Doctors Respond to the Sydney Diet Heart Study

(music - Christmas in the Country, The Puddle)

“The results show that the omega-6 linoleic acid group had a higher risk of death from all causes, as well as from cardiovascular disease and coronary heart disease, compared with the control group.”

We should be most skeptical of the research that best confirms our own beliefs. It may not contain an inaccurate result – in the case of the Sidney Diet Heart Study, the result is consistent with the totality of the evidence that is appearing from other sources – but it may not be as convincing to others as it appears to us. We should always be alert to the desirability of designing experiments to produce results that, one way or the other, will convince any reasonable person. In diet studies this may well be unattainable, and usually the “expert evidence” of clinical studies has to be considered in the context of circumstantial and eyewitness evidence from other sources, but it is the scientific ideal.

On the BMJ website where the study appears, doctors can send in their responses, and some of these responses give cogent reasons why a reasonable person, especially one not engaged with the Paleo discussion of seed oils over the past few years, might remain unconvinced by the latest revelations.

Perhaps the best response comes from Professor Jean Gutierrez, assistant professor of exercise science at Washington University. She points out that one of the products used in the trial probably contained high levels of trans fats:

Participants in the intervention group consumed “Miracle” Margarine, a product based on safflower oil. Hydrogenation of safflower oil itself creates a grainy product low in linoleic acid, so high-linoleic safflower oil margarine products were created by blending liquid safflower oil with another hydrogenated oil stock (3). Miracle Margarine used in the original study was either low in linoleic acid (due to hydrogenation of the safflower oil itself) or the oil was blended with another commercially hydrogenated fat to create a plastic margarine product. An investigation by Bernfeld, Homburger, & Kelley, published in 1962, indicated that the fatty acid composition of most margarines of the time were about 50-60% 18:1 monounsaturated fats (including oleic and trans isomers) and about 20-30% 18:2 linoleic acid, even in those products having high-PUFA claims on the label (4). None of the 22 margarines studied had a majority of fatty acids coming from PUFA. Another report from the same time period indicates that commercially produced hydrogenated fats, like those added to safflower oil to make margarine, were generally composed of about 25-40% trans fats (5). Fatty acid composition of margarines in the 1960s investigation were not comparable to liquid vegetable oil, despite package claims. The only reference supporting the healthful content of Miracle Margarine is a very general press release from the company who made the product (6). It is probable that Miracle Margarine had significant trans fatty acid content.

This is an obvious confounder, hard to dispute on science grounds. Morally it might not make much difference; if advice to reduce saturated fat and increase PUFA consumption lead to the use of such dodgy products such as Miracle Margarine, as it did, then it still stands condemned historically. Have there been studies where oil but not margarine was the intervention? Was the Rose Corn Oil Study really just a study of corn oil? Comments section please.

In the section "other dietary considerations" it appears that the "prudent diet" intervention group avoided the ordinary margarines allowed in the diet of the controls. We will probably never know which group ate most trans fats. The fact that the intervention group had low cholesterol and trans fats are supposed to elevate LDL cholesterol does seem to indicate that any harm trans fats may have done was not due to "lipid hypothesis" mechanisms.

Having established her scientific objectivity by drawing attention to the study’s biggest flaw, Professor Gutierrez strikes a home run with her last paragraph:

In addition to increasing PUFA intake, participants in the intervention group reported reduced dietary saturated fat, cholesterol, and calorie intake from baseline. A negative energy balance was verified with a slight mean drop in BMI. As expected, circulating total cholesterol and triglycerides were reduced in the intervention group, but mortality outcomes were not improved consequent to these circulating lipid and anthropometric changes, which is unexpected and interesting. The more important question arising from this study may be why a dietary intervention that improved all of these commonly used surrogate end points did not reduce all-cause mortality?

Why indeed, the world wonders.

Surgeon Basil D Fadipe from Dominica has an explanation for the result:

In a nutshell, the study shows LA is a 'substrate' for oxidative stress convertible to toxic derivatives, mechanistically adverse to the cardiovascular-coronary integrity; An otherwise good dietary item, LA's bad company (smoke/alcohol) wrecks its good potential.

This view has some merit – LA plus alcohol is definitely destructive to the liver via these mechanisms, and there are clearly links between high alcohol consumption and the negative effect of LA in the study (though it doesn't seem that abstinence removes the risk), but it does seem like special pleading. People will be exposed to oxidative stress in various ways, not all easily predicted or avoided. Why consume a dietary item that magnifies this insult in quantities greater than those required for essential functioning?

UK GP William K. Neville sums up the Paleo view;

Linoleic acid is an omega 6 fatty acid. It causes weight gain and inflammation. Omega 3 fats have the opposite effect. The ideal ratio of omega 6 to omega 3 in the diet is about 2:1 [9]. Modern diets have a ratio of 20:1 due to the false belief that linoleic acid is good for us. In pre-historic times weight gain from eating omega 6 fats in nuts and seeds, which were plentiful in the autumn, was an advantage to prepare humans for winter [10]. Meat from grass fed animals has a good amount of omega 3. But 99% of farmed animals are fattened on grain products such as brewery waste prior to slaughter which lowers their omega 3 levels to zero and the meat contains only omega 6. Similarly, farmed fish has reduced omega 3 levels due to being fed on grains.

Heart disease was rare before the introduction of industrial seed oils at the start of the 20th century [11]. Four meta-analyses recently prove saturated fat to be harmless [12]. The lesson of this article is that it is time we stopped demonising the really healthy fats such as butter, lard, beef dripping, coconut oil and palm oil [13, 14].

He makes more of the case against dairy than is perhaps justified by the evidence to date when he says:

The most important oxidising agent of LDL particles is the peptide BCM-7 produced by the digestion of A1 milk. The level of A1 milk consumption in countries is directly proportional to the rate of heart disease. Milk in the UK is mostly A1. Milk in Africa is mostly A2. France is in between. A few supermarkets have recently begun to sell A2 milk which has the potential to prevent many diseases such as type 1 diabetes and heart disease [6, 7, 8].

All I can say is that A2 milk tastes better, but is just as allergenic for my purposes. Milk is a complex food and there is no one factor that applies to everyone, but the BCM7 case outlined in “The Devil in the Milk” deserves study. I expect there are many other things that correlate with heart disease just as well as A1 milk does. Consider though, that when you eat meat, you eat from one or maybe two animals (unless it’s processed sausage meat). When you drink milk, the milk from large numbers of animals has been combined, each with its distinctive immunological factors. Our milk-drinking ancestors, if we had them, probably drank from one or two cows at a time. My granddad used to say that one secret of health was not to mix one’s drinks.

American Physician Megan I. Maurer makes a valid point that will also appeal to Paleo dieters:

I would like to point out that the source of the omega-6 fatty acids in this case was from safflower oil and safflower oil margarines which, despite being high in omega-6 fatty acids are still very calorically dense and in my opinion are not representative of what you might see had they used a whole food course of omega-6 fatty acids, such as sunflower kernels or walnuts. It has been consistently shown that a whole-food plant-based diet offers great cardiovascular protection. I think a study showing increased intake of omega-6 fatty acids in their whole form vs. saturated fats would have been more telling than just replacing it with oil.

Of course a diet of walnuts (an omega-3 nut, in fact) and sunflower seeds will introduce other confounders. But a worthwhile experiment would be to replace fatty meats with nuts and seeds, and butter and cooking fats with spreads and oils. The difference between intrinsic and extrinsic fats may be as important a confounder as the difference between intrinsic and extrinsic sugars.



The question is, more studies are needed, but are they ethically justified? It’s easy to test a dietary change when the evidence one has seen and the theories that seem to make most sense suggest it’ll be beneficial. Is it right to continue to experiment in this way as the evidence of harm accrues?
You might suspect it was the trans fats in the margarine that caused those extra deaths, but would you be prepared to re-run the study without them to find out?

However, the fact is that the experiment has overtaken our society and most of us have been enrolled in it, despite the actual results from the Sidney Diet Heart Study proper having been “lost” since 1973.

If PUFAS do have some potential for good instead of evil in certain cases, can we avoid discarding the baby with the bathwater? In 2009 Stephan Guyenet analysed a 1994 study that compared the so-called “prudent diet” used in Sydney with a diet that supplied limited omega-6 in the context of adequate omega-3; the LyonDiet Heart Trial. He writes:

Here's where it gets interesting. The intervention group ate three times as much omega-3 alpha-linolenic acid as the control group, and 32% less omega-6 linoleic acid. The ratio was 20 : 1 linoleic acid : alpha-linoleic acid in the control group, and 4.4 : 1 in the intervention group. This was due to the combination of a low-fat diet and the canola oil goop they were provided free of charge. 

But it gets even better. The intervention group reduced their omega-6 linoleic acid intake to 3.6% of calories, below the critical threshold of 4%. As I described in my recent post on eicosanoid signaling, reducing linoleic acid to below 4% of calories inhibits inflammation, while increasing it more after it has already exceeded 4% has very little effect if omega-3 is kept low*. This is a very important point: the intervention group didn't just increase omega-3. They decreased omega-6 to below 4% of calories. That's what sets the Lyon Diet-Heart trial apart from all the other failed diet trials. 

After five years on their respective diets, 3.4% of the control (prudent diet) group and 1.3% of the intervention ("Mediterranean") group had died, a 70% reduction in deaths. Cardiovascular deaths were reduced by 76%. Stroke, angina, pulmonary embolism and heart failure were also much lower in the intervention group. A stunning victory for this Mediterranean-inspired diet, and a crushing defeat for the prudent diet! 

There's a little gem buried in this study that I believe is the other reason it didn't get accepted to the New England Journal of Medicine: there was no difference in total cholesterol or LDL values between the control and experimental groups. The American scientific consensus was so cholesterol-centric that it couldn't accept the possibility that an intervention had reduced heart attack mortality without reducing LDL. The paper was accepted to the British journal The Lancet, another well-respected medical journal. 

[implications of the study here]

So in both the Sydney study and the Lyon trial, total cholesterol and LDL cholesterol had nothing to do with whether participants lived, or died of heart disease. Of course the Lyons “Mediterranean” diet only outperformed the “prudent” diet; the controls in the Sidney Diet Heart Study already seem to have done that by eating as people normally did in Sidney between 1966 and 1973.

The last word goes to Professor Dhastagir S. Sherrif of Benghazi University, Lybia:

Polyunsaturated fatty acids (PUFA) are essential fatty acids to be supplied in the diet. These are important for membrane function, producing eicosanoids; the endocannabinoids, the lipoxins and resolvins form lipid rafts for cellular signaling, act on DNA, activating or inhibiting transcription factors such as NF-κB - playing a vital role in physiological functions of the body. Yet there needs to be a balance between its intake and the form of PUFA taken in the diet.

Being polyunsaturated, they generate free radicals, cause lipid peroxidation and damage mitochondrial function. It is suggested that the intake of PUFA must be accompanied by adequate amounts of intake of anti-oxidants such as vitamin E. Human body and its metabolism cannot be viewed as parts but as whole body metabolism. Whole body metabolism needs to be viewed with the interplay of internal and external factors that regulate and maintain homeostasis. Extracellular factors including the dietary constituents need to be balanced with the internal physiological milieu unique to every individual. We need to remember the Daedalus effect: for every remedy there is an adverse side effect. How we balance them is the duty of true science that will help promote health.

(photos by Hayley Theyers (c) 2013)

When “Healthy Eating” Becomes Police Business

We’ve had a wonderful summer in New Zealand, with one of the driest Januaries on record. So we Kiwis get out to the beaches as much as we can, soaking up the life-giving rays of the sun and marinating in the surf. 

Music: Forever Changes by Love (opens in new window). 

We usually drive to get any great distance; in fact we’re high in the stats for vehicle ownership thanks to our acceptance of cheap, excellent quality, second hand Japanese car imports. Consequently the roads get a bit busy and, now and then, unsafe on holidays.

Last Monday was Anniversary Day, and I was driving back to Auckland after enjoying sun and surf at Papamoa near Tauranga. The weather was hot, the road still not so busy, as I cleared the Karangahake Gorge and headed into Paeroa. Suddenly, I found myself in a thick stream of traffic that had slowed to a crawl on the outskirts of Paeroa.

[Digression, for entertainment purposes only. Note the Boer War memorial, the rock on a plinth in the upper right corner. This monument bears two plaques; one to commemorate the consecration of the monument on the date of the coronation of King Edward VII, the other, of equal size, to advise that the coronation was in fact delayed due to illness and to correct the information on the first plaque. Obviously didn't have Twitter in those days. Edward was operated on for appendicitis by Sir Frederick Treves of Elephant Man fame, assisted by Joseph Lister, and made a full recovery. Apropos of the King, as wikipedia states in its inimitable house style:
"The tradition of men not buttoning the bottom button of waistcoats is said to be linked to Edward, who supposedly left his undone due to his large girth.^[9] His waist measured 48 inches (122 cm) shortly before his coronation.^[44] He introduced the practice of eating roast beef, roast potatoes, horseradish sauce and yorkshire pudding on Sundays, which remains a staple British favourite for Sunday lunch."]

To continue:
Some minutes later we could see the cause of this obstruction: a police checkpoint. This would normally be expected to relate to testing for alcohol, or checking vehicles and warrants of fitness for roadworthiness, or investigating a recent crime. Police business. 

My car was waved over and stopped. With the clear sense of innocence that comes from imperfect recall, I wound down my window and listened to the police officer.
A campaign against driver fatigue; would we like a bottle of water for each person in the car, and a leaflet on avoiding fatigue? Yes please, and I drive off.

Later I looked at this leaflet. (pdf download). Tips for healthy eating, published by the Accident Compensation Corporation in 2007.

In other words, the New Zealand Police were detaining motorists to give them a leaflet printed by another arm of government, the ACC, that contained “healthy eating” propaganda information that is usually the responsibility of the Ministry of Health. Very interesting.

Now let me just say straight out, I don’t have a problem with the Police doing this. Anything that makes their presence felt on the roads on these holiday weekends reduces the crash rates (I don’t believe there were any serious crashes between Paeroa and Auckland that day), the water was a welcome gift for many, they would be able to weed out really intoxicated drivers or unsafe vehicles or loads through the checkpoint if such appeared, and the “softly softly” approach to policing is good for public relations.

Nor do I have too much of a problem with the leaflet. The “healthy choices” specified are generally more nutritious than the foods they are meant to replace, and even if the message has an anti-fat bias, the fat you’ll find in a donut isn’t its saving grace. My own breakfast that day was fried bacon, eggs, black pudding and tomatoes, and I stayed alert and didn’t get “so hungry” or eat at all till dinner time; which is a contrast to how I used to feel driving long distances on the old “healthy” diet – tired and hungry and somewhat sick.

What interested me most was the sole “scientific” claim in the leaflet.

“A study of a truck fleet showed that the number of serious crashes soared half an hour after the drivers ate fatty or sugary foods”

No reference given. My God, I thought, what truck fleet has so many serious crashes that these sorts of statistics are able to be generated? Whatever they eat, this company sounds like a public menace.
On the face of it, there are other flaws in the argument; most accidents involving trucks are not the trucker’s fault, and there are increased accident rates at certain times of day, due to circadian factors, which may coincide with meals. Did they separate sugar from fat, from starch, from total calories?
The study is mentioned online in terms suspiciously similar to those in the leaflet, but never referenced, and seems to be immune to my normally productive search style. I am only able to learn that it took place in the UK.

This called for a phone call to ACC, then an email to their statistics department, which received a prompt acknowledgement and began a wait for information. Meanwhile, I checked out references to driving safety in David Benton’s “Food for Thought”. Too much or too little blood glucose is associated with accidents. Lowered cholesterol levels (by drug or diet) are associated with a doubled risk of death by vehicle accident, homicide, or suicide (pdf), probably due to increased aggression (I suspect this might not be the case if increased fish consumption caused the drop, but only if it was due to polyunsaturated seed oils, or statins and other drugs).

This would seem to contradict the message in the leaflet if the first part of the lipid hypothesis were to actually be true (I suspect that cholesterol and diet are not so predictably linked at the individual level).

Less fatigue in the short term perhaps, but more aggression and self-harm on our roads as healthy eating works its dark magic over time.

My advice for safe driving would be to avoid foods that cause blood sugar slumps (refined starch and sugar), skip anything deep fried, go for a little protein (cold meat, smoked fish, boiled eggs, cheese), raw vegetables and fresh fruit if you’re hungry on the road. Eat a filling breakfast like I did but otherwise don’t fill’er’up till you get where you're going. Drink plenty of water, if for no other reason than to make you stop and stretch your legs whenever you pass a toilet. Drink coffee, black or with cream, rather than uber-sweet energy drinks, but not too much too soon . And, over the longer haul, unless you are under the care of a competent cardiologist for good and proper reasons (perhaps time to reconsider whether you should be driving precious or heavy loads on long trips at all), avoid the temptation to tamper with your “cholesterol”. That’s a form of self-abuse with the potential to lead to mental and physical degeneration.

Look, I’m no Zoe Harcombe. I’m not even very good at math, so I’m not going to wait till the study arrives and post the analysis that’s been lacking, I’m just going to post this review of the leaflet. When the study turns up, I’ll link it and discuss it in the comments section of this post. The thing I find interesting here is the insight into how government departments turn epidemiology into action (or, perhaps, how they select epidemiology that supports actions decided on for other reasons). As I said, I don’t have much of a beef with the pamphlet itself (except for the sloppy citation).

Pyridoxine – Toxicity and Deficiency, and the balance between B6 and protein.

You could make an argument that the pyridoxine form of vitamin B6 is the only really dangerous vitamin supplement. Overdosing on anything else is unlikely if you stick to recommendations, but pyridoxine neuropathy is insidious and persistent and may happen at intakes as low as 200mg/day, and quite possibly lower (case history reporting neuropathy from 100mg/day taken for 10 years).

Axonal pathology is also a feature of the neuronopathies, toxic states in which the primary injuries are found in neuronal cell bodies. This is exemplified by pyridoxine neurotoxicity, where there is sublethal or lethal damage to larger cytons in the sensory ganglia, with failure of such neurons to maintain their axons.

In this brilliant study, the 5 volunteers were the study authors: a detectable neuropathy was induced by a 12mg/Kg/d dosage after 7 months.
However, other factors can increase sensitivity, especially protein deficiency.

Large doses of pyridoxine cause injury to the primary sensory neurons in trigeminal and dorsal root ganglia of animals and patients subjected to megavitamin therapy. The increased hazard to subjects with reduced renal excretory function has been explored previously. In the present work, the neurotoxicity of pyridoxine for rats was found to be increased by dietary protein deficiency. A mere 3 or 7 days of pretreatment with either of two protein-deficient diets were sufficient to accelerate and intensify the clinical neurological signs and histological lesions from pyridoxine injections. These results are caused, at least in part, by loss of body weight, decreased protein binding in serum and decreased consumption of water and decreased volume of urine, which reduce the urinary losses of the toxicant. The vitamers related to pyridoxine (pyridoxal, pyridoxamine) and the coenzyme (pyridoxal 5-phosphate) did not cause clinical signs or lesions similar to those produced by pyridoxine even when injected in maximum tolerated doses. Neither a protein-deficient diet nor bilateral nephrectomy changed the results with the vitamers.

Note that the vitamers (the animal forms of pyridoxine) and the co-enzyme P-5-P (PLP) were not toxic.

I strongly recommend using only vitamin supplements that contain P-5-P or one of the vitamers. A much lower dose can be effective if P-5-P replaces pyridoxine.

The relationship of B6 to protein is important because P-5-P is the coenzyme for most reactions involving amino acid metabolism or catabolism. To make niacin from tryptophan, nitric oxide from arginine, serotinon from tryptophan, cysteine from methionine via homocysteine, these and many more reactions of that type all require P-5-P. It is also required for glycogenolysis and phospholipid synthesis.

Meat, fatty fish, potatoes and bananas are all good B6 sources, but processed meat can be very low in B6 relative to how much protein it supplies. Low B6 status is one of the more common deficiencies detected when populations are studied. Could this be one of the reasons there is always an epidemiological difference between red meat and processed meat? Or could it just be that people who eat processed meats tend to have a greater appetite for, or tolerance of, processed rubbish in general?

The activation of pyridoxine to P-5-P requires riboflavin and magnesium, and deficiencies of these 2 nutrients, deficiencies which are in all conscience common enough (B2 is easily destroyed by UV light) could in theory also sensitize one to pyridoxine toxicity.

There are many features of amino acid metabolism in cirrhosis that suggest that activation of dietary pyridoxine to P-5-P by liver has become inadequate, and/or that the breakdown of P-5-P is excessive.
After administration of pyridoxine there was a significant increase in the plasma PLP level over a 2- to 12-hr period, after which the concentration returned gradually toward the initial value. The area under the concentration/time curve was from 2 to 8 times smaller (P less than 0.002) in the patients with liver disease. To assess possible mechanisms of this change, 5 mg of PLP were intravenously administered to the various patient groups and the pharmacokinetics of the disposition were assessed. The initial and steady state volumes of distribution of PLP were comparable in cirrhotics and controls (P greater than 0.05), but the clearance of plasma PLP in cirrhotics was much faster (63.0 +/- 7.4 versus 31.7 +/- 2.7 ml per min, P less than 0.004). Similar findings were obtained in the other liver disease subjects

There is an inverse association between dietary B6 and deep vein thrombosis.

Our study indicates that low vitamin B6 is associated with an increased risk of recurrent VTE. Until recently, the thrombotic risk associated with low vitamin status was entirely attributed to impaired homocysteine metabolism. But since doubts have been raised about the causal role of homocysteine in thrombotic disease,⁴ other functions of B vitamins need to be considered. Vitamin B6 is a co-enzyme in the metabolism of aminoacids, carbohydrates, neuro-transmitters and lipids,¹² and administration of vitamin B6 inhibits platelet function.¹³ Low vitamin B6 has also been related to elevated C-reactive protein levels and other markers of inflammation,¹⁴,¹⁵. In fact, patients with chronic inflammatory diseases, who are at heightened risk of VTE, exhibit low vitamin B6 levels.¹⁶

From personal experience, I can testify that years of overuse of pyridoxine, especially by someone who is not eating regularly, can result in long-lasting sensory problems even if the doses taken are those normally prescribed or recommended on line. This is not an exclusive problem of the supplement industry, as most of the pyridoxine I have used has been a prescription medication.

Pyridoxine neuropathy is likely to be missed in diagnosis and could even be misdiagnosed as early MS (the difference is that pyridoxine toxicity affects the body symmetrically, MS is asymmetrical). The visual disturbance is interesting and unusual; objects are doubled in the horizontal plane, like watching a 3d movie without the glasses. I still notice this slightly when I look at spires or poles in the middle distance, although the other symptoms have completely cleared, albeit very slowly. Ketogenic dieting was helpful. At one time I could barely read.

Pyridoxine has a fascinating effect on dream recall (very tempting for an opiate addict). Take enough of it, and the very dream changes; a dream that allows you completely perfect recall can be a very vivid but barren dream, with bare floors, little furniture, simple and repetitive architecture, and little in the way of characters or events. The orthomolecular theory is that inability to remember one’s dreams is indicative of pyridoxine deficiency. It is certainly corrected by B6.
Maybe, like DVT, it is caused by a diet too dependent on processed meat and refined carbohydrate.