Arguments for a Soda Tax are sometimes based on the specific metabolic effects of fructose, but for most people these effects are only slightly more stressful than the effects of glucose, and probably not worth worrying about too much. A more convincing argument to my mind is that sugar availability promotes overconsumption of energy, and carbohydrate energy in particular. Not to mention azo dyes and similar unappreciated toxins, which are mainly consumed associated with sugars. This allows the sugar industry to say "it's the calories" when analysing the data. But does restricting sugar make it easier for individuals to select a nutritious diet without overeating?

Dietary Instinct, by John Yudkin(from the Penguin Encyclopaedia of Nutrition, 1985)

It is sometimes asked "Why do we need nutritional advice?" Animals in their natural habitat, including our early ancestors, ate the foods that they instinctively chose, and those foods when available must be assumed to have supplied all their nutritional needs; natural selection would otherwise have insured the disappearance of the species. Why then does modern man need to be told how to obtain a balanced diet with fruit and vegetables for vitamin C, meat, fish, eggs, milk, and cheese for protein, and so on?
It has been proposed that this has arisen because man, with his scientific and technological skill, can make extracts from foods, mix them in varying proportions, add synthetic flavours and colours, and so produce new foods, more attractive and sometimes cheaper than many of the foods in their natural state. The qualities of attractiveness do not, however, ensure that the foods contain much, if any, of the necessary nutrients. As a result these new attractive foods may replace other and more nutritious foods in the diet and thus predispose to deficiency, or be eaten in addition to other foods and so predispose to the development of obesity. A further suggestion is that, because the most attractive new foods are those rich in sugar, they lead to an excessive consumption of this undesirable dietary item.
This approach to the question of what is a balanced diet lays stress more on what foods should be avoided than on what foods should be chosen. If the wrong foods are avoided, instinct will determine the amounts and selections from the correct foods. These are the foods than can be gathered, taken out of the soil, or slaughtered: the sorts of foods our ancestors hunted and gathered. They are meat, fish, eggs, fruits and vegetables; because of the constraints of pressure of population and of urbanization, it is usually necessary to add two of the foods introduced in the early days of the agricultural revolution, namely milk and cereal-based foods such as bread. Without these foods it would in many countries be difficult for the less wealthy to get enough to eat.
According to this argument, dietary instinct determines that we choose a food because we like it rather than because we need it. Dietary instinct cannot therefore be relied upon as an appropriate guide for a healthy diet when it is possible for the food manufacturer, and to some extent the skilled cook, to make foods that are increasingly attractive without regard to their wholesomeness or nutritional value.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Does dietary instinct work in captivity, which may be a realistic model for civilization?

In this study, rats self-selecting diet, from weaning to maturity, ate more protein and fat and less carbohydrate than rats fed standard chow.

In self-selecting males, protein intake was maximal at Week 7 of age and then plateaued (Week 13), whereas in females, protein consumption peaked at Week 7 and then steadily decreased. Females showed a strong and early preference for fat, which increased continuously with age. Differences between dietary groups in body fat mass were not observed with the exception of higher subcutaneous fat found in self-selecting rats. Moreover, insulinemia was lower in both male and female self-selecting rats. The high-protein, high-fat diet chosen by the self-selecting rats could be linked to a prevention of the age-related insulin resistance.

Here, in the follow-up from the same group, protein intake was circadian and high intakes are mentioned:

Rats that are allowed to select their diets [dietary self- selection (DSS)²] are able to regulate their daily energy intake, body weight gain, and reproductive cycle (1–4). Broad variations in macronutrient selection nonetheless occur. In the case of protein, the intake required to maintain a stable nitrogen balance and protein turnover in human adults and rats has been established at 10–15% of total energy, and a high protein intake is often considered an unnecessary burden, particularly for the liver and kidneys (5–7) With DSS, rats spontaneously ingest up to 30% or even 50% of their total energy intake in the form of protein.
(I know you'll be wanting references 5-7 from that study, well two are just "WHO Guidelines" and "Dietary Recommendations" type committee-generated rubbish, the only scientific evidence is here, and the abstract doesn't include morbidity or mortality data. Human data is that restricting animal protein is unnecessary and perhaps ill-advised in diabetic kidney disease, and that some hunter-gatherer diets, such as that of the Australian Aborigine, can be very high in protein - 50% or more - see the Drs Eades' Protein Power, p. 46-48)

The problem with rat experiments is that rats are never offered much in the way of real foods. It's always a choice between one type of supplemented junk and another with them. If they're lucky they'll get a little bacon or butter, but humane experiments like that are very much the exception.

Are there experiments testing Dietary Instinct in humans? Luckily, a similar experiment was run in a Chicago orphanage during the 1920s by Dr Clara M. Davis.

"Yes, Oliver, Dr Clara says you can have whatever you like!"

It is discussed here by Canadian science journalist Stephen Strauss:

' The foods she offered the children were varied, but all were generally thought to be healthy. Their intrinsic goodness meant that it would have been difficult for her small charges to veer too far from the nutritional straight-and-narrow.

[the list of foods:
1. Water
2. sweet milk (i.e. milk)
3. sour milk
4. sea salt
5. apples
6. bananas
7. orange juice
8. fresh pineapple
9. peaches
10. tomatoes
11. beets
12. carrots
13. peas
14. turnips
15. cauliflower
16. cabbage
17. spinach
18. potatoes
19. lettuce
20. oatmeal
21. wheat
22. cornmeal
23. barley
24. Ry-Krisp
25. beef
26. lamb
27. bone marrow
28. bone jelly
29. chicken
30. sweetbreads
31. brain
32. liver
33. kidneys
34. fish (haddock)
(some meat and offal was available both cooked and raw, where hygiene permitted, all cereals were boiled, no composite foods such as bread, soup or custard were offered. A wholefood is also a food by itself.)

“Errors the children's appetites must have made — they are inherent in any trial-and-error method — but the errors with such a food list were too trivial and too easily compensated for to be of importance or even to be detected.” The key thing was to provide healthy food and let children eat as much or as little of it as they wanted.

“The results of the experiment, then: Leave the selection of the foods to be made available to young children in the hands of their elders, where everyone has always known it belongs,” she told her peers in Montréal.

While an interesting double-hinged interpretation of her results, it was, Davis recognized, more a comforting argument than a true demonstration of the limitations of baby body wisdom. She did not present her little ones with a foolproof diet, just a not-intrinsically-foolish one.

It is actually beyond easy to imagine how Davis's orphans could have eaten themselves sick with healthy foods. Had one or more chosen only meat, fish and eggs, within short order they would likely have come down with scurvy. Had another been a fanatical vegan and eaten only fruits and vegetables, there is a good likelihood that he or she would have experienced a vitamin B12 deficiency and megaloblastic anemia.

Thus, the issue, really, was the extent to which an inner nutrition-seeking mechanism might lead children through the maze of choices they actually would face in the modern, eating world. What would happen, for example, if you offered the children not the Paleolithic diet of the Davis orphanage, but one where today's processed foodstuffs — think of a Big Mac mush, a slurry of Snickers and cola galore — were also on the menu?

Davis considered this and was not sure — particularly when confronted with the baroque ways her children constructed individual healthy diets out of a plethora of nutritious foods. To resolve the question, she told her Montréal audience she had decided to conduct just such a processed-food versus natural-food experiment. But alas, it was not to be: “The depression dashed this hope,” she laconically remarked, after a lack of funding forced the original experiment itself to end in 1931.

The PDF of Clara M. Davis's original report of her remarkable n=15 experiment can be seen here.
Average macronutrient disribution chosen was 17% protein, 35% fat, 48% carbohydrate (it would be hard to get a higher fat/protein ratio from the foods available, as there is no butter or oil).
The diet is both nutrient-dense and energy dense, in modern parlance. It is low in PUFA but fructose from fruit is readily available. We can only speculate on the reasons why pork was not included, whether this was a religious convenience or a health based decision.

There is an interesting reference in the paper to a form of dietary self-selection also being used in the Children's Memorial Hospital at that time. Children convalescing from the glandular fever epidemic consumed more carrots, beets, and raw beef. I'm guessing that raw beef and raw offal was not on the menu at the Children's Memorial Hospital, but who knows? In the context of Chicago and Prohibition, all bets are off.

The children were as healthy as 1920's children could be. I wonder if any have written memoirs, and I dearly hope Stephen Strauss completes his promised book on this affair. I know a lot of people who will be interested in that.

So there we have it - cut out sugar, stock the home with real foods only, and watch the appetite go feral.

Some Clara M. Davis from the interweb:
A letter to Clara M. Davis
A 1987 review (paywall)
A good blogger's take, from a baby-led weaning advocate.

Dr Clara M. Davis

A contemporary pop song summed up the healthy 1920's diet:

Everyone knows (I hope, because if they do it will save me a lot of time explaining) that inflammation can cause depression by activating the enzymes that degrade tryptophan, thus depleting the brain of serotonin.
Basically, macrophages hoover up tryptophan and pass it through Indoleamine 2,3,-Dioxygenase (IDO), where it is broken down. This is the pathway for the synthesis of niacin and nicotinamide, which is used to make NAD+.

(Note the other product, picolinic acid, thought to assist in absorption of minerals chromium and zinc)

There is the "sickness behaviour" explanation, whereby this response to infection, by making us less active, assists recovery, and the "sequestering" explanation whereby the macrophages act to deny tryptophan to pathogens, so that they don't have the advantage of extra NAD+. However, inflammation has many forms, and neither of these explain the response to chronic inflammation, when more activity and nicotinamide supplements are usually beneficial (nicotinamide seems to help in fighting infections too).

Supposing you are in the state known as reductive stress (not enough NAD+, too much NADH). This is associated with metabolic inflexibility, metabolic syndrome, and so on.
Reductive stress is mentioned by Peter D in this post. It is associated with fatty liver (steatosis) of chronic Hep C infection here, in these words:

the impairment of NADH oxidation to NAD, with consequent NADH accumulation, is a characteristic figure of mitochondrial dysfunction occurring in fatty liver due to high fat diet (HFD) in rats*.
So, how can NADH be converted back to NAD+ in these states? If lactate is available, metabolising this will restore NAD+, if ketone bodies are available, ditto for their interconversion (so exercise or carbohydrate restriction/fasting are protective against reductive stress). Electrophilic methyl groups in the diet - choline, carnitine, SAMe - may accept the H+ from NADH to form methane, which is dissipated.
But electrophilic methyl groups are hard to come by in the type of diets that cause reductive stress. No choline in flour, sugar, or vegetable oil. (Brilliant analysis of why this matters by Paul Jaminet here, also explaining that "high fat diet (HFD) in rats" line above*).

Also, fresh NAD+ can be supplied from outside the cell. From B3 if you're supplementing or eating good food (in which case your cells shouldn't have easily got into a reductive stress state, but requirements for B3 are unusually high for a co-enzyme vitamin). Or, if you're in the fasting state or your dietary B3 is inadequate, from tryptophan via IDO (Tryptophan 2,3-Dioxygenase is the hepatic equivalent). Which inflammation will upregulate.

So the hypothesis is, that reductive stress is an emergency (perhaps mimicking pellagra) that warrants an inflammatory response if this is what it takes to supply extra NAD+. But this process can not only deplete tryptophan and serotonin, but also produce a number of intermediate compounds that can are potentially neurotoxic.

The concentration of potentially neurotoxic compounds, such as 3OH-kynurenine, 3-OH-anthranilic acid, and quinolinic acid (QUIN) that are formed along the metabolic pathway leading from tryptophan to NAD (the kynurenine pathway) significantly increases in blood and cerebrospinal fluid of patients affected by a number of inflammatory neurological disorders and in animal models of immune activation.
So what is the messenger that reductive stress state cells produce, which triggers IDO in macrophages?
Why not the extra superoxide that is produced? This potentiates NF-kappaB,

Under normoxic conditions, NFκB is bound to one of several inhibitory proteins (e.g., IκB) that prevent its nuclear translocation. Hyperoxia or elevations of ROS cause the ubiquination and destruction of the inhibitory proteins, freeing NFκB and allowing it to bind to target gene promoters.

These target genes include INF-gamma and TNF-alpha. INF-gamma drives IDO in macrophages.
Nicotinamide is an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1) that, through enhancement of nuclear kappa B-mediated transcription, plays a pivotal role in the expression of inflammatory cytokines, chemokines, adhesion molecules, and inflammatory mediators. Through interaction with CD38 and inhibition of IL-1, IL-12, and TNF-α production, nicotinamide produces a mild TH2 bias.

(in other words, the product of the inflammatory cascade that begins with reductive stress will inhibit it.)
So this may be part of a homeostatic survival mechanism in B3 deficiency (pellagra), which reductive stress imitates. In which case inflammation and depression is secondary to metabolic disregulation in diet-and-lifestyle related diseases. It is, so to speak, a perfectly natural, adaptive consequence of eating the wrong things and forgetting to exercise.

Edit: Aubrey de Grey's mitochondrial theory of ageing describes a mechanism by which surplus electrons from cytosolic NADH can be exported from the cell, recycling NAD+, via the plasma membrane redox system (pdf). Jettisoned into intercellular space, the electrons combine with O2 to form the superoxide reducing radical; reduction of transition metals (ferretin, ceruloplasmin) by superoxide also creates conditions for generation of oxidising radicals such as hydroxyl and peroxide. (note that RBCs lack the ability that other cells have to transfer electrons to O2 and form superoxide; RBC PMRS is an antioxidant system, other cell-types' PMRS are more likely to produce pro-oxidant effects)
In both that paper and this one, by two different sets of authors, there is a role in the PMRS for ascorbic acid (AA) and its oxidised
form dehydroascorbic acid (DHA is the product of 2-electron oxidation, the 1-electron product of AA is a free radical that becomes more common in the senescent leaves of plants pdf.)

The authors hypothesize that the increased PMRS in erythrocytes during aging may be a protective mechanism of the system for efficient extracellular DHA reduction and ascorbate recycling under condition of increased oxidative stress.

And, perhaps, increased cycling of ascorbate is also a response to reductive stress. Oxidative stress, when not adaptive, as in the immune response, or toxic in nature, is the product of reductive stress, and both are increased by hypercaloric intakes of micronutrient deficient diets.

Aspirin (acetylsalicyclic acid) is one of those drugs that blurs the distinction between the natural world and the products of human ingenuity, being a barely-tweaked analogue of salicylic acid. Salicylic acid is not only prevalent in the diet, it appears to be synthesised endogenously in fasting states.
(music: Seven Fishes by Jigsaw)

Aspirin has long been regarded ambivalently in medicine. On the one hand it kills pain and reduces fever, on the other hand excess can make the gut bleed and damage the kidneys, and even cause hepatitis. Low-dose, buffered aspirin is commonly used as a preventive of heart attacks and strokes, but its overall effectiveness in this role is questioned:

Meta-Analysis of Multiple Primary Prevention Trials of Cardiovascular Events Using Aspirin

The meta-analysis suggested superiority of aspirin for total CV events and nonfatal MI, with nonsignificant results for decreased risk for stroke, CV mortality, and all-cause mortality. There was no evidence of a statistical bias. In conclusion, aspirin decreased the risk for CV events and nonfatal MI in this large sample. Thus, primary prevention with aspirin decreased the risk for total CV events and nonfatal MI, but there were no significant differences in the incidences of stroke, CV mortality, all-cause mortality and total coronary heart disease.

So the findings in this survey were unexpected:

Nonsteroidal Anti-inflammatory Drug Use, Chronic Liver Disease, and Hepatocellular Carcinoma

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce chronic inflammation and risk of many cancers, but their effect on risk of hepatocellular carcinoma (HCC) and death due to chronic liver disease (CLD) has not been investigated.

Methods We analyzed prospective data on 300504 men and women aged 50 to 71 years in the National Institutes of Health–AARP Diet and Health Study cohort and linked self-reported aspirin and nonaspirin NSAID use with registry-confirmed diagnoses of HCC (n=250) and death due to CLD (n=428, excluding HCC). We calculated hazard rate ratios (RRs) and their two-sided 95% confidence intervals (CIs) using Cox proportional hazard regression models with adjustment for age, sex, race/ethnicity, cigarette smoking, alcohol consumption, diabetes, and body mass index. All tests of statistical significance were two-sided.

Results Aspirin users had statistically significant reduced risks of incidence of HCC (RR = 0.59; 95% CI = 0.45 to 0.77) and mortality due to CLD (RR = 0.55; 95% CI = 0.45 to 0.67) compared to those who did not use aspirin. In contrast, users of nonaspirin NSAIDs had a reduced risk of mortality due to CLD (RR = 0.74; 95% CI= 0.61 to 0.90) but did not have lower risk of incidence of HCC (RR = 1.08; 95% CI = 0.84 to 1.39) compared to those who did not use nonaspirin NSAIDs. The risk estimates did not vary in statistical significance by frequency (monthly, weekly, daily) of aspirin use, but the reduced risk of mortality due to CLD was statistically significant only among monthly users of nonaspirin NSAIDs compared to non-users.

Conclusions Aspirin use was associated with reduced risk of developing HCC and of death due to CLD whereas nonaspirin NSAID use was only associated with reduced risk of death due to CLD.

Now, these are huge correlations, especially when you consider that the use of NSAIDs is considered to put one at risk of leaky gut syndromes, and that SIBO and endotoxaemia are proving to be significant factors in the development of chronic liver disease. When epidemiology goes so strongly against the grain of one's expectations, one really should sit up and take notice. There's an extra convincing feature here - the differential correlations of aspirin (less CLD, less HCC) and other NSAIDs (less CLD but no reduction in cancers). If the result was co-incidental (people with better liver function more able to use NSAIDs, for instance) this difference shouldn't exist. Non-aspirin NSAIDs lumped together by the methodology include (are mainly) ibuprofen and paracetamol (acetaminophen) and the latter can cause liver damage by depleting reduced glutathione. This has cancelled out the anti-cancer benefit (we might hypothesise) but the aspirin-like anti-inflammatory effects of ibuprofen still show.

Of course if you already have low platelets and poor blood clotting due to cirrhosis it might be a bit late to take any advantage you might see in this research. However, there is an alternative theory; that Aspirin should be considered as a salicylate supplement, and that fruits and vegetables, which are naturally rich in salicylate, can supply the same benefit. Wiki lists the sources thus:
Unripe fruits and vegetables are natural sources of salicylic acid, particularly blackberries, blueberries, cantaloupes, dates, raisins, kiwi fruits, guavas, apricots, green pepper, olives, tomatoes, radish and chicory; also mushrooms. Some herbs and spices contain quite high amounts, although meat, poultry, fish, eggs and dairy products all have little to no salicylates. Of the legumes, seeds, nuts, and cereals, only almonds, water chestnuts and peanuts have significant amounts.

Almonds just got interesting again...

Some people are intolerant of salicylates. These people may have little need for aspirin anyway if blood salicylate levels are naturally high. Removing 75% of salicylate from the body involves conjugation with glycine (requiring pantothenic acid - vitamin B5 - plus sulfur, as acetyl CoA), and clearance of salicylate might improve on a paleo diet with bone broth to supply glycine, and low carbohydrate intakes to stimulate trans-sulfation and acetyl-CoA synthesis.

Anyway the take home message from the Aspirin study as I see it - if you're concerned about the health of your liver, and your platelets are still in the normal range, you needn't be afraid to use aspirin. Though it might be a good idea to also ensure you're getting enough vitamin K.

Ginkgo Biloba Extract and Cancer

It's a common enough fallacy that natural medicines, especially ones in common use, can't be as harmful as pharmaceuticals. The appeal to nature, the appeal to antiquity, and all that. The fact is that the supplement industry is very poorly regulated in most countries, and no-one has yet worked out how to regulate it in a way that consumers, long used to experimenting freely with often cheap and sometimes effective natural medicines, will tolerate. It doesn't help that regulation is usually the business of government agencies that are seen, with some reason, as being in the pocket of Big Pharma. A few weeks ago Stephan Guyenet tweeted about this study (PDF) which shows commercial ginkgo extract is highly carcinogenic in rats and mice.

Liver: The incidences of multiple hepatocellular

adenoma, hepatocellular carcinoma, and hepatoblastoma

were increased in all dosed groups of males; multiple

hepatocellular adenoma incidences were increased in all

dosed groups of females, and multiple hepatocellular

carcinoma and hepatoblastoma incidences were

increased in 600 and 2,000 mg/kg females. When single and multiple neoplasm

incidences were combined, significant increases were

seen in the incidences of hepatocellular adenoma in

200 mg/kg males and all dosed groups of females,

hepatocellular carcinoma in all dosed groups of males

and 2,000 mg/kg females, and hepatoblastoma in all

dosed groups of males and 600 and 2,000 mg/kg

females. These significantly

increased incidences also exceeded the historical control

ranges for these neoplasms from corn oil gavage studies

and all routes of administration (except for hepatocellular adenoma in 200 mg/kg females)

(Cancers were also found to be significantly increased at a number of other sites including the nose and thyroid).

One could take this with a grain of salt, rats being rats, and the doses being a little higher than human doses, but the paper does refer to human trials, and these results too give cause for concern.

Humans

Two epidemiological studies explored carcinogenicity

associated with use of Ginkgo biloba supplements. In a

population-based, case-control study reported by Ye

et al. (2007), in which the case group included 668

women in Massachusetts and New Hampshire

diagnosed with epithelial ovarian cancer matched to

721 women in the control group, an inverse association

(OR=0.41; 95% confidence interval, 0.20-0.84; P=0.01)

was found between Ginkgo biloba use and risk for

ovarian cancer. A more recent study by Biggs et al.

(2010) used data from the largest epidemiological study

of Ginkgo biloba efficacy (Ginkgo Evaluation of

Memory Study) conducted to date to analyze cancer as a

secondary endpoint. The study population consisted of

3,069 participants, age 75 years or greater, that were

randomly assigned to receive twice daily doses of either

a placebo or Ginkgo biloba extract (120 mg EGb 761®)

and were followed for approximately 6 years.

Researchers found an increased risk of breast (hazard

ratio, 2.15; 95% confidence interval, 0.97-4.80; P=0.06)

and colorectal (hazard ratio, 1.62; 95% confidence

interval, 0.92-2.87; P=0.10) cancers and a decreased

risk of prostate cancer (hazard ratio, 0.71;

95% confidence interval, 0.43-1.17; P=0.18) in the

population receiving Ginkgo biloba extract.

It seems to me that a more than doubled incidence of breast cancer in a randomized controlled study is the kind of result that should have been more widely discussed than it was. If this happened in a study of statins or aspartame, the whole internet would be abuzz with it. Why does Ginkgo get a pass?

Ginkgo Biloba leaf extract is not a traditional Chinese medicine. There is some mention of monks at some time making tea of the leaves, but they do not appear in any TCM formulary that I have perused. The seeds appear occasionally but are recognized as toxic and their use is rare. Ginkgo leaf extract contains many worthwhile compounds (I could fill another post with these), and it's the best treatment I know to give someone who has memory impairment from chronic marijuana use. It has a potent antifibrotic effect and has been used in modern Chinese hepatitis therapies. It will inhibit many cancers in vitro (the difference can be small between what might cause cancers, and what might treat them; some chemo drugs, as well as radiation, are carcinogenic). I used to take Ginkgo regularly every now and then. I'll still take it when I have to drive long distances, on the principle that the increased alertness will reduce risk in the short term without exposing me to longer term risk.
Ginkgo is a mixture of many different types of phytochemical, and some might be more effective once isolated. It seems likely that the carcinogenic component will be identified and removed from extracts, hopefully sooner than later. The uncritical acceptance of the idea that whole herbal extracts are intrinsically more effective and safer than isolated compounds may have been mistaken in the case of Ginkgo.

Well, here we have a drug that might be better for us than was previously thought, and a popular herbal product that might actually be harmful in its present form.

What is the world coming to?

As a general rule, I think it's safe to assume that cheap energy foods are driving the obesity epidemic.
I'm talking about sugar in drinks and lollies, flour in pasta and noodles and bread (one only has to include potatoes, normally a respectable enough vegetable, after deep frying and other extreme processing) and cheap oils. And the mixture of all 3 in biscuits, pastries, cakes, and "treats".

These are the foods the consumption of which has increased during the obesity epidemic. WHO reports that consumption of animal fats has decreased, but total fat consumption has increased. Where intake of calories has increased, these are the foods supplying the extra.

To give only one example, this paper (Behavioral risk factors for obesity during health transition in Vanuatu, South Pacific) found that

"Both the nutrient content and the preparation methods of tinned fish likely contribute to its association with obesity. Tinned fish canned in oil or sauce has higher fat content than most types of fresh fish (21). Furthermore, based on our observations, tinned fish and meat are often served with instant noodles and rice, whereas fresh fish and meat more often accompany dishes made with traditional root crops and vegetables, which are less calorie-dense by comparison. A heavy reliance on tinned fish in urban areas was noted during the first known nutrition survey conducted in Vanuatu in 1951 (22), and has been observed in many areas of the Pacific (23–25).

Our findings are similar to those of the Vanuatu Ministry of Health 1998 NCD survey, which highlighted associations among obesity and daily consumption of nontraditional fat sources (OR=2.19), including oil, margarine/butter, milk, fresh meat, poultry, tinned meat, and tinned fish (11). However, our analyses suggest that tinned fish might contribute more to the risk of nontraditional fats compared to fresh meat (including poultry). In fact, including fresh meat in the nontraditional fats category might actually weaken the observed association, since this emerged as a protective factor in linear regression models, perhaps because fresh meat displaces other less healthy options in the diet."

Tinned fish eaten in the Pacific is canned in soy oil. This, as well as the fact of it being eaten with instant noodles or rice, cancels out the antiobesigenic effects of fish oil omega 3 fatty acids (and, indeed, of protein) in the manner described in this review (Of Mice and Men; Factors abrogating the antiobesity effect of Omega-3 fatty acids).

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In the USA, consumption of omega 3 has remained low, but that of omega 6 has climbed

Now it may be that butter is fattening, but this does not mean that it drives obesity (to do this a food has to not only supply energy, it also has to promote fat storage and overeating; there are particular hormonal pathways for this and every fat or carbohydrate or combination of the two doesn't influence these pathways to the same extent or even in the same direction - see the Of Mice and Men paper again - here is where a calorie is not a calorie). But let's assume, for avoiding arguments' sake, evidence to the contrary notwithstanding, that butter and soy oil are equally fattening at 9 calories per gram.
500 grams of butter, in New Zealand costs $4-5.
At $8.49 for 2 litres, soy oil is half that price per calorie.
Extra virgin olive oil, which everyone thinks is healthy, is $11.99 a litre, only a little more expensive than butter. Still cheap for 9,000 calories.
The idea of a minimum price, rather than a tax, is twofold; people might choose to use less fat because the cheapest fats would cost more. But the fats that are nutritious (butter is an important source of fat-soluble vitamins) or healthful (olive oil is thought to contain beneficial antioxidants) would not be affected, if their price were to be used as the benchmark for a minimum price for all fats.

How would this apply to sugars?
White sugar costs $1.91 for 500g (it gets complicated here because sugar becomes much cheaper in bulk, more nutritious sweeteners not so much.
Honey (the cheap clover variety) costs $5.19 for 500g. If that's too high a price for sugar, let's look at the least refined form of sugar - treacle. At $6.75 per Kg (price from cache), more than sugar (especially bulk sugar) but still cheap for 4,000 calories.

(Note: I am using prices from the Countdown website because they are available and internally consistent. I shop at Pak'nSave in Auckland so I'm used to prices being a bit lower. The examples I've used here are just that - examples).

From here on in, it's a job for experts. Foods have different prices per calorie at different sizes. It's relatively easy doing this with pure fats and sugars, it will be harder for me to calculate, say, for noodles vs potatoes without knowing the carbohydrate %. (I'm not an economist, I'm not even a shop assistant.)
But here we have white bread - only $1.48 for 600g.
And here's wholemeal bread, at $3.99 for 750g, about twice the price. Not much of a comparison here as the wholemeal bread is likely more processed than the white bread (read the label people, apparently it is no longer possible to bake bread without adding soy protein and a bunch of other non-traditional additives), but still, Government think it's healthier, and maybe it still is, and Government will be the ones responsible for administering any antiobesity food pricing system or tax.
And I'd rather they altered the food environment by pricing up the cheap, empty calories to be closer in price to the more nourishing ones, as opposed to taxing all fats (which would increase the cost of butter or olive oil more than that of soy or corn oil, because they cost more to start with), or taxing saturated fat, which would miss out gutter oils and cheap calories altogether. Similarly, taxing sugars would increase the price of honey or molasses more than that of white sugar or HFCS.

And yes, I know all the arguments as to why honey is so little different from sugar/HCFS as to make no difference. Those arguments apply if you think fructose is uniquely toxic, or if you're treating a condition for which carbohydrate needs to be restricted. But in the context of this discussion, how many people do you know who became obese eating honey without eating other junk carbohydrates? Honey has a flavour which tends to prevent it being overused in cooking in quite the same blithe way that sugar can be. And, low vitamin content and mere traces of minerals notwithstanding, it's a complete food for many of the bees in a hive. And it's well Paleo too, hunter-gatherers lap it up. Any regime of food pricing for health has to be about Lesser Evils, not Perfect Diets.

Based on these examples, we might come up with a minimum price of 0.1c per calorie (Kcal of course, food calories are always Kcal in physical terminology). This would give us a minimum price of $9.00 for a litre of soy or olive oil, $4.50 for 500g of butter, $4.00 for 1kg of sugar or honey. This conveniently rounded, decimal rate is almost perfect for these foods at present prices, and works across fat and sugar.

However, a Big Mac, at 492 calories, would have a minimum price of 49c. It has the more expensive protein in it, and the cost of extra labour and overheads, so it already costs more than that. Large fries would have about the same minimum price as a Big Mac, but are cheaper than Big Macs in reality (no meat, fries are just starch and oil). Processed fast food would need a higher rate, if you did want to target those calories. I'm not singling out McDonalds for effect; a KFC menu gives much the same result. But this does show targeting junk food won't catch the cheapest and emptiest calories, just some of the foods most likely to be addictive. And a change of price at the supermarket is a way of educating people about the quality of their food, which may carry over into the fast food environment. And far and away, calories consumed at home still outweigh those eaten at fast food joints.

So, back to the drawing board? I've taxed the limits of my rudimentary comprehension here. My brain hurts already. No more sums for me, but feel free to add your own.

Postscript; minimum pricing for one source of empty calories, alcohol, is already under investigation.

Much of the logic behind this initiative is similar to the the arguments I've raised.

Let’s say the rate was set at $1.20. A 750 ml bottle of wine with 13 percent alcohol content has 7.7 standard drinks so could not be sold for less than $9.24. Not really much of a change there. However, a 3-litre cask of wine with 12.5 percent alcohol content contains 30 standard drinks so could not be sold for less than $36 – more than twice the current retail price.

And the drawbacks listed at the end of the article also apply to minimum pricing on food.

However, minimum pricing is not a magic bullet and is likely to have different effects on different populations. New Zealand is likely to be far more successful in reducing the use and misuse of alcohol across the spectrum if minimum pricing is introduced alongside a wider suite of policies.

For starters, without the recommended increase in the excise tax on alcohol or other similar measures, the additional revenue gathered under minimum pricing goes to the alcohol producers. In Canada, the state is the retailer, so this is not an issue. However, in New Zealand, this would be a lost opportunity for government, where even a small price increase is likely to result in significant additional revenue. That revenue would go a long way towards funding other harm-reduction activities, such as treatment, prevention or education. Perversely, if left in the coffers of the alcohol industry, it could be spent on measures designed to increase alcohol consumption (for example through increased expenditure on marketing).

Magnus Pyke was the protégé of Jack Drummond, the British nutritionist who largely directed food policy for Britain's war effort during the Second World War. Wiki states:

On 1 February 1940, he was appointed Scientific Adviser to the Ministry of Food. When Lord Woolton became Minister of Food in April 1940, Drummond produced a plan for the distribution of food based on "sound nutritional principles". He recognised that rationing was the perfect opportunity to attack what he called "dietetic ignorance" and that, if successful, he would be able not just to maintain but to improve the nation's health.

Thanks to Drummond's advice, the effect of rationing was to introduce more protein and vitamins to the diet of the poorest in society, while the better off were obliged to cut their consumption of meat, fats, sugar, and eggs. Follow-up studies after the war showed that, despite rationing and the stresses of war, the population's health had improved.

This is misleading; egg consumption was only cut because Britain's eggs (and bacon) were imported from Denmark. And people were encouraged to use meat drippings in place of butter, and use offals in place of meat, both of which were rationed, so it is unlikely fat intake as % of energy fell much (that the well-off were forced to reduce their total calorie intake across the board accounts for the lavish descriptions of meals in the books Evelyn Waugh wrote during the war, Put Out More Flags and Brideshead Revisisted).
An important contribution to the health benefits of rationing was, that the amount of wheat available for consumption by humans decreased, and people were encouraged to eat potatoes instead. More wheat (which was imported from the US and Canada) was fed to cattle for milk production (which was increased), and wheat for bread was milled at a lower extraction rate (less refined) to include more vitamins - a controversial policy as this also decreased its digestibility - and, supplemental B vitamins and calcium were also added to flour, for the first time in the UK. The story is summarised well in a chapter of the book Britain's War Machine.
Front Cover

Jack Drummond was famously murdered with his family in France after the war (a crime which has generated its own conspiracy theory industry among the French), and Magnus Pyke took his place as the don of Nutrition. Success in Nutrition is a 'studybook' (all the information needed to pass all the nutrition examinations of the day) he wrote in 1975, and is as excellent a nutrition text as anyone could wish for. There is a little nod to the lipid hypothesis, but it hasn't skewed the business of getting people properly fed yet - it's a work worthy of Drummond (to whom it is dedicated).
Magnus Pyke O.B.E., Ph.D., C.Chem, F.R.S.C., F.I.Biol., F.I.F.S.T., F.R.S.E. also, incredibly, according to Wiki, wrote the book 'Tricky and Portishead and Other Stonehead Bristol Sounds of the Future'. He makes an appearance (shouting "Science!") in this pop video, so that might even be true.

Anyway, I wanted to quote some words of wisdom from Success in Nutrition, from the chapter on Energy Intake: After warning that BMI does not give an accurate indication of health for everyone, and that variations in BMR render it extremely difficult to specify the right caloric intake for any individual, Professor Pyke concludes;
The most direct way of finding out whether an individual's energy intake is nutritionally adequate is to ask him whether he has enough to eat. If he says 'yes' and if his body weight is satisfactory, his energy intake is satisfactory too.

After discussing (i) different types of bodies, the next section covers
(ii) The influence of social ideas on the ideal body weight.

The purpose of good nutrition is health and health, let us repeat, can be defined as 'complete, physical, mental and social well-being and not merely the absence of ill-health and infirmity'. Different communities have different ideas about what they consider to be the appropriate body weight desirable for complete social well-being.
Although, as we shall explain later, there are certain technical methods for measuring obesity, which is a sign of malnutrition, there is a margin within which people can choose what kind of people they would like to be. A community which thinks a great deal (perhaps in fact too much) about health and nutrition and how its members look, who like their children to be big and their young men and women plump and buxom, may accept certain body weights as standards of optimum nutrition. In another community with a different idea of 'complete social well-being', where people consider that children should work, young men and women overcome strict tests before being accepted as full members of society, and adults think little of their appearance and more of some duty or purpose, considerably lower body weight may be accepted as normal. Yet, though it is difficult for a nutritionist to judge, both may be equally healthy although the members of one community may obtain more units of energy in their diet than those of the other.

- "it is difficult for a nutritionist to judge". Not words we've been hearing much in recent decades, which might be an example of the Dunning-Kruger effect in action.And very interesting that the ideal of a plump, buxom society should be the example chosen as recently as 1975. No-one, however eccentric, would choose that example today. Few nutritionists seem to be aware of the possibility of the existence of a healthy, plump, buxom society; they are more likely to be propagandists for "some duty or purpose", whether it be slimness, the hope of longevity, increased muscular development, or self-sacrificial attempts at saving the planet. In other words, a society's valuing "some duty or purpose" now includes it thinking "a great deal (perhaps in fact too much) about health and nutrition and how its members look".
A good addition to any library of classic nutrition texts, and one that makes me curious to read Pyke's other works, such as Synthetic Food, listed on the Wikipedia page. That book about Tricky and Portishead and the Stonehead Sounds of Bristol doesn't seem to be on Google, unfortunately.

Some time ago I came across this interesting paper

Because it seemed to beg the important question of linoleate intake, while addressing both fructose intake and insulin resistance, I took the (for me) relatively unusual step of contacting the corresponding author. I never received a response, but because my email summarised my view of the role of linoleate in chronic Hepatitis C infection (CHC) I have decided to reproduce it here.

Dear Dr Petta,

I am an independent Hepatitis C researcher looking at the relationship between HCV and diet, and I was interested by this paper which you authored.

There is much of interest in the paper and I just want to single out one aspect, typified by this line from a reference paper:
Low cholesterol (OR 0.988, 95%CI 0.975–0.999,P = 0.04) was independently linked to severe fibrosis, and high LDL was the only independent positive predictors of both RVR and SVR (OR 1.036; 95%CI 1.017–1.055; P < 0.001; and OR 1.016; 95%CI 1.001–1.031; P = 0.04 respectively).
Although these do not seem very large OR differentials (as presented in this example), the finding is often replicated (the ORs will vary depending how "high" and "low" LDL are defined).

Your paper cites one possible mechanism "These aspects have been related, on one hand, to a competition for LDL receptor sites which prevents viral entry into hepatocytes and thus to an increased exposure of HCV to the host serum immune response".

It seems to me that LDL-R numbers, given their role in HCV life cycle, are something that it would be worthwhile for people with CHC to mimimize, and that this is easily possible through diet.

I notice the correlation between fibrosis and fructose consumption, but I feel that if one looked for a correlation between linoleic acid intake and HCV pathology, this would be stronger. I am aware of one study where high polyunsaturated fat intake correlated with steatosis (OR 2.7), while saturated fat was neutral and MUFA was protective. This study did not distinguish between linoleate and other PUFA (ALA, EPA, DHA and arachidonic acid). I believe that if this distinction had been made, linoleate would have shown an even stronger correlation with pathology.

There are a number of reasons why this should be the case.

Firstly, increased expression of LDL-R increasing viral opportunity to infect HCV-naive cells.

Secondly, steatosis-promoting effect of linoleate. The animal model of NAFLD uses high-linoleate diets and fails to produce steatosis when fats such as butter or coconut oil are fed. NAFLD has become a much more common disease since high-linoleate oils have replaced tallow in deep frying, and linoleate-based spreads have replaced butter.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1805500/

Thirdly, the heating of polyunsaturated oils produces peroxides which directly promote liver inflammation.http://journal-of-hepatology.eu/article/PIIS0168827813002808/abstract

Fourthly, in animal models alcoholic liver disease can only be produced when high-PUFA oils or fats are added to the diet, and it is prevented when beef fat, coconut oil etc are fed concurrently with alcohol.http://download.journals.elsevierhealth.com/pdfs/journals/0016-5085/PII0016508595903542.pdf
Fifthly, linoleate increases both hepatic uptake of cholesterol and its synthesis, and high intakes result in elevations of hepatic free cholesterol and non-esterified fatty acids.

http://www.jlr.org/content/31/8/1413.full.pdf
http://suppversity.blogspot.co.nz/2013/08/high-fish-soy-lard-low-fat-diets-how-do.html

Because EPA, DHA and arachidonic acid all suppress HCV replication and can substitute for dietary linoleic acid in much smaller amounts, it is relatively easy to compose a nutritious diet which is low in linoleate. Many diets today are deliberately designed to minimize this problematic, and currently over-supplied, nutrient, especially diets of the "Paleo" type, such as the "Perfect Health Diet". These diets, which also minimize fructose and high-GI carbohydrates, are often higher in dietary cholesterol than might be considered optimal for someone with CHC, but this could easily be adjusted (or one could supplement with taurine).

My own health has improved since I stopped using rice bran oil and other cooking and salad oils and started cooking with dripping (tallow) and adding butter and olive oil as a seasoning.(*)

I write about these ideas on my blog, discussing a low-carb, paleo approach to Hep C: http://hopefulgeranium.blogspot.co.nz/

In any case, the point of this email is to raise the issue of linoleate from vegetable salad and cooking oils (and also pork and chicken fat) as a worthwhile nutrient to be considered in analysis of CHC and diet, and distinguished from other PUFAs such as omega 3 from plants and fish.

Thanking you,

George D. Henderson
Huia New Zealand
puddleg@gmail.com

(* one way in which my health improved after this switch was instructive; being on drugs at the time, I often used to burn myself on the stove, with blisters an inevitable consequence. After increasing saturation of dietary fats, any encounters with hot elements now result instead in patches of dead skin, which quickly clear, and not the classic deep blister.)

Since then, another link between linoleic acid and CHC has turned up; the role of cannabinoid receptors, the natural ligand for which is anandamide (an endogenous cannabinoid derived from omega 6 fatty acids).

The endocannabinoid system (ECS) includes cannabinoid (CB1 and CB2) receptors and their endogenous ligands (i.e., the endocannabinoids anandamide and 2-arachydonylglycerol) as well as proteins involved in endocannabinoids biosynthesis and degradation (). The ECS is present in the liver and undergoes adaptive changes in response to noxious stimuli. Endocannabinoids as well as CB1 and CB2 receptors (which are, respectively, either faintly or not expressed in normal livers) are up-regulated in experimental liver injury and liver cirrhosis of various etiologies. In vivo, CB1 receptor activation promotes fat accumulation, triggers inflammation in nonalcoholic and alcoholic fatty liver diseases, contributes to the progression of chronic hepatitis to cirrhosis by stimulating fibrogenesis, and is also implicated in hemodynamic and neurological consequences associated with liver cirrhosis, including portal hypertension, encephalopathy, and cardiomyopathy (–). Conversely, activation of CB2receptors exerts antifibrogenic and antiinflammatory effects in experimental models of liver disease (). These pharmacological effects make CB2 agonists and CB1 antagonists promising candidates for the treatment of fibrosis in chronic liver pathologies. By disclosing a prominent CB1-mediated role of anandamide in the early phase of liver regeneration, Mukhopadhyay et al. () provide additional and significant support to the prominent role of the ECS in liver biology in an article in PNAS.

This makes heavy (daily) pot smoking dangerous in presence of liver injury

Cannabinoids present in Cannabis sativa (marijuana) exert biological effects via cannabinoid receptors CB1 and CB2. We recently demonstrated that CB1 and CB2 receptors regulate progression of experimental liver fibrosis. We therefore investigated the impact of cannabis smoking on fibrosis progression rate in patients with chronic hepatitis C (CHC). Two hundred seventy consecutive untreated patients with CHC of known duration undergoing liver biopsy were studied. Demographic, epidemiological, metabolic, and virological data were recorded, and detailed histories of cannabis, alcohol, and tobacco use over the span of hepatitis C virus infection were obtained. Fibrosis stage, steatosis, and activity grades were scored according to Metavir system. Patients were categorized as noncannabis users (52.2%), occasional users (14.8%), or daily users (33.0%), and the relationship between cannabis use and fibrosis progression rate (FPR) or fibrosis stage was assessed. On multivariate analysis, six factors were independently related to a FPR greater than 0.074 (median value of the cohort): daily cannabis use (OR = 3.4 [1.5-7.4]), Metavir activity grade A2 or higher (OR = 5.4 [2.9-10.3]), age at contamination of more than 40 years (OR = 10.5 [3.0-37.1]), genotype 3 (OR = 3.4 [1.5-7.7]), excessive alcohol intake (OR = 2.2 [1.1-4.5]), and steatosis (OR = 2.0 [1.0-4.1]). Daily cannabis use was also an independent predictor of a rapid FPR (>0.15) (OR = 3.6 [1.5-7.5]). Finally, severe fibrosis (≥F3) was also predicted by daily cannabis use (OR = 2.5 [1.1-5.6]; P = .034), independently of Metavir activity grade, excessive alcohol intake, age at liver biopsy, steatosis, and tobacco smoking. In conclusion, daily cannabis smoking is significantly associated with fibrosis progression during CHC. Patients with ongoing CHC should be advised to refrain from regular cannabis use. (Hepatology 2005;.)
Though some studies disagree:Conclusions In this prospective analysis we found no evidence for an association between marijuana smoking and significant liver fibrosis progression in HIV/HCV coinfection. A slight increase in the hazard of cirrhosis and ESLD with higher intensity of marijuana smoking was attenuated after lagging marijuana exposure, suggesting that reverse causation due to self-medication could explain previous results.

Naturally occuring delta-9 THC is a weak agonist ligand of the cannabinoid receptors, thus can exert both agonist and antagonist effects depending on what other ligands are present. This is why it is non-toxic compared to most synthetic cannabinoids, which are designed as strong agonist ligands.

To cut a long story short, Dietary Linoleic Acid Elevates Endogenous 2-AG and Anandamide and Induces Obesity. Or, if one has chronic Hep C, steatosis. As in this paper (the one I mentioned above in the email, with the 2.7 OR between high polyunsaturated fat intake and steatosis - the methodology leaves a lot to be desired, but the the differential between the correlations of the 3 different fat types impresses me).

BTW, CB1 receptor is only strongly expressed, or expressed at all, in injured liver. So it's very unlikely that cannabis causes problems in people without a pre-existing liver condition like Hep C. Synthetic cannabinoids can however cause kidney failure. Which is probably a worse outcome than a little scarring of the liver.
Nothing demonstrates the lack of legitimacy behind cannabis prohibition as much as the trade in synthetic cannabinoids. But then, consider where sugar sweetened beverages (sodas) came from originally; as "soft drinks", SSBs were developed by temperance advocates as an alternative to hard liquor. The law of unintended consequences is a bitch.

For additional information about linoleic acid's cancer and obesity-promoting effects, this post is a good place to start, and this one has some interesting further data. In fact, there are papers relating to linoleic acid and liver health scattered throughout this blog and I find the search engine pretty useful for recovering them.

Late last year, after my usual visit to the Hepatology Department at Auckland Hospital (actually it has the encouraging name Liver Transplant Unit, but I choose to ignore that) I received a call asking me if I'd be interested in taking part in a drug trial. I've had Hep C, genotype 3, for a long time, and I've never fancied taking antivirals. When I was first diagnosed in 1991, interferon monotherapy was a terrible thing. Most people who did it suffered greatly, very few cleared the virus (only one guy I know, and he was the only one who didn't suffer at all), and most of those who didn't clear the virus have died of liver cancer since or needed liver transplants. Later on they added Ribavirin to the Interferon, people got a bit sicker but more of them cleared. But still, those who didn't clear weren't better off fr having tried. At this point I felt so sick that I couldn't have borne feeling any worse for the 6 months or a year or whatever the treatment took, and the odds didn't seem that good. Later, when I started taking antioxidants, fixing my diet, and feeling much better, I thought "hey, I'm getting things done, feeling good - why risk screwing all that up?". I learned I could control my viral load and keep my liver fat-free by restricting carbs, and that I could get rid of most of the symptoms by eating Paleo, without any longer spending a fortune on supplements.
But over the last year or so I met a few people who'd been in trials of some new drugs. They hadn't needed to take Interferon, they'd cleared the virus, and they couldn't tell me anything bad about the treatment. That sounded promising. I've always thought that "fighting the dragon" was a foolish idea. HCV has some immunosuppressive effects that protect the liver, together with the virus, from the host immune response to some extent. You don't necessarily want to lift that protection without good reason. The virus is still cytotoxic anyway, it's not doing you any favours, but it's mainly the host immune response (often triggered by things like LPS from the gut) that causes cirrhosis. As I put it, "I'm not going to fight the dragon till I see two strong guys holding it down". And it seemed that day might have come. I thought, I'll go into this trial, and if I don't like anything about it, I'll just pull out, wait a bit longer. At best I'll clear the virus, at worst, well, knowledge has its own value to me.
The trial I went into was called VULCAN

Live Long and Prosper

VULCAN is a Phase III trial of Sofosbuvir (NS5B RNA polymerase inhibitor) and GS-5816 (pan-genotypic NS5A inhibitor), with or without ribavirin. Ribavirin might have been a deal-breaker for me - the people who got it suffered fatigue and depression - but I was lucky. I was randomised to receive Sofosbuvir (400mg) and the lowest dose of GS-5816 (25mg instead of 100mg), one pill of each once daily, and the trial was only to last 8 weeks. Would this be long enough? Would the low-dose GS-5816 be enough? Would my low-carb, high-fat diet help or hinder the drugs?
The interesting thing about GS-5816 is, that the viral protein it targets, NS5A, isn't just needed for replication, it's also one of the viral products responsible for HCV interfering with metabolism.

For example:
The nonstructural protein 5A (NS5A) encoded by the human hepatitis C virus RNA genome is shown here to induce the activation of NF-κB and STAT-3 transcription factors from its cytoplasmic residence via oxidative stress. NS5A causes the disturbance of intracellular calcium. Ca2+ signaling triggers the elevation of reactive oxygen species in mitochondria, leading to the translocation of NF-κB and STAT-3 into the nucleus. Evidence is presented for the constitutive activation of STAT-3 by NS5A. In the presence of antioxidants [pyrrolidine dithiocarbamate (PDTC), N-acetyl l-cysteine (NAC)] or Ca2+chelators (EGTA-AM, TMB-8), NS5A-induced activation of NF-κB and STAT-3 was eliminated. These results provide an insight into the mechanism by which NS5A can alter intracellular events relevant to liver pathogenesis associated with the viral infection.
It might be good to have a drug that would intercept those effects, even if it didn't kill the virus. GS-5816 might act as an antioxidant and antiinflammatory in people with active HCV infection. Unlike interferon and ribavirin, this was a drug that might potentially make you feel better, independent of its antiviral effect.

Anyway, I nearly pulled out of the trial when I got my information kit by email. GS-5816 had been tested in humans alright - for 1-9 days in healthy volunteers, and for 3 days in volunteers with HCV..
Here is the email I sent back:

after careful consideration I have decided not to take part in this trial. However I still want to be considered for future trials.
My reasons, in the event they may be useful to know, are as follows:
1) Efficacy. I understand from my reading that combinations including sofosbuvir have already proved effective in Gt1. It is reasonable to expect that they will be similarly effective and safe for Gt3. However this study appears to be trialing a novel combination to see if it is effective.

2) Safety. The novel drug GS-5816 has, if I read correctly, not been tested for longer than 9 days.

I have survived with chronic HCV infection since before 1991 and for the last few years have been able to thrive and recover my health. I would like to clear the virus, am prepared to take some risks to do so, including entering a Sofobuvir trial, but I only want to do this once. It appears to me from the studies your group has already published, and from the people I have met who have taken part in them, that there are Sofosbuvir combinations that, combined with my circumstances, would give me an excellent change of clearing HCV safely. It seems inevitable that these will be tested in a Gt3 patient group in the near future, and I would like to be considered for a trial of this description. If not, then I am confident I can manage my condition until the best product makes it to market.
Thank you for including me and for the very interesting reading material.

Well, they rang me up right away and talked me into coming in to see them. The information was out of date; of course people had since taken GS-5816 for long periods, because the trials were up to phase III now. And if anything had gone horribly wrong, Gilead would have cut their losses and moved onto the next drug. And I was impressed by how much the study doctors knew. They were virologists, not hepatologists, and they had worked out how to target the virus without involving the host. The drugs were specific for viral replication products, not for any part of my metabolism or immunity. That was what I wanted to hear.
I knew I wouldn't be allowed to take herbal medicines, but I wasn't prepared for the reason why. Because they might work. Now, herbal meds don't work that well against HCV. But neither do Sofosbuvir or GS-5816, taken on their own. It's only in combination that they deliver a 1-2 sucker punch. So any herb, with its weak effect, could still skew the result when combined with these guys. One or two, like St Johns Wort, could interfere in other ways. I was taking grape seed extract (OPCs) so I stopped that. I had to list whatever else I was taking:

Zinc 30mg as gluconate
Magnesium 150 mg as chelate
B2 25mg
Taurine 1,000mg

I was meant to keep taking these for the next 5 months (8 weeks treatment plus 12 weeks to SVR12) but stopped things I couldn't afford or didn't need any more, like the taurine. I used things like vitamin C and probiotics for short periods when I had a good reason.
They gave me an ECG, multiple blood tests, and sent me off for a fibroscan. The score was 7.4 which is moderately scarred (normal is under 5, cirrhosis is over 12). The blood tests were so hard, what with me having no normal veins left, that I was left out of the pharmacokinetic arm of the study.

My viral load at the pre-trial screening (22-Oct-13) was 600419 (log 5.78) which is fairly high for me, my ALT was 174. With a month to go before the trial started, I decided to get more serious about LCHF. Having a regular series of blood tests due meant I could check out whether going very low carb again would make any difference.
On the day the trial started (18-Nov-13), before the first dose, I gave blood again. Viral load 27167, log 4.43. That's the drop I associate, from previous experience, with being in, or near, ketosis, that is, under 50g carbohydrate/day (previous test was more like 100-150g/day). And, my ALT was 30. That was a big drop, lowest it had been since Hep C diagnosis in 1991. I didn't put that down to ketosis - more likely it was due to the zinc, which I'd started taking about 2 months earlier, based on this paper. It's also possible that stopping the grape seed extract helped. Phytochemicals that are hepatoprotective can sometimes become hepatotoxic. This happens with green tea extract, and I wouldn't rule it out with OPCs, which are chemically similar. Anyway, I started taking the Sofosbuvir and GS-5816.

I went back a week later (25 Nov 2013) - my viral load was less than 15 (log less than 1.18) meaning it was too small to measure by PCR. And my ALT and AST were 18. And that's the whole story really. My viral load stayed below 15, until the end of the trial (EOT) when it was undetectable (I missed the week 6 test so had no results between week 3 and the EOT. At week 4, which I read at EOT, VL was still detectable at under 15. So I had to wait till week 10, 2 weeks after EOT, to actually find out that I'd cleared the virus, or it became undetectable, sometime between week 4 and week 8).
At week 8, EOT I had another fibroscan. 5.5, down from 7.4. During the course of treatment my scarring had significantly regressed. That is amazing.

Side effects? I had a few, but then again too few to mention. For the first week my skin felt dirty and gritty, and my girlfriend said I was over-sensitive. Maybe true, but I think there was some confirmation bias involved. She hadn't liked me jumping into this experimental drug trial without really consulting her, and I can't say I blame her. I'm sorry I was pigheaded enough to put her through that anxiety. After that, I had a sore throat, cough, a bit of laryngitis, and a swelling under my tongue. And I could taste the drugs all the time. But after week four, nothing at all. The last 4 weeks was a breeze. And, from the start, I was sleeping better, and my energy level was good. There were not serious side effects and I never considered stopping the trial. And I say that as a total hypochondriac who couldn't stand to take aspirin or antibiotics for 8 weeks.

It's week 8 after treatment, so in another month I'll know about SVR12. I have met one person who relapsed after successful treatment on a similar combo, a very unusual outcome so far, but I've had all the advantages they didn't have. But you know, if this didn't work out, I would have no hesitation about trying a longer course, a higher dose, a different combo. It's been no sweat. Amazing. Pharma made something that worked, cured a disease that, as far as I'm concerned, had no cure before.

It can be done.

"I forget most of what I have read, just as I do most of what I have eaten, but I know that both contribute no less to the conservation of my mind and my body on that account." - Georg Christop Lichtenberg on food frequency questionnaires.

I've procrastinated about this ever since Peter Hyperlipid posted his own classic eating update a while back, trying to contextualize what purpose a similar post of my own might serve. Ah-Ha! I see. OK then.
Basically, it's good to know these things can be done, are being done, and the reasons for certain decisions are probably worth revisiting.

Music by Mink - a lost treasure from 1996, "Your Bad Example".

Wake up - too early, give a brother some rest, my start is 6am these days which means coffee. Strong with cream and maybe if it's too strong a little soft brown sugar but, like, 1-2g, which is plenty sweet if you eat low carb, yet not enough to contribute to the world's fructose problem. Might have 2 or 3 coffees like this in the day (almost all without sugar). If it's instant coffee I'll stick a teabag in it because - I should have taken out a patent - this makes instant coffee taste like fresh coffee. Yup, I'm a wild and crazy guy, livin' on the edge now.

Coffee, as any fule kno, has powers to protect the liver in every study you can think of, and enhances the response to combination therapy in Hep C. Nice work if you can get it, as a poor liver function can slow caffeine metabolism and make you intolerant of coffee. So a little chicken-and-egg but still, there are solid biochemical reasons why both caffeine and coffee polyphenols of the caffeic acid family ought to inhibit fibrosis etc. (for example, caffeine blocks adenosine receptors, adenosine released from damaged cells serves as a chemoattractant "stop" signal for hepatic stellate cells, these cells remodel collagen matrix, caffeine is switching off their GPS. Caffeic acid phenethyl ester, CAPE, which you will also find in propolis and which is a normal metabolite of other dietary polyphenols, inhibits HCV replication. And so on.)

Other drinks I might enjoy, because I don't drink coffee after the early afternoon, include well water, green tea, black tea, red bush tea (aspalanthus, rooibos) or hibiscus flower.

Breakfast I will try to have at 10am. I used to be stricter about food-window IF but now that my appetite is tamed I'm more concerned with getting sufficient energy so will eat outside of opening hours if I feel hungry. And if I'm going out for the day I have to eat early anyway. Breakfast is fairly consistent:
3 rashers bacon (chopped small), or occasionally most of a tin of sardines (the dog gets one) or a few kidneys or a chicken liver or two. Fried slowly in a tablespoon of beef and lamb dripping (AKA tallow). This takes care of excess PUFA in the bacon, as I add one large tomato, chopped (for the potassium and carotenoids), a tablespoon of butter (or two or more if I need extra energy), a teaspoon of crushed garlic, 2 (or 3) egg yolks, a bit of any gelatine broth I have lying around, spice and salt if needed. (Note; I use various pre-mixed Indian spice mixes, masalas. I only buy masalas that contain salt - chat - as an ingredient, as this shows attention has been paid to creating a rounded flavour). So any linoleic acid in the bacon or yolks has been diluted by the more saturated fats of the dripping and butter and shouldn't matter in the greater scheme of things.

Snacks - might or might not want these in the afternoon, which might be 25g dark chocolate, or a handful of almonds, 4 Brazil nuts for the selenium, or some cold meat left over from the night before. Probably a little fruit too; at the moment, that's mandarins, kiwifruit, persimmons. Used to eat cheese but I'm a bit allergic so trying to quit. If it's a higher-carb day - or I feel like it - I'll have a banana.

Dinner (served around 6pm): some meat (could be lamb shoulder chop, if it's chicken I'll stuff it with bacon, rolled oats, butter, sage, onions and fish sauce to up the SFA content). Or could be chicken or fish cooked in coconut cream. Or beef shin bone slowly cooked in a stew with one potato, carrots, onions.
But assuming it's the lamb chops, then a lower-carb vege good for fat-soaking will be roasted with them. Pumpkin, sweet potato, oca yam, whole garlic. Roasted Brussels sprouts are pretty special IMO. Any greens - leek, Chinese cabbage, spinach - will be comfited in butter (fried slowly with lots of butter till it goes soft). Boiled carrots, steamed green beans, mashed parsnip with cream, roasted beetroot are optional but welcome. I probably eat about 200g meat, which supplies about 40-50g protein. I prefer ruminant fat, so if the meat is chicken or pork I'll find a way to include more butter or dripping in the veges. I'm not against olive oil but find I have fewer occasions to eat it.

I'll have a cup of black tea after dinner because of some superstition about iron absorption, though I tend to agree with G. C. Lichtenberg, the best thing you can add to a meal is to remove drinking from the experience.

Dessert might be 2 teaspoons Bourneville cocoa mixed to a paste with cream and 1-2g soft brown sugar. A mousse of sorts I think. Occasionally mix up some kelp powder, spirulina powder, and olive oil to a paste and eat for iodine fix. Not pleasant but miles better than iodine deficiency, which will seriously mess you up. I also use the iodised table salt. I wish someone would add the iodine supplement to unprocessed sea salt.

Calories? I dunno. One day I sort of counted and it came to 1,800, so since then I've tried to stop undereating. Carbs? Probably 50g, not often more than 100g. But all starchy carbs are eaten at the evening meal, and with plenty of fat, so the GI and insulin rise is limited. And I do notice, over time, that this has left me feeling healthier and more energetic in the evenings. I try to stay out of glycogen-depleting ketosis but well below the supposed daily requirement of 150g glucose. Actually I would find it hard to eat 150 carb grams in a day with this diet. I don't often eat potatoes or rice, and I'm sceptical that resistant starch is a type of fibre I need. I do occasionally eat small amounts of oats at the moment. I figure that my Scottish genes - and my years of abstaining from wheat and rye - are enabling me to do this with seeming impunity.

I don't usually exercise for the sake of exercising, but I do run or jump or climb or whatever because I feel like it sometimes. Walking up big hills or small mountains is probably the most energetic thing I do, and swimming in the summer. My house is up a steep drive and a few flights of steps and I run up those rather than walk the boring slow way. Instinctive exercise, like instinctive eating, is what works best for me; attempts to develop my strength capacity tend to result in avoidable injuries, and it seems to be developing satisfactorily anyway.

Supplements - vitamin D and K2, magnesium 150-300mg, vitamin C 1g, occasional probiotics, very occasional low-dose multivitamin. I'd take selenium 100-150mcg if I didn't have Brazil nuts and would supplement zinc if I could find a cheap one with no B6.

So what we have here is Atkins-type macronutrient tinkering, tweaked for the effect on microbiota. Which is like "Phase 2" of any long-term diet plan (see Art Ayer's "Cooling Inflammation" link at the right).
So what do I make of the fact that high-fat diets can produce unwanted LPS elevations in rats and humans eating their respectively standard rat and human chows?

The quality of fats is important. Extrapolations from rodent diets where fats are 30% PUFA, are all extrinsic fats, carbohydrate is still a major part of energy as pure sugar and starch, and types and amounts of fibre are limited are only relevant to similar human diets; these rat diets often resemble cheesecake recipes.
My belief is that a high-fat diet (butter, fish, eggs for cholesterol and choline) can be used to restrict bacterial overgrowth (via higher levels of bile and stomach acid) and set the scene for the right fibre and probiotics to work. Further, butter is a good source of butyrate (about 3-4%), which means 100g butter contributes about as much butyrate as 6-8g dietary fibre on a good day without the risk of a non-specific prebiotic effect. My strategy is to cook whenever possible fibrous vegetables (pumpkin, greens, sweet potato, tomato, parsnip) with butter (as you will find in French quisine) which seems to work well.

Music - Mascagni, the "octopus aria" (Aria della poivra) from Iris.

For the last wee while I've been helping Prof Grant Schofield and his team write a response to the New Zealand dietary guidelines (low fat, high grain, no SFA).
The paper is the PDF linked to in this post.

http://profgrant.com/2014/04/23/the-real-food-guidelines/

The first time I've had my name on a scientific submission, and a fine one it is too, with the collected wisdom of a bunch of scientists from various disciplines, all working together, to a deadline (we had only a few days warning about the new guidelines, and received no background material on the scientific evidence used in their making). I'm proud of what we achieved, see what you think, and spread this document around.

George Henderson

"Everyone should eat what I eat, 'specially cats!"

Working on the "Real Food" AUT dietary guidelines submission it became clear that neither the epidemiology of the lipid hypothesis nor the RCT experiments testing it were designed to separate the supposed artery-clogging effect of saturated fat from the purported heart-healthy effect of polyunsaturated fat.
What we had was a series of comparisons of higher SFA and lower PUFA vs. lower SFA and higher PUFA. There were no investigations of either higher SFA in a diet with optimal PUFA, or of deficient PUFA in a diet also low in SFA.
The former of these, higher SFA in a diet with optimal PUFA, is what the low-carbohydrate, high-fat (LCHF) diet supplies. The latter is a danger on a low-fat diet, so "let them eat margarine".

1946 Dietary Guidelines - not bad at all.

Richard Lehman described the mindset in a recent BMJ blog:
If I despair of meta-analyses, what can I say about dietary surveys? Actually, they’re quite fascinating, though they rarely bear any definable relation to human health. Diet and religion are often closely aligned. The authors of this paper have got religion bad: “Diet is one of the fundamental risk factors for health, disease, and disability in the world. Indeed, given that trends in metabolic risk factors such as blood pressure, cholesterol, glucose, and body mass index are being largely driven by nutrition, suboptimal diet is the single leading modifiable cause of poor health in the world, exceeding the burdens due to tobacco and excess alcohol consumption combined.” They then go on to look at fat. Why, I know not. But it is quite interesting to see which countries eat what types of fat. Where people eat more saturated fat, they often eat more unsaturated fat. For all I know this may help to explain why nearly everyone everywhere is enjoying their food more and living longer.
In the paper Richard Lehman is discussing, we find the alarming statement that the Centre for Disease Control (which really should be worrying more about emergent viruses and antibiotic-resistant bacteria and less about fat) thinks that getting 13% of our energy from linoleic acid (omega 6 PUFA) will be "optimal". If that's optimal, what do they consider an excess? This crazy figure is certain to be based on the amount of linoleic acid required to reduce serum LDL to a particular "healthy" target across a Western population, with no thought given to metabolic health, and bearing no relation to any intake humans might have been exposed to for any period in their evolutionary history.

As Peter D. said in a recent comments thread, "You have a basic assumption that blood lipids cause CVD. You will make many wrong choices based on this hypothesis." Now, I don't know what causes CVD. It could be blood lipids - there are intelligent people who think that small, dense LDL particles typical of refined-carbohydrate diets rip up the arterial walls like stilettos on a ballroom floor. But I do know that the assumption that blood lipids cause CVD has led to many wrong choices. Wrong choices in the supermarket. Wrong choices in the design of experiments. Wrong choices in the interpretation of epidemiological data. Imagine what useful drugs statins might be if they were not over-prescribed on the basis of LDL counts, with results like this.

Many analyses of the "lipid hypothesis" epidemiology and RCTs failed to distinguish between omega 6 and omega 3 PUFA, or between vegetable PUFA (linoleic acid and alpha linolenic acid) and long chain polyunsaturated fats found in animal foods like EPA, DPA, DHA and arachadonic acid. This is understandable because, when Ancel Keys cooked up the lipid hypothesis, no-one knew that omega 3 fatty acids existed, let alone that they were essential nutrients. I'm not even sure if anyone realised that omega 6 was essential back then.
We are stuck with an article of faith from the Dark Ages. A diet high in saturated fats that happens to be deficient in polyunsaturated fats - say with fats supplied exclusively from tallow and hydrogenated shortening, with over-cooked boiled meat or deep-fried fish, milk, boiled greens, sugar, and highly refined grains - which was the mid-20th century diet for many in the Westernised world - can be deficient in PUFA. Smoking and drinking and the general lack of antioxidants in the diet, as well as the effect of insulin from the refined carbohydrate, will tend to squander what PUFA there is. Not surprising if this population has more CVD. What will be surprising is, if the saturated fat has anything to do with it. That diet will also be high in monounsaturated fat (beef olein is the MUFA from tallow, used in old-school chip shop fryers), but somehow MUFA gets a pass. It's all very unsatisfactory.

Is there any research that can help us sort out the difference between a lack of PUFA and an excess of SFA? Well, maybe. We can at least see the difference between an excess of PUFA, and a lack of SFA.This study by Amin A. Nanji and Samuel French is an ecological study comparable to Ancel Key's "7 Countries" study, except that it includes 17 countries.
Mortality from cirrhosis in many countries deviates markedly from that expected for a given per capita alcohol intake. We investigated the possibility that dietary factors might explain the deviation expected and actual mortality rates in different countries. Deviations from expected cirrhosis mortality was calculated as a percentage for 17 different countries, all of whom had carrier rates for hepatitis B virus of less than 2%. The percentage of deviation was correlated with dietary intake of saturated fat, polyunsaturated fat, cholesterol, and also with mortality from ischemic heart disease. The percentage of deviation correlated inversely with dietary cholesterol (r= -0.86, p 0.001) and saturated fat (r= -0.80, p 0.001) and positively with polyunsaturated fats (r= -0.55 p 0.05). This suggests that both saturated fat and cholesterol protect against alcoholic cirrhosis while polyunsaturated fats promote cirrhosis. The correlation between percentage of deviation and ischemic heart disease (r= -0.78, p 0.002) suggests that those factors that promote ischemic heart disease protect against alcoholic cirrhosis.

If the factors that promote IHD protect against alcolohic liver disease (ALD), what are they? We can perhaps discard the red herring of cholesterol, which is a marker for animal fat, and which indicates consumption of foods (such as eggs) which are also rich in the essential hepatoprotective nutrient choline. Cholesterol does protect against ALD tested separately, but coconut MCTs (no cholesterol, no PUFA) gives the same protection as tallow (cholesterol, 1% PUFA) when the two are compared.
There has been a large body of animal experimentation designed to elucidate the link between alcoholic liver disease and dietary fats, with occasional testing of acetaminophen (paracetamol) toxicity in the same model. These papers have been analysed expertly by Victoria Prince on her blog and I will not duplicate her efforts.
http://principleintopractice.com/2012/07/23/liver-and-lipids/
http://principleintopractice.com/2012/08/02/liver-saving-saturated-fats/It can quite clearly be seen in Victoria Prince's third liver-and-lipids post below that there are mechanisms whereby saturated fats can have health benefits, distinct from the restriction of PUFA, because saturated fats from coconut and cocoa protect the liver in different ways.
"Thus it seems that dietary MCTs work in a way that maintains the expression of gut tight junction proteins, preventing endotoxin from making it into the circulation, while long chain saturated fats work in a way that increases endotoxin-binding proteins in the liver. Both prevent endotoxin-induced damage in the liver, but in very different and distinct ways." This is not just relevant to alcoholics and people who consume paracetamol; the fact that long-chain SFAs make the liver less sensitive to LPS is relevant to the studies showing serum markers of dairy fat intake are associated with diabetes protection, because liver inflammation is a precursor to diabetes. And the fact that MCT, made from fats you can only get in significant amounts from coconut or dairy fat, maintains the integrity of the gut, is relevant to the epidemiological studies showing that children who eat margarine and drink low-fat milk have a higher rate of allergies and asthma compared to children who eat butter and drink full-fat milk.
Saturated fats are good for you. Get over it.
http://principleintopractice.com/2013/12/27/chocolate-and-coconut-for-health/

The high fat model of alcoholic liver disease was developed because rats fed normal chow plus alcohol would not develop ALD. The researchers concluded that polyunsaturated fats are "essential for the development of alcoholic liver disease", and that saturated fats are protective.
Diets enriched with saturated fatty acids protect against alcohol-induced liver injury, whereas diets containing polyunsaturated fatty acids promote liver injury (Nanji and French, 1989; Nanji et al., 1989, 1994a). Saturated fatty acids have also been reported to reverse established alcoholic liver injury (Nanji et al., 1995, 1996,1997b).
Now, the fats that promote liver injury are vegetable oils, typically in these tests corn oil and soy oil*. Thanks to the campaign against saturated fats, these are the kind of oils that the fast food eaten by drunken New Zealanders is prepared with today. This seems to be a failure in public health planning.

"You have a basic assumption that blood lipids cause CVD. You will make many wrong choices based on this hypothesis."

(*interestingly fish oil, which has a stronger association with CVD prevention than omega 6, also has a greater promoting effect on alcoholic liver disease, albeit in quantities many times greater than anyone would ever include in their diet. And deficiencies of PUFA, particularly AA, EPA, and DHA, also play a part in ALD, so Samuel French suggsts that alcoholics be advised to replenish these fats by eating "Mediterranean diet" type foods whenever they're in recovery).

The rat model of alcoholic liver disease demonstrates that in this case the effects of high PUFA, while they can be confused with those of low SFA, are not the same. It also demonstrates that the SFA/MUFA ratio of the non-PUFA fat makes little difference (olive oil is almost as protective as beef tallow against acetaminophen liver damage; it seems an oversight that olive oil has not been included in the alcohol experiments, considering how widely it is consumed).
The link between SFA and CVD disappears when SFA is considered separately ("monotonically"), rather than as a marker for PUFA deficiency. The protective association between omega 3 PUFA (the PUFA less likely to be optimal) and CVD remains about the same when these nutrients are considered monotonically, as in the 2013 Singapore Chinese Health study by Koh et al. People who ate more DHA, EPA, and ALA had significantly lower rates of CVD mortality - and they also ate more saturated fat, monounsaturated fat, and omega 6 PUFA, all increasing stepwise with omega 3 across the quartiles as CVD mortality decreased. "Where people eat more saturated fat, they often eat more unsaturated fat. For all I know this may help to explain why nearly everyone everywhere is enjoying their food more and living longer."
The inverse association between omega 3 and CVD (0.83 OR) is seen with total omega 6 intakes of, on average, 9.9g per day, or 4-5% of energy - almost exactly the same as healthy New Zealanders ate in this paper, and much less than the crazy CDC projection of 13%. All things being equal, the people who eat the most fat, assuming they are not eating solely hydrogenated industrial fats or exclusively low-PUFA fats such as tallow, but are instead getting some fats from wholefoods, including fish, are surely eating enough PUFA to have an optimal intake for CVD prevention, regardless of any effect on blood lipids.

Polyunsaturated fats are essential nutrients, but also highly reactive and bioactive molecules. This means that the association between intake and mortality will follow a fairly steep U-curve, with a "sweet spot" in the middle. Saturated fats are inessential nutrients with low reactivity. The association curve between intake and mortality is likely so flat my dog could skate it.

(not my actual dog)

PUFA, MUFA and SFA occur together in whole foods and in traditional fats and oils. They are not easily separated, even in the laboratory. You can buy pure sugar for a few dollars in the supermarket, it's easily separated from the foods it occurs in, usually to be ladled back into some other food in excessive quantities. You can probably buy purified long-chain saturated fats like palmitic acid from Sigma Aldrich if you have the money and inclination, and MCT is a processed form of medium-chain saturated fat that is sometimes supplemented by ketogenic dieters; I've never seen it, but I've heard it's expensive.
Most people eating a LCHF diet, even those who think "saturated fat is good for you", are not going to go that far. Few are even going to use butter or coconut oil as their only fats, and anyone eating a variety of wholefoods that have been made palatable but not cooked to death is likely to have an optimal PUFA intake, whatever that is.

This is just a bookmark for three responses to two recent incidents of press censorship.
ABC withdrew the two episodes of "Heart of the Matter" Catalyst show, despite nothing substantial in the complaints being upheld, and the BMJ retracted some comments critical of statins, including those of Dr Aseem Malhotra, which were opinion based on his clinical impression, and had been presented as such.

[EDIT: This BMJ comment thread supplies all the information anyone might need to know about statin side effects. The patients' stories in particular.]

This is from Uffe Ravnskov's newsletter:

Why are the media afraid of revealing the greatest medical scandal in modern time?

In my October 2013 Newsletter I told you about the Australian TV program "Heart of the matter" produced by Maryanne Demasi, a PhD in medical science and a science reporter and presenter with Australian Broadcast Corporation (ABC)¨s catalyst. In the program she interviewed several experts about their view on the effects of cholesterol-lowering diets and statin treatment. As far as I know this is the first TV program in the western world where critics of the cholesterol campaign have been allowed to present their view in detail. The shrewish reactions from the National Heart Foundation and from the drug companies were therefore predictable.

In accordance with their Code of Practice and the editorial policies ABC asked the Audience and Consumer Affairs (A&CA) to examine the critical comments. Eleven critical points were examined, but although ten of them were cleared of bias, the ABC declared that the programs have been removed from the ABC website, because the A&CA has concluded that some parts of the program breached ABC standards on impartiality.

Their decision is most curious because the A&CA did not find any factual information wrong. For instance, in their report you can read the following about the first episode “The dietary villains”:  

1. The factual information in the program was accurately presented and the reporter has demonstrated that she diligently sought and considered a variety of views on the subject. No material inaccuracy has been demonstrated by any complainant.

2. The principal perspectives were presented.

3. Neither position was endorsed by the program.

4. Neither perspective was misrepresented.

5. The nature of the program necessitated that the unorthodox theory was given more time and explanation. The Code does not require that they receive equal time, nor that every facet of every argument is presented.

With one exception similar conclusions were made about the second part. I shall come back to the exception that breached the ABC standards.

The objections reveal that either the complainants have an alarming lack of knowledge or that they consciously try to mislead. Here come a few examples; in a complicated 49 pages document from ABC you can read all of them.

“The hypothesis that eating saturated fats can increase cholesterol levels which in turn can cause heart attacks is widely accepted by the medical community.”

It is true that it was accepted many years ago, and most doctors and lay people still think it is true. However, more and more researchers have realized that it is totally wrong. Furthermore they would have known it already sixteen years ago if they had read my review about this issue, or my review from 2010 or a more recent one by Robert Hoenselaar or the recent meta-analysis by Chowdhury and coworkers“

Sadly, as it appears from the following, the complainants seem to be unfamiliar with the most simple facts of biochemistry.

"It was mentioned that those molecules which contain long chains of single carbon bonds are more stable than those containing numerous double bonded carbon groups. Students doing high-school chemistry will be able to tell you the fault in this statement.”

As I told you in my February 2013 newsletter this is a fact. Any well-informed student will also be able to tell you that, and if anyone still thinks that the authorities cannot be wrong, any textbook in biochemistry can tell you that they are.

Several complainants argued that the viewers were misled because some of the interviewees “had businesses promoting nutrition based products, diets, books and supplements that constitute conflicts of interest”.

But as Dr. Demasi pointed out, everyone interviewed had a conflict of interest including Ass. Professor David Sullivan who is a member of several advisory panels within the pharmaceutical industry and he has also received research grants from several statin-producing drug companies. Furthermore Dr Robert Grenfell, another supporter of the cholesterol campaign who was interviewed in the program, is Director of the National Heart Foundation, which has received millions of dollars from pharmaceutical companies for research, scholarships and fellowships.

“The pharmaceutical industry was accused of ‘criminal’ conduct akin to ‘organised crime’. Medicines Australia strongly rejects such accusation and feels that it is unfair (sic) characterisation of Australia’s medicines industry.”

Haven´t they read Peter Gøtzsche´s book Deadly Medicines and Organized Crime? Or the recent article in The Independent? Have they forgotten the VIOXX scandal? Have they forgotten the criminal behavior of Pfizer?

Most pages were about the questioning of the benefit of statin treatment. As one of the complainants wrote: It is a fact that appropriate cholesterol interventions are very powerful in preventing cardiovascular disease. And in a letter to Dr. Demasi the National Heart Foundation wrote: The mass of evidence suggests that…statins reduce the risk of death or cardiovascular events in populations without a history of CVD, irrespective of age and gender and across a wide range of cholesterol levels.

If you think this is a fair statement, read my newsletters from May 2013, August 2013, September 2013 and November 2013 The simple fact is that no statin trial has been able to prolong the life for women or for people without coronary heart disease. Therefore, if you are a doctor and you have a heart-healthy patient who want to lower jhis/her cholesterol, tell the patient the following: “Your chance not to get a non-fatal heart event during the next five years according to Cochrane is about 97 per cent. You can increase your chance to 98 per cent if you take a statin every day. But then your risk of suffering muscle problem is at least 20 per cent unless you never exercise; your risk of becoming sexually impotent is about 20 per cent; your risk of suffering from diabetes is about 4 per cent, and you also run a risk of memory loss, liver damage, peripheral neuropathy, cataract, and even cancer, but we do not yet know how large these risks are. And don´t forget than many non-fatal events may heal with little future discomfort or none at all.”

Now to the reason why the program was removed.

One of the rules in ABC´s Code of Practice is the following: Do not unduly favour one perspective over another. But how could Dr. Demasi be able to do otherwise??? I mean, if the members of A&CA acknowledge that all the critical remarks from the opponents of the cholesterol campaign were true, and If the proponents are unable to present any relevant counter-arguments, how could A&CA state, as they did, that some parts of the program breached ABC standards on impartiality? 
  A&CA suggested that Catalyst should add extra information to the website to provide more balance. They did not recommend to strip the stories off the website. This decision was made by ABC management. The question is why? Some speculate that it was political pressure from the drug industry or the Heart Foundation or it was an action to avoid more controversy.Fortunately both programs are still available on Youtube. Here is part one, and here is part two.

Uffe Ravnskov, MD, PhD, independent investigator

Spokesman of THINCS, The International Network of Cholesterol Skeptics

Magle Stora Kyrkogata 9, 22350 Lund, Sweden

Assem Malhotra's response to the BMJ statins censorship is here:

And Zoe Harcombe's analysis of both matters is here:

Diabetes and dairy fat in India.

The epidemics of diabetes, cardiovascular disease and related conditions in India have been called iatrogenic (Raheja B.S. 1994), a product of diets high in linoleic acid as a result of “chasing the phantom of cholesterol” (Raheja et al. 1993). The traditional Indian diet (39% fat) supplied 20.3%E as saturated fats, mainly from ghee, with 5% from linoleic acid. Concerns that this diet is atherogenic have resulted in replacement of ghee with high-linoleate oils; the modern urban diet being 31.9% fat, with 5.6%E as saturated fat, and 16.9% linoleic acid (Raheja, B.S. et al. 1993).

In children and young individuals, a high intake of n-6 PUFA is correlated with fasting hyperinsulinaemia, and dietary supplementation with n-3 PUFA leads to an improved lipid profile but not insulin sensitivity. In adults, high-carbohydrate meal consumption was reported to cause hyperinsulinaemia, postprandial hyperglycaemia and hypertriacylglycerolaemia. (Misra, A. 2009).

The association of ghee consumption in the Indian diet with a lower rate of diabetes is consistent with the correlation between serum markers of dairy fat consumption and reduced diabetes risk (Mozaffarian et al. 2010, 2013). The NZ Ministry of Health currently recommends a wide range of linoleic acid and alpha-linolenic acid in the diet; the lower recommended intake of LA being 4%, the upper being 10%, and the lower recommended intake of ALA being 0.4%, the upper 1% (the omega 6-3 ratio at median intakes thus being 10:1). Saturated fat intake below 10%E is recommended. (Food and Nutrition Guidelines for Healthy Children and Young People (Aged 2–18 years): A background paper. 2012 MOH).

The message from the Indian researchers into the causes of their diabetes epidemic is that higher consumption of dairy fat protected marginal dietary omega-3 intake from abrogation by excessive intakes of omega-6 fatty acids. Replacing highly saturated dairy fats with diets higher in linoleic acid and refined carbohydrate, which is the same effect that the campaign against saturated fat has had among more disadvantaged New Zealanders, has increased the rate of diabetes, which is consistent with the New Zealand experience, suggesting that the increased incidence of diabetes in New Zealand has been in large part an iatrogenic phenomenon.

"The present epidemic of DM and ACVD in Asian indians and possibly in other communities is iatrogenic resulting from what may be called modern malnutrition due to increased intake of total and n-6 fats and decreased intake of n-3 fat and antioxidants. Such a diet induces oxidative stress and activates the immune system. Imbalance between n-6 and n-3 fats result in inappropriate immune response. It also leads to increased and unbalanced biosynthesis of metabolites of n-6 fats. These are immune suppressive, proinflammatory and thrombogenic. They also contribute to insulin resistance and dyslipidemias. This makes DM and atherosclerosis as malnutrition related oxidative immune inflammatory disorders. Various risk factors are also the result of the same inappropriate response. Our intervention studies give considerable support to this hypothesis. It is suggested that simple correction of diet defects can reverse the disease process and thereby offer a simple, practical therapeutic option not only for the primary prevention of each of these disorders or their complications but also for the so called risk factors for these diseases. It is suggested that the real remedy for DM, ACVD and all the risk factors lies not in drugs or surgery but in the kitchen."
- B. S. Raheja

Misra, A. et al. (2009). South Asian diets and insulin resistance. Br J Nutr. 2009 Feb;101(4):465-73. doi: 10.1017/S0007114508073649

Mozaffarian, D. et al. (2010). Trans-Palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in US Adults. Ann Intern Med. Dec 21, 2010; 153(12): 790–799. doi: 10.1059/0003-4819-153-12-201012210-00005

Mozaffarian D. et al. (2013). Trans-Palmitoleic acid, other dairy fat biomarkers, and incident diabetes: the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr. 2013 Apr;97(4):854-61. doi: 10.3945/ajcn.112.045468.

Raheja B.S. (1994). Diabetes and atherosclerosis as immune-inflammatory disorders: options for reversal of disease processes. J Assoc Physicians India. 1994 May;42(5):385-90, 395-6. PMID:7829439

Raheja, B.S. et al. (1993). Significance of the N-6/N-3 Ratio for Insulin Action in Diabetes. Annals of the New York Academy of Sciences, 683: 258–271. doi: 10.1111/j.1749-6632.1993.tb35715.x

Food and Nutrition Guidelines for Healthy Children and Young People (Aged 2–18 years): A background paper. (2012) New Zealand Ministry of Health.
http://www.health.govt.nz/system/files/documents/publications/food-and-nutrition-guidelines-for-healthy-children-and-young-people-p4.pdf

Why does dairy fat, and perhaps other similar fats like tallow and coconut, seem to prevent diabetes?
A broken omega 6:3 ratio becomes more likely with higher PUFA intakes. There is something about having a low PUFA intake that preserves the balance, even at relatively low omega 3 intakes.
We can see this in the recent fatty liver study comparing olive oil with canola oil and soy/safflower oil (control). For 6 months 20g of oil per day was used to cook food; this is not much (and it seems likely to me that many participants would have used more than they were directed to, if only to increase the palatability of their meals). There was no change in fatty liver and insulin resistance scores in those using soy/safflower oil, which is presumably what all subjects cooked with before.

The pre- and post-intervention difference in liver span was significant only in the olive (1.14 ± 2 cm; P 0.05) and canola (0.66 ± 0.33 cm; P 0.05) oil groups. In the olive and canola oil groups, post-intervention grading of fatty liver was reduced significantly (grade I, from 73.3% to 23.3% and from 60.5% to 20%, respectively [P 0.01]; grade II, from 20% to 10% and from 33.4% to 3.3%, respectively [P 0.01]; and grade III, from 6.7% to none and from 6.1% to none, respectively). In contrast, in the control oil group no significant change was observed.

So canola oil and olive oil were about equally good for reversing steatosis; this might be an expected effect of supplying fats with an omega 6:3 ratio of 2:1 for six months. But when it came to glucose and insulin, there was a marked difference:
In a comparison of olive and canola oil, a significant decrease in fasting insulin level, HOMA-IR, HOMA-βCF, and DI (P 0.001) was observed in the olive oil group.
In fact, fasting insulin and blood glucose were normalised in the olive oil group, but not in the canola oil group. With regard to these measures of glycemic control, a 50% lower intake of linoleic acid (with substitution of MUFA from oleic acid) produced more benefit than a 20-fold increase in alpha linolenic acid.

Here we have a paper that compares the effect of LA restriction (from 8%E to 4%E) with the effect of DHA in immune-deficient mice bearing human breast cancer cells;
Tumor prostaglandin E2 concentrations were reduced by feeding the lower LA level; further dose-dependent decreases occurred in the DHA dietary groups and were accompanied by reduced levels of 12- and 15-hydroxyeicosatetraenoic acids.
According to Raheja et al. (1993) "prostaglandin E2 is a potent inhibitor of first-phase insulin release, whereas an arachidonic acid lipoxygenase product, possibly 12-hydroxyeicosatetraenoic acids (12-HETE) sustains increased second-phase insulin release". A pattern also known as insulin resistance, or if sufficiently elevated, NIDMM or type 2 diabetes. These elevated prostaglandins are also seen in type 1 diabetics.
And, what do you know, ghee reduces PGE2 in Wistar rats:
Ghee, the anhydrous milk fat, is one of the most important sources of dietary fat in India. Male Wistar rats were fed diets containing 2.5, 5.0 and 10 wt% ghee for a period of 8 weeks. The diets were made isocaloric with groundnut oil. The results showed that serum thromboxane levels decreased by 27-35%, and 6-keto-prostaglandin F1alpha by 23-37% when ghee was incorporated at level of 10% in the diet. Prostaglandin E2 levels in serum and secretion of leukotrienes B4, C4 and D4 by peritoneal macrophages activated with calcium ionophore decreased when increased amounts of ghee from 2.5 to 10% were included in the diet. Arachidonic acid levels in macrophage phospholipids decreased when incremental amounts of ghee were fed to rats. These studies indicate that ghee in the diet not only lowers the prostaglandin levels in serum but also decreases the secretion of leukotrienes by macrophages.

(I haven't seen fulltext for that, but control, groundnut oil, is around 30% LA, and 10 wt% will be more than 10%E).

With regard to ALA, this epidemiological paper on prostate cancer, while perhaps irrelevant, has an interesting line:ALA intake was unrelated to the risk of total prostate cancer. In contrast, the multivariate relative risks (RRs) of advanced prostate cancer from comparisons of extreme quintiles of ALA from nonanimal sources and ALA from meat and dairy sources were 2.02 (95% CI: 1.35, 3.03) and 1.53 (0.88, 2.66), respectively. The multivariate RR of advanced prostate cancer from a comparison of extreme quintiles of the ratio of LA to ALA was 0.62 (0.45, 0.86).
Do you have any idea how much dairy fat it takes to get into a high quintile for ALA? Anyway, just another epidemiological paper where animal fats come out safer than their vegetable equivalents. One of the ones you don't hear about.
As I mentioned previously here, in New Zealand per capita weekly butter consumption at the beginning of the Second World War was 415 grams. It is now 112 grams, which is half of the reduced 1940s wartime ration. Not much Type 2 diabetes in New Zealand prior to the Second World War. Not much consumption of heart-healthy oils either, but plenty of consumption of sugar and white flour.

The second hit: In children and young individuals, a high intake of n-6 PUFA is correlated with fasting hyperinsulinaemia, and dietary supplementation with n-3 PUFA leads to an improved lipid profile but not insulin sensitivity. In adults, high-carbohydrate meal consumption was reported to cause hyperinsulinaemia, postprandial hyperglycaemia and hypertriacylglycerolaemia. (Misra, A. 2009).
Take a child, and raise them on this high-LA, vegetable oil diet (because saturated fat and high cholesterol, don't you know, cause heart disease in toddlers). By the time they reach adulthood, they'e primed for the second hit:

Refined grain consumption and the metabolic syndrome in urban Asian Indians (Chennai Urban Rural Epidemiology Study 57).

Compared with participants in the bottom quartile, participants who were in the highest quartile of refined grain intake were significantly more likely to have the metabolic syndrome (odds ratio, 7.83; 95% confidence interval, 4.72-12.99). Higher intake of refined grains was associated with insulin resistance and the metabolic syndrome in this population of Asian Indians who habitually consume high-carbohydrate diets.

That's grains, by the way, not sugar, not HFCS.

Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not β-cell function in humans.

The lipid hypothesis, as evry fule kno, predicts that eating saturated fat causes elevation of serum cholesterol or LDL which then plays a causal role in cardiovascular heart disease. How or why no-one knows but the feeling out there is that saturated fat causes bad cholesterol and heart disease. The notion is, as they say, entrenched; it is a meme more widely believed now than any religious dogma.

Unlike the unknowable nature of God, the lipid hypothesis can be disproved by multiple lines of evidence. Here is one.

Animal fat is a blend of saturated fats, monounsaturated fats, and polyunsaturated fats. Polyunsaturated fats lower serum cholesterol, monounsaturated fats have no effect on serum cholesterol, and some saturated fats also have no effect on cholesterol. William Barendse describes the set-up eruditely and eloquently in his epic review“Should Animal Fats be Back on the Table? A critical review of the human health effects of animal fat” as follows;

“As an example from one of the hardest animal fats, approximately only 27% of tallow from pasture-fed beef is cholesterol-increasing saturated fatty acid (CISFA) (Yang et al. 1999b), i.e. chain length of 12–16 carbons, and which would raise serum cholesterol, 1% is polyunsaturated, ~4% is conjugated linoleic acid (CLA), and the rest is either MUFA or is the saturated fatty acid (SFA) stearic acid that causes the same effect on total serum cholesterol (TSC) as MUFA (Keys et al. 1965; Grande et al. 1970; Bonanome and Grundy 1988; Tholstrup et al. 1994a, 1994b; de Roos et al. 2001; Mensink et al. 2003). By comparison, in butter from pasture-fed cows, 42% of the fat is CISFA (Couvreur et al. 2006) and would raise serum cholesterol despite butter having a total of more than 60% SFA.”
(FYI, butter also supplies twice as much cholesterol as tallow.)

Therefore, if the lipid hypothesis were true, we would expect butter and other forms of dairy fat (of which butter is merely the concentrate) to cause, or at least be associated with, more heart disease than meat fat, especially considering that most meat fat is less saturated than tallow.

To the contrary, the 2012 epidemiological analysis, Dietary intake of saturated fat by food source and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis, one of the few studies to separate saturated fats according to their dietary sources, found a strong protective (inverse) association between dairy fat and CVD, and a weaker positive association with the less saturated fat from meat, across a multi-ethnic population (this ruling out the possibility of the results being unduly influenced by genetic factors);

“When we evaluated risk across quintiles of SF consumption from each food source, a significant inverse association was seen for dairy SF [HR (95% CI) for extreme quintiles: 0.56 (0.38, 0.82); P-trend = 0.01], whereas meat SF was not statistically significantly associated with risk [HR (95% CI) for extreme quintiles: 1.40 (0.94, 2.08); P-trend = 0.12] (Figure 1). Butter and plant sources of SF were not associated with CVD risk, but ranges of SF consumption from these sources were quite narrow, which limited our ability to detect differences in risk across quintiles.”
“In sensitivity analyses in which angina was excluded from CVD endpoints, inverse associations of total, dairy, and plant SF with hard CVD were somewhat stronger, whereas the positive association of meat SF with hard CVD was slightly attenuated (data not shown).”

In case it is thought that the sample size in the MESA study (5,209) was too small, it is a common finding that dairy fat is either not, or is inversely, associated with CVD incidence.

An argument could be made that some factor associated with dairy fat, such as (hypothetically) calcium, reverses the harmful effect of saturated fat. If such were in fact the case, how nugatory would that harmfulness then need to be? Embedded image permalink

There may be things that raise cholesterol and that are associated with CVD. Industrial trans fatty acids seem to meet this case, as well as various organic toxins and heavy metals that are not fatty acids, and that are likely to be bad for you quite independently of any perturbations of your lipids. Sugar and high-GI starches are other potential candidates, which takes us into the intricacies of lipoprotein classes beyond the cartoon characters of cholesterol and LDL. There are also bound to be fatty acids, as well as other factors, which can increase CVD risk while lowering cholesterol. There have certainly been enough trials of cholesterol-lowering drugs, and cholesterol-lowering diets, where more people have died in the treated group, and sometimes died with lower cholesterol.

Yet people still believe this thing. It is nonsense. There are other things that better deserve the energy that has been poured into making people worry about saturated fat, and about the influence of dietary fats on cholesterol. The lipid hypothesis, and consequent pious attempts to respect or enforce the magical 10% saturated fat limit, have had a mischievous influence over the modern diet. Belief in it has not made us, in the majority, healthy, wealthy, or wise. It has made us saturate our bodies in polyunsaturated fats without considering whether they are omega 6 or omega 3, cis or trans, oxidised or unoxidised, or how far they are in fact necessary, or whether they bring anything in the way of nutrition to the diet to make up for the choline, carotenoids, cholesterol, retinol, menaquinone, and cholecalciferol we miss out on by not eating as much butter or fatty animal parts as our ancestors did. We have been fools, and we are making our society sick. It is time to stop.

      Hat tip to Nigel Kilburn for pulling up two studies from Siri-Tarino et al.’s 2010 saturated fat meta-analysis that did show correlations with heart disease. These were also the studies with the widest range of intakes. So what can they tell us?
      The first is by Jim Mann and colleagues from 1993, and straight up I am surprised that this has been included in any meta-analysis, because it uses a self-selected vegetarian cohort, with friends and family standing in for the rest of the population.
      “The study differs fromprevious prospective studies of diet and IHD in that the volunteers were individuals whose self-selected diet resembled, in nutrient content, current dietary recommendations rather than the relatively high saturated fat diet typical of most affluent societies. The ﬁndings may not only help to explain which attributes of a vegetarian diet protect against IHD but also which foods and nutrients are important in the aetiology of IHD in populations who modify their diets along the lines of present guidelines.”
      It’s odd that such high-bias methodology isn’t excluded from meta-analysis, and makes me wonder what else is included.
      What does Mann et al. tell us?
“Results—IHD mortality was less than half that expected from the experience reported for all of England and Wales. An increase in mortality for IHD was observed with increasing intakes of total and saturated animal fat and dietary cholesterol—death rate ratios in the third tertile compared with the ﬁrst tertile: 3.29, 95% conﬁdence interval (CI) 1.50 to 7.21; 2.77, 95% CI 1.25 to 6.13; 3.53, 95% CI 1.57 to 7.96, respectively. No protective effects were observed for dietary ﬁbre, ﬁsh or alcohol. Within the study, death rate ratios were increased among those in the upper half of the normal BMI range (22.5 to under 25) and those who were overweight (BMI over 25) compared with those with BMI 20 to under 22.5.
(Relative risk figures have been converted from 100 to 1.0)

      IHD was significantly associated with higher consumption of eggs, cholesterol, animal fat, and saturated fat.
      But, here’s the surprising finding; none of those dietary factors was associated with any increase in total mortality, significant or non-significant. People who avoided dying of IHD by following the healthy eating guidelines were dying at the same rate – the same ages - as their less health-conscious friends and family. This wasn’t pinned down to any particular cause of death.

      The fact that BMI under 20 was associated with as much increased risk of overall mortality as BMI over 25 (“total mortality was signiﬁcantly higher in those with an initial BMI under 20, and a similar though not statistically signiﬁcant trend is apparent for IHD mortality.”) wasn’t mentioned in the abstract, and is underplayed in the text (if it can be explained by undiagnosed pre-existing disease, so can the correlation with higher BMI). A bit like this dodgy AHF BMI calculator. Set this to BMI 7 (maximum height, minimum weight) and you still look healthy; muscular or curvy depending on gender. Results in real life may vary.

      The main dietary finding pertaining to all-cause mortality in Mann et al.;
“all cause mortality for all subjects was signiﬁcantly lower in the middle and highest intakes of green vegetables (0.62, 95% CI 0.46–0.83; and 0.74, 95% CI 0.56–0.99) and among those consuming the highest intake of nuts (0.76, 95% CI 0.60–0.97) compared with the lowest intakes of these foods.”

     The second paper is by Bonniface et al., and unfortunately doesn’t supply all-cause mortality data.
      “Not consuming alcohol, smoking, not exercising and being socially disadvantaged were related to high saturated fat intake and CHD death. Cox survival analyses adjusting for these factors found that a level of saturated fat 100 g per week higher corresponded to a relative risk for CHD death for men of 1.00 (0.86-1.18) and 1.40 (1.09-1.79) for women. This difference between the effects of saturated fat in men and women was statistically significant (P=0.019).”

     Mean intakes of SFA in Bonniface et al. - Men: 47.0 g/d Women: 34.4 g/d. A respectable ~20%E (similar to the consumption by Indians eating food prepared with ghee in Raheja et al. 1995).
“The cut-off points for the quintiles of saturated fat in grams per week were 220, 276, 337 and 427 for men and 159, 202, 252 and 319 for women. There was a clear trend to higher CHD death rates associated with higher total and saturated fats and Keys' fat difference in women.”

      Keys' fat difference? This is the ratio between SFA and PUFA.
      “The result for the Keys statistic indicates that a higher level of saturated fat can be compensated by a lower level of polyunsaturated fat, in the ratio 2:1.”
      PUFA by itself showed no correlations, but the Keys difference did. In fact, the correlation between Keys' difference and CHD in table 3 is pretty striking.

     Both populations were in Britain. Perhaps the take-home is, that in Britain, at least at a certain point in time, you could choose how you wanted to die to some extent by choosing your diet around heart guidelines. Or by watching your Keys' ratio if you were female (women today, with vegetable oil diets, would not have ideal Keys' ratios by these tables). But living longer than those around you by restricting saturated fat is not a prediction supported by this epidemiology, or by any meta-analysis, as was discussed by Simon Thornley, Grant Schofield and I in our letter to the NZMJ.

     Diet epidemiology is interesting stuff. It’s incredibly hard to do well, and the things we can take away from it are sometimes unexpected. The papers that go into meta-analyses, even for something like SFA, are wildly heterogeneous in design and in quality. Jim Mann et al.’s 1993 paper told me just about everything I wanted to know that it was possible to tell from the data collected. Bonniface et al. were more obscure; critical data points for the Keys' difference were not included. What use are quintiles without means or cut-offs?
      I was surprised, as I said, that the Mann et al. paper, good though it is, is being included in meta-analysis, because of the self-selection bias (so, self-selection in Paleo or LCHF diet studies shouldn't be a barrier to being taken seriously either). That it was included speaks to the impartiality of meta-studies like Siri-Tarino et al. 2010 that exculpate saturated fat. Meta-studies give the overall truth that is relevant for public health planning, but miss the finer details of what is happening in specific communities at specific times. For example:
      In Mann et al., nuts are protective. This is a common finding, e.g. in Hu et al. 1998. In Bonniface et al. PUFA is not associated with harm, but the Keys' difference is. In Britain at the time of this study, among the mainly middle and upper classes, perhaps vegetable oils were not in common use. Perhaps nuts were a major source of linoleic acid, enough to attenuate its relationship with disease. And in Bonniface et al., with its more working class catchment (and this being Britain, class distinctions do matter), perhaps the ideal Keys' difference of 2:1 is what you get closer to eating nuts and fish with meat and dairy fat, and the adverse lower and higher ratios are what you get either not eating nuts and fish, or using vegetable oils and spreads instead of animal fats.
(the mean PUFA intake of 63.1g/week for women is ~4%E).
Because it may turn out that when diet-heart epidemiologists one day separate PUFA in nuts and fish from PUFA in oils they will get very different values, as these AMD researchers did.

     Take home: For someone who has the disease of CHD, especially someone following a moderate fat, higher carbohydrate diet like most of the population (the dietary pattern at the heart of all epidemiology) it makes sense to follow these clues, as well as recognising the modern risk factors of sugar and refined flour; eat some nuts, fish, don’t eat red meat every day, eat only a few eggs per week, eat some full-fat dairy, and so on.
      On the other hand, for the average person to eat a pleasurable diet that has been designed around avoiding CHD risk factors from animal foods risks inviting in a host of other diseases that they may be susceptible to in ways they were never susceptible to CHD. Advice to the general population should be limited to recommending those protective factors for CHD that a) supply micronutrients, and b) are also protective factors in a wider sense (nuts, fish, fruit and vegetables, and full fat dairy), instead of messing with Keys' difference based on theories about blood lipids, as opposed to consistent findings based on real food inputs and hard endpoints.

This is just a short post to direct readers to my guest post here: http://profgrant.com/2014/07/30/all-that-fat-a-guide-for-the-perplexed/

Which contains all my thoughts about dietary fat recommendations and the lipid hypothesis, without too many distracting details.

I also want to supply a link to a most enjoyable book, Bertha M. Wood's "Foods of the Foreign-born in Relation to Health" from 1922.
https://archive.org/details/cu31924003579756
I think this is the first record of "dietary transitions", adverse changes to the traditional diets of migrants in a new land. It was written at the height of U.S. xenophobia (in the immediate aftermath of the Great War and the Bolshevik revolution) and can also be seen as a response to prejudice. Though the Hungarian child's diet below might not have helped much.

In 1922, diabetics were treated by restricting starch, especially from grains and legumes; this was replaced with non-starchy vegetables. Fat was not generally restricted (though this is said to be necessary in some cases, perhaps because sugar doesn't seem to have been reduced).
I learnt about Bertha M. Wood's book from The Old Foodie blog.

One of the arguments used by New Zealand's Public Health experts still opposed to LCHF and Paleo diets - opposed, that is to the idea of the more saturated animal fats being safe, either overall, or in a mainly wholefood, low carb context - is that low-fat dietary guidelines, and the decreased intake of butter, with increased use of margarine and seed oils, ought to be given some of the credit for a decreased rate of heart disease in the past 30 years.
They'll acknowledge that smoking cessation (to be fair, they had a bit to do with this too) accounts for some of the decrease.
But is that accounting for every factor likely to be significant? Most people who had heart attacks In New Zealand prior to 1984 went through the Great Depression, World War 2, and the 1951 Waterfront Strike. They had parents who lived through the 1919 influenza outbreak. Their lives were different in many ways from those of the generation dying early or living longer today.

One of those differences is environmental - the toxicity of industrial, urban, and rural environments has changed, mostly for the better; testing and legislation is mainly a product of 1970's environmental activism. And particulate vehicle emissions, to give the best-researched example, do seem to be causative of atherosclerosis. The last few decades have seen tighter and tighter restrictions on vehicle exhaust emissions on our roads and on the burning of fossil fuels and wood in private fireplaces in our cities.

Another change is genetic - in 1984, Wang was not the most common surname in Auckland. New Zealand has always had a small population, with a tendency for Kiwis to seek their fortunes offshore, and this loss has been offset and the population increased steadily through immigration, with the migrants' countries of origin altering over time.

Another change is in the micronutrient content of the diet. In early days, the poor were at more risk of deficiency diseases than they are today. Vitamins and minerals are added to junk food to give the advertisers something to boast about, and even to improve shelf life; the use of ascorbic acid as an antioxidant (E300-304) is no doubt a safeguard against scurvy in the least-well fed populations.

This change also applies to wholefoods - since the 80's, NZ's importation of foods - esp grains, legumes and fruit has increased, which means a wider spread of micronutrition. There is a wider variety of foods, and of ingredients; market deregulation since the 1980's means the New Zealand food environment has altered significantly.

See, for example Medsafe on selenium

The intake of selenium by New Zealanders has increased since the earlier Total Diet Surveys in 1982 and 1987/88. To prevent animal diseases, farm animals are drenched with selenium-enriched products and the meal fed to poultry has selenium added. Generally bread made in the South Island is lower in selenium than bread made in the North. Since deregulation of the grain industry much North Island bread has a significant proportion of imported, largely Australian wheat which is selenium-rich. But South Island bread is made predominantly with wheat grown locally in low-selenium soils. Current practices need to continue for the selenium intake of New Zealanders to remain around recommended levels.Meats, eggs, dairy products and bread are the main sources of selenium in New Zealand diets.⁶ Kidney, liver and seafood, and for the vegetarian, imported legumes are rich in selenium.

The relevance of this is that Finland - a seriously deficient country like NZ was 30 years ago - mandated selenium in fertilizer in the 1980s to reduce CVD incidence, raising serum Se levels within a short time.
Result? (or, correlation?)

Between 1982 and 1997, coronary heart disease mortality rates [in Finland] declined by 63%, with 373 fewer deaths in 1997 than expected from baseline mortality rates in 1982. Improved treatments explained approximately 23% of the mortality reduction, and risk factors explained some 53–72% of the reduction.
http://aje.oxfordjournals.org/content/162/8/764.full

This, of course, has been attributed to lipids and SFA too - selenium has been completely forgotten, it seems - but this was a huge, and brave, public health effort in Finland, comparable to iodised salt being introduced to iodine-deficient societies in the 1920s. And matched by what NZ has done, albeit by chance more than by design. Finland was one of Ancel Key's strongest statistical supports - and the methodologically questionable Finnish Mental Hospital Study is still a mainstay of lipid hypothesis epidemiology. We are not talking selenium supplementation above requirements, which doesn't prevent CVD, but correcting selenium deficiency. (If you ask me, the micronutrient theory of diet-health correlations is sadly neglected at present. What slows the oxidation of lipoproteins? Not so much any antioxidant tested separately at megadose intakes - just the whole antioxidant defense system working smoothly on a little bit of everything it needs. Selenium, zinc, etc., etc., etc.).
2014 is not just 1984 with less saturated fat.

There is more detail about the Finnish selenium programhere.

I bought this 45RPM record at a thrift shop the other day. Blue Band, by Bobongo Stars - the full version (it covers both sides) is pretty cool, with a great old-school synthesizer solo. The story of the song, and of Marsavco margarine is told here; it's a palm oil product (so not much need for hydrogenation), and today it's fortified with vitamins including nicotinamide; probably a good thing in the corn-eating regions of Africa. The song is credited to Marsavco-Zaire.

When this story broke, I had to look up amylin in my biochemistry (Mathews, Van Holde, Aherne 2000) and physiology (Best and Taylor, 1984) texbooks. Neither has amylin indexed. Nor do I remember any insightful blogs about amylin from the usual suspects recently. Flyin' blind here. Thank God for wikipedia.

This news story linking amylin build up to diabetes, based on new research conducted jointly in Auckland, New Zealand and Manchester England, makes the case reasonably clearly:

http://www.nzherald.co.nz/health/news/article.cfm?c_id=204&objectid=11313712

What does it mean?

Diabetes is defined as the loss of beta-cells, so that insulin production ceases - the insulin dependent stage. Interestingly, amylin allegedly plays the same role in type 1 and 2 diabetes, and the aggregates of amylin are amyloid formations similar to those seen in alzheimers. Before you start thinking of type 3 diabetes, though, the amyloids in Alzheimers aren't made of amylin. Amyloid just means "starch-like". What they have in common is beta-sheet protein structures (nothing to do with beta-cells) misfolding in a contagious, prion-like process.

What is amylin?

Amylin, AKA Islet Amyloid Polypeptide (IAPP) is a protein produced by beta-cells in tandem with insulin. Insulin promotes glucose uptake and metabolism in cells, amylin slows glucose - and other food - uptake from the gut, by delaying gastric emptying, and decreases appetite; it also seems to be responsible from the switch from muscle glycogenogenesis to adipose lipogenesis, so probably has a role in obesity. According to wiki the ratio is 100:1 in favour of amylin (unless I've read it wrong and it's the other way round). Is the ratio always constant? Does amylin have any independence from insulin? In any case, amylin plus glucose represents a two-pronged approach to preventing systemic over-exposure to glucose; insulin pulls glucose out of, amylin slows access into, the blood.

Some people think amylin should be included with injectible insulin for type 1 diabetics.

Amylin overproduction results in incompleted (proamylin, or proIAPP) molecules being retained in cells; these serve to promote crystalization of further amylin beta-sheets in the cell, the amyloid clumps then initiate apoptosis, killing of the beta-cells with eventual loss of insulin - and amylin - production.

This looks like the end-stage of hyperinsulinaemia; this over-production of amylin (and insulin) is being driven by excess glucose intake, the amylin incompletion and insulin resistance may also indicate an overall micronutrient deficiency, and the out-of-phase insulin response to begin with indicates a) salivary amylase polymorphism, b) presence of excess omega 6 -> PGE2, c) absence of factors inhibiting PGE2, e.g. omega 3, CLA (the most likely reason for the diabetes-protective effect of dairy fat, or, if you don't eat dairy, ruminant fats).
Note that PGE2, an omega 6 series prostaglandin, inhibits glucose uptake, and to a somewhat lesser extent fructose, in sheep, but increases it in rats - probably the better model for human response. If this is the case, PGE2 is increasing glucose uptake as it decreases first phase insulin response, which is already diminished in individuals with fewer salivary amylase gene copies. The compensatory rise in second phase insulin response - exacerbated by 12-HETE, an omega 6 series eicosanoid - results in a larger area under the curve for both glucose and insulin; i.e., in hyperglycaemia and hyperinsulinaemia.

It is interesting that this hyperinsulinaemia-related problem with amylin is also causative in type 1 diabetes. It means that lower carb diets can be recommended to those at risk of this disease.
The T1D connection is really interesting. .I have a friend who is T1 diabetic; he said when he was 12 he got a craving to eat dry Milo (Nestles chocolate flavoured drink sweetened with maltose, i.e. glucose), ate a big tin of it in one day, crashed into a coma and woke up in hospital on insulin. That seems to show pronounced hyperinsulinaemia immediately preceding beta-cell burn out. Perhaps a combination of sudden hyperinsulinaemia from an inflammatory, infective, or autoimmune cause together with a low tolerance for amylin production.

Both insulin and amylin contain disulfide bridges (Cys-S-S-Cys) and this is interesting as the bridges are only meant to form outside the cell (the peptide is expressed as a string from the reducing environment of the cell, where the cysteine residues exist as 2x Cys-S-H, into the more oxidising serum enviroment, where the sulfur bonds snap together as the cysteine residues are oxidised to Cys-S-S-Cys plus H2O). If insulin output is very high, this puts a heavy demand on the reducing systems of the cell; glutathione, glutathione reductase, thioredoxin reductase and so on. Hydrogen sulfide - H2S - is also protective in the beta-cell for some reason. These are mostly selenocysteine enzymes, and selenocysteine is also required for a protein folding enzyme. (note though, supplying 200mcg Se as selenomethionine in America, not overall a selenium deficient country, has been associated with double the rate of diabetes in one study that was not directed at glycemic endpoints).

Selenoprotein S

Selenoprotein S is involved in retrotranslocation of misfolded proteins from the endoplasmic reticulum to the cytosol. This protein may also be involved in inflammatory and immune responses

Here is the Wiki page on amylin. It's interesting, has the background to the latest research, and I wonder why we never hear about this hormone in diet-health discussions? I guess that from now on we will be hearing more of it.
http://en.wikipedia.org/wiki/Amylin

The take home - keep insulin production under control by counting carbs and avoiding vegetable seed oils, and amylin should tag right along, ensuring beta-cell function lasts a lifetime.

A nicely controversial new paper from the American Heart Association, in which linoleic acid in plasma phospholipids is the only PUFA with negative correlation with total mortality. The more LA n-6 in the membranes of your red and white blood cells, together with your lipoproteins, the longer you live. So should we switch back from butter to margarine?
(tl;dr; if you really care eat some nuts, nuts are the only LA source convincingly associated with reduced mortality, although nuts also being associated with exercise, wealth, not smoking and other markers of virtue, it's hard to be sure, but this latest research does help the nut case).
Here's the abstract

Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality: The Cardiovascular Health Study

Background—While omega-6 polyunsaturated fatty acids(n-6 PUFA) have been recommended to reduce CHD, controversy remains about benefits vs. harms, including concerns over theorized pro-inflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid(LA, the major dietary PUFA), γ-linolenic acid(GLA), dihomo-γ-linolenic acid(DGLA), and arachidonic acid(AA),with total and cause-specific mortality in the Cardiovascular Health Study, a community-based US cohort.

Methods and Results—Among 2,792 participants(age≥65y) free of CVD at baseline, plasma phospholipid n-6 PUFAwere measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34,291 person-years of follow-up (1992-2010), 1,994 deaths occurred (678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher LA was associated with lower total mortality, with extreme-quintile HR=0.87 (P-trend=0.005). Lower death was largely attributable to CVD causes, especially nonarrhythmic CHD mortality (HR=0.51, 95%CI=0.32-0.82, P-trend=0.001). Circulating GLA, DGLA, and AA were not significantly associated with total or cause-specific mortality; e.g., for AA and CHD death, the extreme-quintile HR was 0.97 (95%CI=0.70-1.34, P-trend=0.87). Evaluated semi-parametrically, LA showed graded inverse associations with total mortality (P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both.

Conclusions—High circulating LA, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults.

You'll notice the name of Dariush Mozzafarian as senior author (he's from the U.S. but the research was done in Sydney, Australia, so it's unlikely he supervised it in person). Mozaffarian is open-minded about saturated fat and low-carb diets and has played a major role in rehabilitating dairy fat, which ought to lay to rest conspiracy theories about the study (publication bias might be another question). The result makes sense to me.
Remember that these are plasma phospholipids, that is, they exist in the oxidising environment of human blood. We make use of this dual state system of redox balance; antioxidant enzymes and glutathione keep the intracellular balance in favour of reduction, and the non-enzymatic reactions inevitable in the anarchic extracellular environment, and the relative lack of extracellular antioxidant enzymes, reverse that, so that insulin and amylin molecules and immunoglubulins adopt their active, oxidised structures only after exiting cells, and ascorbic acid is oxidised to dehydroascorbic acid before being taken up and regenerated - reduced - inside cells.
Everyone knows what happens if this balance is lost either way; reductive stress limits the cell's ability to perform metabolic functions, oxidative stress degrades cellular structures and closes them down.

Cardiolipin - the 4 radicals are predominantly C18:2, linoleate.

Linoelic acid is a major determinant of cellular health, because it's incorporated into a phospholipid called cardiolipin, which sits in mitochondrial membranes; the linoleate is essential precisely because it's the most easily oxidisable PUFA in living systems. When cardiolipin oxidises faster than glutathione and its enzymes can repair it, it's time to close that mitochondrion and start another - in this way, inefficient mitochondria that spew free radicals aren't kept alive forever. This isn't the only function of cardiolipin, but canary in the metabolic coalmine is a pretty useful job.

Cardiolipin radicals

Therefore it seems to me that the presence of higher levels of LA in plasma phospholipids, in an oxidising environment, is not a mere indication of its dietary ingestion, but rather a marker of the antioxidant status of the blood and of the lipoproteins, which carry carotenoids, coQ10, retinol, tocopherol and other lipid antioxidants to and from cells. This explains why nut consumption is inversely associated with mortality, but overall LA consumption is not (if it was, the authors of this study would have mentioned it - senior author Hu is the nut guy).
It would be pretty hard to have a less than adequate LA intake on a high-fat paleo diet, as I discussed here.

Another process destructive of plasma phospholipid LA is inflammation; the conversion of arachidonic acid to prostaglandins and eicosanoids. Because AA itself is essential and conserved in the cell membrane, there is a flux through AA, with a constant replacement from LA. And guess what? Plasma phospholipid PUFAs, including LA, are preserved on very low carb diets - one of the anti-inflammatory benefits.

In other words, the paper under discussion seems to support the good, old-fashioned, free radical theory of disease and ageing, as well as the inflammatory theory of CHD. It doesn't support the intake of high levels of high LA seed oils, because what is going to happen to that LA? Almost all of it is going to be oxidised in the liver, with 22% of the acetyl-CoA produced going to make cholesterol.
You heard me - linoleic acid has the opposite effect from statins, increasing hepatic cholesterol synthesis. It also increases hepatic LDL receptors and pulls cholesterol in from the blood stream. Sometimes too much cholesterol, because all this free cholesterol oxidises easily, and when it does, cardiolipin also oxidises and mitochondria die (all this is referenced in my NASH series, see the Labels sidebar). Statins, if you overlook the side effects, are probably anti-inflammatory; I don't think there's much chance that seed-oils are.

Those of my readers from outside New Zealand might be interested in this local story. Especially you Australians.

It starts here:
Katherine Rich, a former National party MP, now the chief executive of the New Zealand Food and Grocery Council, an industry lobby group, is on the advisory board responsible for the health star rating system. For some reason the N.Z. Government takes the position that we can only counter diet-related ill health by paying the food industry to do something about it on their own terms.

This kind of assumes some basic honesty and interest in science on their part. Instead, we get this:

Embedded image permalink

Katherine Rich, in her role as pretend responsible person working with government (and presumably collecting pay for that), can't attack the anti-sugar lobby as virulently as she'd like, so hires blogger Cameron Slater (wide following, no morals) to do it for her.

Meanwhile, she's on the board overseeing the Health Star food labeling system, which is more industry reps (Unilever, Nestles, etc.) than scientists. As wikipedia says:

Emails leaked to political writer Nicky Hager claim that Rich, in her role as Chief Executive of the Food and Grocery Council, has while on the board of the Health Promotion Agency (a Crown entity) fed prominent blogger, Cameron Slater, with posts that denigrate individuals in academia and the media who report on news or support health initiatives inimical to the interests of the food, alcohol, tobacco and soft drink industries. The posts have been published as if by Slater himself on his blog Whale Oil Beef Hooked as recently as February 2014.
Here is Whale Oil's "soft drink" archive, if you want to see what your tax dollars have been paying for. These are the people our government thinks it can work with.
Actually, Slater is someone the National Government already works with; the bigger fish of the Whale Oil saga are the Prime Minister (or his office, no-one's sure how much he even knows what's going on), and the Justice Minister, Slater's closest friend in power, who has already fallen on her sword. The Katherine Rich Health Star business is a minor part of the scandal to most people.
Here's what she paid Slater to say about the soda tax:

dpoll

The question is rather clumsy. Imagine the result if they had asked “Do you think it is a good idea to tax ALL Kiwis with a sugar tax, increasing food and drink prices across the board, when it is only fat bastards who should be taxed?”.

These are the people our government puts in charge of your health when you shop.
Blogger the Jackal has the wider story and a link to the emails here.
Direct download here: http://wikisend.com/download/519750/Katherine%20Rich.zip

Slater is in the tradition of the scurrilous and venal Restoration pamphleteer, selling spicy stories about the enemies of his patrons. He's kind of admirable in his whole-hearted and public commitment to turpitude. And sometimes the Slater/Graham/Rich hydra comes up with lines like:

So long as the health nazis promote the food pyramid that is heavy on carbohydrates and low on proteins then we will continue to get fatter, especially if we don't exercise to burn those calorie loadings. Taxing sugars and fats won’t work.

Nice try, but it still doesn't buy my trust.
P.S. Katherine Rich is also on the Health Promotion Agency board. This is more balanced than the Health Star food labeling board, on the HPA board Rich is the only industry rep. And AUT's own Grant Schofield is on the HPA board. Should make for interesting meetings.

John Yudkin on Dietary Instinct, plus examples from experiments with Wistar Rats and Orphans

Does reductive stress drive an adaptive inflammatory response, in depression linked to diet and lifestyle?

The authors hypothesize that the increased PMRS in erythrocytes during aging may be a protective mechanism of the system for efficient extracellular DHA reduction and ascorbate recycling under condition of increased oxidative stress.

And, perhaps, increased cycling of ascorbate is also a response to reductive stress. Oxidative stress, when not adaptive, as in the immune response, or toxic in nature, is the product of reductive stress, and both are increased by hypercaloric intakes of micronutrient deficient diets.

Does Aspirin Prevent Liver Cancer, and, Does Ginkgo Extract Cause It?

Meta-Analysis of Multiple Primary Prevention Trials of Cardiovascular Events Using Aspirin

Nonsteroidal Anti-inflammatory Drug Use, Chronic Liver Disease, and Hepatocellular Carcinoma

Minimum Pricing of Discretionary Calories as a Potential Government Intervention.

Magnus Pyke on energy intake, plus Jack Drummond and Wartime Rationing

A Request for Hep C Epidemiologists to Pay More Attention to Linoleic Acid Intakes

On Participating in a Phase III Trial of Sofosbuvir and GS-5816 for Hepatitis C

On What I Eat These Days

AUT's Submission on Proposed "Changes" to New Zealand's Dietary Guidelines

Saturated fat IS good for you, but how much polyunsaturated fat do you need?

Uffe Ravnskov, Zoe Harcombe and Aseem Malhotra on the New Censorship

Diabetes as an Iatrogenic Disease - the Indian Experience

Diabetes as an Iatrogenic Disease - the Second Hit

Refined grain consumption and the metabolic syndrome in urban Asian Indians (Chennai Urban Rural Epidemiology Study 57).

Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not β-cell function in humans.

Another Reason why the Lipid Hypothesis is Bunk

Epidemiology can be Interesting

A Guest Post on Prof. Grant Schofield's Blog

The Difficulty of Attributing Ends to Means - Selenium and Heart Disease

Amylin - the "root cause" of diabetes?

Plasma phospholipid linoleic acid is a marker of health.

Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality: The Cardiovascular Health Study

Who put the Fox in charge of the Henhouse? Dirty Politics contaminates the food supply.