, more carbs = more eggs. LC may be therapeutic in PCOS, but PCOS is pathology... Nick Lane discusses the trade off between reproductive efficiency and longevity. My ex battery chickens have a depressingly high mortality, they come to me "worn out" from "supramaximal" fertility. I just keep replacing them.


Puddleg said...

I agree that mood disorders, schizoid symptoms etc. are far more common than assumed. When they peak in adolescence and early adulthood then resolve with maturity, they may never be reported - or even properly remembered.
As to their adaptive value, an enjoyable early perspective on this is in The Clans of the Alphane Moon, a 1964 novel by Philip K. Dick.

fredmull said...

George, I would imagine volumes of books could be written on school-shooters/mass murderers, their psychosis and the high- carb/vegan diet they eat.
Imagine a world where LCHF turns us into a utopian society!

fredmull said...
This comment has been removed by the author.
Jonathan said...

A minimally carbohydrate based diet is intrinsically a low fertility diet.

Peter, it's interesting that you say that. I recall Dr. Michael Eades mentioning in the comments of one of his blog posts that when he and his wife still had their practice, scores of their patients who were having trouble conceiving would suddenly get pregnant a few months after the good Drs. put them on a low-carb diet. Were all these patients suffering a pathology?

Peter said...


"that I must be crazy :-)"

All the best people are...


Peter said...

Jonathan, I would imagine very few people would consult Dr Eades unless they have a metabolic problem.


ItsTheWooo said...

Thank you Peter; this blog entry was both very interesting as well as a kind sweet gesture of support.

Regarding fertility and a low carb diet, I agree with Peter entirely. women without an endocrinopathy may observe reduced frequency of ovulation...women with pcos observe the opposite because a primary defect in pcos is hyperstimulation of ovaries via insulin and this LH excesses. A lc diet reduces insulin, thus the pathological lLH that leads to ovulatory failure.

Jonathan, if someone has been trying to conceive for years unsuccessfully this is a primary symptom of anovulation and pcos. Likely does not apply to normal fertility women who can conceive on a high carb diet.

John said...
This comment has been removed by the author.
Peter said...

Wooo, this is how I view the world...

John, I don't really understand the comment.


John said...

Oh, I was just wondering if wound healing is impaired somewhat on low carb. I think I saw that the MRL mouse has a high/low rate of glucose/FA oxidation, and it also has excellent healing/regeneration. It isn't the same as aging, but maybe there is a little overlap.

mem said...

Check out John Ratey's book: Shadow Syndomes.

Peter said...

John, OK, I think healing would go particlularly well under LC. Hyperglycaemia and a metabolic set up which is pro inflammatory will give poor wound healing. I would expect it to be a cause of the common allodynia found in surgical wounds. Normoglycaemia and palmitate will let the immune system/wound healing do its stuff.

mem, hadn't seen it but comes as no surprise... Ta.


SS Biker said...

+1 Blog on Woo - There's gold in that there crazy (both comedy and factual)

Re: John and his question

Poor diabetic wound healing due hyperglycaemia is well documented of course. Hyperglycaemia =/= LC but my n=1 is that LC has not caused me noticeable changes in wound healing either way.

However I would say that since adopting a low carb/reduced PUFA diet I have noticed several "skin" related improvements, which I suspect are related to the PUFA reduction more than anything.

To whit: I tan more evenly and seem increasingly resistant to sunburn.

I seem less sensitive to skin irritants and reactions to insect bites are different. Before LC/Low PUFA I used to react to insect bites with small/hard swellings with small central blisters that itched intensely particularly if scratched or immersed in hot water (i.e. bathing) - they could remain sensitive for up to 2 weeks in some cases.

Since adopting LC/Low PUFA insect bites are much less irritating and shorter lasting, however about half seem to to develop into a way over the top swelling and blistering which inevitably burst and continuously weep goop for a day or two (quite difficult to manage in fact). They itch but not as bad as the "small angry" bites I used to get and they still clear up quicker.

I may be an "odd case" as I had Uticaria Pigmentosa as a child and may still have a heightened histamine response, but have otherwise only seen positive changes since going LCHF (low PUFA).

Oddly I was talking to a friend a while back who was concerned about thread veins (visible blue/purple veins in their ankle/foot area) and in particular that he was worried that he was going to get an ulcer or some-such in one particularly bad area. For a long time I had been aware that I had similar (but no-where near as bad) veining in my ankles too but after this conversation I “had another look” and this veining appears to all intents and purposes to have completely disappeared. I have no idea when this happened, as I wasn’t particularly conscious of it but I can only assume it’s since I altered my diet (about 2 years ago in a progressive fashion).

Toxic said...

Oh oh, I've been mentioned in dispatches.

LOL at low carb hard core lolololol.

It's a new world, isn't it? It's a topsy turvy world where the patient goes in to the doctor armed with the kind of data that seemed exotic and space age five minutes ago. As if the internet weren't torment enough to the hapless GP, now we are going armed with our actual genome - every last piece of DNA in our bodies.

I think this will change medicine fundamentally. Geneticists will be in every surgery. Once we have sufficient data to know which snps will do what and under what environmental circumstances, ordinary doctors will become pretty redundant except for fractures. We will be feeding in our genome into a punch thing on the wall, and our tablets will come out a chute at the other end. Or a steak slathered with mayonnaise... in the better surgeries ;)

Peter said...

Toxic, yes. But you have to have certain qualifiers. You need a framework to deal with the information. What would a Taterhead do with the information available to Wooo? In a Normally distributed population most people would have no concept of what do do with their snps. Booking a executive grade Funny Farm place if you have psychosis snps? Investing in new pharma med research? Ketosis to patch your mitochondria, now go wash your mouth out with...


Bill said...

I'm still not entirely sure where I stand on the Wiley/paleo/"seasonal breeding" hypotheses, but in that paradigm, breeding season corresponded to a time of increased carbohydrate availability.

The effect of low carb on fertility would've been irrelevant because they weren't trying to conceive in the dead of winter.

Again, it's just a theory, but it keeps on *making sense.*

LeonRover said...

"Again, it's just a theory, but it keeps on *making sense*."

The theory that prescribing menopausal women with hormones *made sense* until studies & measurements showed it *made non-sense*.

Likewise the theory that poly-unsaturated & hydrogenated fats were healthier than saturated fats *made sense* until studies showed otherwise.

The theory that interfering with HMGCoA pathway *made sense* until this

study showed it *made non-sense*.

Theories can be intellectually seductive; it is only data and results that make science.


Ilaine Upton said...

The only way I could heal my diabetic foot wounds was a ketogenic diet. But then, I have diabetes. This may or may not be true for others.

When I was merely insulin resistant, and eating a ton of carbs, I had no problem conceiving, but I did not have PCOS. Probably. I had some of the PCOS symptoms, facial hair, acanthosis nigricans, skin tags. I guess the way to demonstrate that I did not have PCOS is that I had no problem conceiving, which may be something like a logical fallacy, or maybe not. I did have gestational diabetes.

Almond said...

I think the "a-ha" moment came for me when I realized that most diseases (both mental/phyiscal) are not this incredible, separate "things" that people wake up to one day and find themselves sick with. It is so eye-opening. And I'm learning so much from this blog, so thank you.

LeenaS said...

"Theories can be intellectually seductive... "

Oh yes. The seductive power of theories has been shown even experimentally. This is why it is so hard to do good science. Seduction, covered with money, is there. Everyday and everywhere.

Thanks, Peter, for your blog!
With regards,

LeonRover said...

"Seduction, covered with money".

Just lead oneself to the money.


Anonymous said...
This comment has been removed by the author.
Peter said...


One of my earliest vinyls...


archandevo said...

Peter, I agree with you furiously that maximal fertility is sub-optimal and a product of Neolithic/high-carb/evolutionarily inappropriate nutrition. In starch consuming Neolithic communities, fertility peaks very early on in a woman’s life and remains switched on, even under poor nutritional and environmental conditions. The mother breastfeeds for a much shorter length of time (approximately 1 year) allowing her to fall pregnant again much earlier. Such early fertility takes its toll on longevity: insulin stimulates cellular proliferation and amps up reproductive energy at the expense of the individual's own restoration, maintenance, and repair, leading to earlier mortality. More prolific reproduction occurs at the expense of provisioning humans with the essential components to sustain and prolong life, ultimately engendering trade-offs between survival and reproduction. The Neolithic population expands exponentially, to the community's detriment. Longevity is severely diminished and mortality rates skyrocket.

In contrast, HG communities experience comparatively low fecundity compared to current Western populations (seen in the !Kung San; Hadza; Dogon, to name a few). Contemporary women consuming SAD style diets experience three times as many menstrual periods as women from HG communities. Eaton and Eaton reported that, on average, HG women are 16 years old at menarche and 19 at first birth. They subsequently nurse for 4 years, and experience menopause between 38 - 47. What follows can be understood as crucial late-life phase where the adult is still essentially ‘reproducing’ through caring for immediate offspring. The human child demands substantial and protracted care it its upbringing; consequently, an infertile adult caring for offspring can still be considered to be of evolutionary value (i.e.: the Grandmother hypothesis). As female reproductive function can be said to extend past menopause, human longevity (as is commonly witnessed in HG populations) has measurable function. Hunter-gatherer populations demonstrate a short periods of ageing with lengthy and sustained mortality and fertility plateaus. Michael Rose has written extensively about this so I won’t say anymore here except that maximal fertility is not conducive to longevity nor is it evolutionarily ideal. Implementing hunter-gatherer (i.e. low-carbohydrate) patterns of nutrition in contemporary populations might lower fecundity but it will have the (invaluable!) advantage of allowing us to slow later ageing and possibly hasten its cessation.

Paula said...

Pretty good post about depression

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