We recently had this letter on salt and hypertension published in the British journal, The Lancet. It’s unusual for the Lancet to publish favourable references to low carbohydrate diets. They tend to publish material supporting statins and fat-restricted dietary guidelines instead (thus setting up a series of controversies with the more reformist British Medical Journal. This probably helps the readership of both journals, and, by provoking open debate, generally advances the cause of science). So we’re very pleased that they thought the ideas in our letter sensible or informative enough to deserve publication.
Here we explain how we got drawn into this area, and why we think that the effects of LCHF on high blood pressure are relevant to people eating all kinds of diets.
Most people who start on a very low carbohydrate diet lose an extra pound or three or easily in the first week, and the conventional explanation is that this is nothing to get excited about as it’s water weight, water bound to glycogen that’s freed up when glycogen stores become depleted. We’ve never been happy with that explanation, because often the loss is much greater than the amount we’d expect from glycogen depletion.
In someone with hypertension, some of this water is actually part of the increased extracellular fluid volume that’s kept their blood pressure high. It’s good to be losing it.
In fact, if someone has high blood pressure, it’s very likely that they’ll be cutting down on medications quite soon after starting this diet – people with type 2 diabetes often reduce or come off blood pressure medication even before they cut down on blood sugar meds. We saw this in the very-low carb studies we reviewed for our New Zealand Medical Journal article on diabetes.
At the same time, you can start losing sodium easily, and you often need to supplement salt to keep your electrolytes in balance, when you cut carbs very low.
I’ve (GH) (and me (GS)) had this experience, getting cramps and feeling weak on a very low carbohydrate diet until I drank some water with extra salt, and I’ve also had the opposite experience of eating a salty high-carbohydrate meal in a Japanese restaurant and waking up visibly puffy from the retention of sodium and water. Such experiences are common.
The sodium (Na+) concentration in our body fluid needs to be kept within a quite narrow range, so if we’re retaining sodium we need to retain water and vice versa, and if losing, the opposite applies. And this system seems to be regulated by insulin – someone with type 1 diabetes who has no insulin will lose both electrolytes and fluid volume quickly.
So when we saw the study by Andrew Mente and colleagues in the Lancet, where most people tolerated high levels of salt long-term without increased systolic blood pressure or risk of CVD events or mortality, but in people with hypertension increases in blood pressure were associated with increasing sodium intakes, and increased CVD risk with high intakes, especially over 7 grams a day – which is a lot (in both groups low sodium intake, under 3 grams a day, was also associated with risk), we wondered whether the dietary context had an influence on this risk.
We looked to see what’s known about sodium reabsorption in the kidney, and found several experiments. The experiment we cited as our reference 5 has a particularly brilliant design – linking it to both the glucose and insulin concentrations in the blood. We also found that it’s well-accepted that essential hypertension is part of the metabolic syndrome, along with high insulin, elevated blood sugar, high triglycerides and low HDL.
(Essential hypertension is supposedly hypertension without known cause, it “just is”.
Actually, the distinction is to contrast it with hypertension secondary to some diagnosable physiological abnormality or disease – for example, portal hypertension, when cirrhosis of the liver inhibits the removal of blood by the liver from the portal vein, or hypertension due to kidney disease and so on.)
So it seems there may be a more coherent view of hypertension which explains why it appears in the context of metabolic syndrome.
We thought it is worthwhile for researchers to assess how much hypertension is associated with elevations in the insulin response to glucose. In other words, it’s worth looking for evidence as to whether this is (as we put it in our letter) due to to their not tolerating the amount of carbohydrate in their usual diet.
Because budgetary factors are important to the chances of any large study (the study in Mente et al was huge, n=133,118), we suggested the cheapest proxy for insulin, the fasting triglyceride/HDL ratio, which correlates quite well with the 2-hour insulin response to an OGTT in people without diabetes, and which are data that are in most people’s medical records already. The use of this proxy could be validated with the 2-hour insulin response to an OGTT in a subgroup if necessary. It can be seen in this study, chosen at random, that a doubling of the HDL/TG ratio (from ~2 to ~4 here) correlates with a doubling of the 2-hour insulin level (in table 2).
We already know that restricting carbohydrate in the diet is an effective tool for improving most cases of hypertension, but this sort of investigation would enable us to know with more certainty whether the consumption of modern high-carb diets lies somewhere on the causal pathway as well.
It’s not our position that dietary guidelines need to warn against high-carbohydrate diets – there’s no good evidence for that, they seem fine for plenty of people – but instead that they should supply clear information that restricted-carbohydrate diets are safe, and can be beneficial for weight management, blood sugar control, the management of blood pressure, and so on.
Researching this post brought up a very interesting animal study. In this experiment, a naturally hypertensive breed of rat was treated with high insulin doses. This greatly increased the animals’ blood pressure over baseline, and 4 of the 8 insulin treated rats suffered heart attacks – despite having no atherosclerosis, and not being fed cholesterol and high fat diets. Animals that are given atherosclerosis with high cholesterol diets don’t usually suffer heart attacks or other adverse effects. The placebo-treated hypertensive rats, and the insulin-treated normal rats, didn’t suffer heart attacks.
Demonstrating, perhaps, that high blood pressure plus high insulin is a dangerous combination, even when cholesterol is low. The discussion section of this paper is an interesting summary of the evidence for hyperinsulinaemia as causal in heart disease.
However, nothing in biology is ever quite as simple as we’d like it to be. Fuenmayor et al in 1998 found that insulin resistance in salt-sensitive, but not salt-resistant hypertension was worsened by high salt intakes. So these individuals may have an additional method to lower insulin, by avoiding high salt intakes. However high salt intake in this study was achieved by giving an extra 12 grams (3 teaspoons) of salt (4.6g sodium) a day on top of the low salt diet (this would take total intake to about 7g day), and this was not a cross-over study (7 days of low salt diet came first). Fasting and two-hour insulin in even the salt-resistant hypertensive cases was significantly higher than in non-hypertensive non-diabetics. The two-hour insulin is lower, as an artifact of the insulin suppression test used.
Fuenmayor et al concluded
Our observation is in line with the recent findings of increased insulin secretion in response to an oral glucose load in salt sensitive compared to salt resistant hypertensives. Therefore, carbohydrate administration (food intake) would induce silent hyperinsulinemia in salt sensitive patients. The elevated insulin levels may induce and worsen salt sensitivity and hypertension, and in the long term favor cardiovascular atherosclerotic complications.
Of course the quickest way to get too much salt and have your insulin raised too much by carbohydrate is to eat processed food. Avoid that, and it’s hard to overload on sodium just from occasional salty foods like feta, salted butter, and bacon. Use table salt (preferably iodised if you don’t eat a lot of seafood ) to taste. Have your blood pressure checked at the end of every doctor’s visit (seeing a doctor has been proven to raise your blood pressure, so only have it read once you’ve been seated for a while and have relaxed, if you can). If your blood pressure is too high, and you’re not eating heaps of salty or processed food, a LCHF diet may be a safer (and more effective) way to manage it than trying to cut salt as low as you can.
 Temelkova-Kurktschiev T, Henkel E , Schaper F, et al. Prevalence and atherosclerosis risk in different types of non-diabetic hyperglycemia. Is mild hyperglycemia an underestimated evil? Exp Clin Endocrinol Diabetes. 2000;108(2): 93-99.
 Zimlichman L, Zaidel S, Nofech-Mozes A et al. Hyperinsulinemia Induces Myocardial Infarctions and Arteriolar Medial Hypertrophy in Spontaneously Hypertensive Rats.
AJH 1997;10:646–653. zimlichman1997
 Fuenmayor N, Moreira E, Cubeddu LX. Salt sensitivity is associated with insulin resistance in essential hypertension. Am J Hypertens. 1998 Apr;11(4 Pt 1):397-402.
HDL cholesterol is one of the strongest predictors of both cardiovascular and cancer risk. It’s especially useful as this association seems to have no genetic basis, which implies it’s a modifiable risk factor. All non-drug interventions that improve health, for example by lowering weight, blood sugar, or inflammatory markers also raise HDL, including low carb diets, Mediterranean diets, and exercise. Raising HDL is usually considered a good thing. HDL is even called “good cholesterol” by the kind of ninnies who think that millennia of evolution have succeeded in producing something that deserves to be called “bad cholesterol”.
But there’s recent claims that high HDL is actually bad for cardiovascular disease at least,, after all.
CANHEART was a large (n= 631,762) pooled study in Canada, in which the association of HDL with mortality from CVD, cancer, and all other causes was determined over a follow-up period of 4.9 ± 0.4 years, during which there were 17,952 deaths.
Low HDL was associated with high death rates from all 3 causes, but surprisingly the CVD benefit plateaued at a fairly modest level, and very high HDL was associated with increased risk of non-CVD mortality. Especially levels over 90 mg/dl (2.33 mmol/l), but also over 70 mg.dl in men (1.81 mmol/l). CVD mortality overall was lowest in the range 51-90 mg/dl (1.32-2.23 mmol/l). These findings, as reported, supposedly debunk the idea that raising HDL is a good idea. Of course, raising HDL with drugs by sticking a spanner in the works at some point has never been an effective strategy and, as we shall see, there are genetic polymorphisms that give elevated HDL of little worth, but healthy diet and lifestyle changes that are reasonably expected to extend life always raise HDL a bit. Is this meaningless?
The levels associated with harm are very high HDL levels, and it’s relatively unusual to see levels this high in non-drinkers on LCHF diets, no matter how much coconut oil they eat. However, high alcohol intakes, as well as exposure to some drugs and toxins, can produce this effect, as can certain genetic variations. The conditions are collectively known as HALP, which is short for hyperalphalipoproteinaemia (we’ll stick with HALP).
One of the most common causes of HALP is alcoholism. Alcohol elevates HDL and at moderate intakes (around one standard drink a day) this is associated with benefit, but at high intakes there is no benefit and an increased risk of death from non-cardiovascular causes, including cancer. Ko at al in CANHEART claimed to have adjusted for excess alcohol intake, which was highest in those with highest HDL;
“Heavy alcohol consumption, as defined by the use of 5 or more drinks on 12 or more occasions per year was also included in the model for non-cardiovascular non-cancer death.”
I hate to break it to you, but getting drunk, even blind drunk, once a month will probably not raise your HDL much if at all. You really need to be a chronic alcoholic. In 2012, approximately 5 million Canadians (or 18 % of the population) aged 15 years and older met the criteria for alcohol abuse or dependence at some point in their lifetime, but how many at any one time qualify as chronically alcoholic is unknown. We know that Canadians have a per capita consumption of 10.2 litres of pure ethanol per year. That’s 27ml per day – a 200ml glass of wine – for every man, woman, and child over 15. If (for example) only 1 in 4 people drank regularly, that would be a bottle of wine a day each.
Even so, the data used in CANHEART to make the alcohol adjustment was far from complete.
“Since the use of smoking and alcohol was not available in entire CANHEART cohort, we imputed smoking status and heavy alcohol use for those with missing data based on the characteristics of the respondents to the Canadian Community Health Survey. Multiple imputation using complete observations and 10 imputation datasets was conducted. Smoking status was available for 5,093 individuals and alcohol use was available for 5,077 individuals who completed the survey.”
This was a tiny fraction of the 631,762 individuals in the study – less than 1% – and it involved voluntarily self-reported health data;
The Canadian Community Health Survey (CCHS), an ongoing Canada-wide population-based survey that collected information on self-reported health status, health determinants, and health care utilization
Alcohol intake is known to be misreported in dietary surveys by a factor of 2-3. Alcoholism is probably under-reported to health professionals to a much greater extent, especially in countries where health insurance is a major factor in access to care.
Another confounder is the effect of genetic polymorphisms. One genetic cause of very high HDL is a CETP defect.
“…the in vitro evidence showed large CE-rich HDL particles in CETP deficiency are defective in cholesterol efflux. Similarly, scavenger receptor BI (SR-BI) knockout mice show a marked increase in HDL-cholesterol but accelerated atherosclerosis in atherosclerosis-susceptible mice. Recent epidemiological studies in Japanese-Americans and in Omagari area where HALP subjects with the intron 14 splicing defect of CETP gene are markedly frequent, have demonstrated an increased incidence of coronary atherosclerosis in CETP-deficient patients. Thus, CETP deficiency is a state of impaired reverse cholesterol transport which may possibly lead to the development of atherosclerosis.”
The CANHEART authors, Ko et al, do not mention the likelihood of such conditions affecting their analysis. Even if we assume that both chronic alcoholism and genetic HALP are rare conditions, men with HDL over 90mg/l were less than 0.3% of the study population, and of these few men, only a few dozen died during the study. The exact number isn’t clear because the only mortality data given is for adjusted age-standardized rates per 1,000, but from total deaths and these rates we estimate it to be (at the very most) 70-80 deaths, of which 30-35 were non-cardiovascular and non-cancer deaths, out of about 2240 men. The majority of alcohol-related such deaths in Canada are due to alcoholic liver disease, motor vehicle accidents and alcohol-related suicides. Had Ko et al given a breakdown of non-cardiovascular causes of death for the highest HDL categories, it would have been relatively easy to tell how many of these were due to alcoholism.
Overall, people in the high HDL categories at baseline exercised more, had lower triglycerides, less diabetes, lower LDL, more ideal BMI, and ate more fruit and vege than people in the middle and lower ranges.
Did these things cause them to die at a higher rate?
Here’s an alternative explanation – the baseline characteristics represent only the vast majority of people in each category. The vast majority of people in each HDL category, even the highest, didn’t die. Even people with genetic HALP can be healthy. The people who died in the high HDL categories tended to be the people with alcoholism, drug induced HALP, and poorly-managed genetic HALP, and their baseline characteristics, had they been isolated, would have been quite different. These are the people for whom high HDL is not protective, and, as their numbers increased in categories of increasing HDL, the usual dose-response relationship between HDL and cardiovascular disease and cancer, seen in better-controlled populations, was lost.
(There would also have been metabolically healthy individuals who had low HDL for genetic reasons doing well in the low HDL category. For this reason the TG/HDL ratio and other available risk factors still need to be taken into consideration when evaluating HDL).
Healthy HALP seems to require low insulin and low triglycerides (TGs). This is exactly what we see in insulin-sensitive individuals, and in people whose HDL rises on the LCHF diet.
In hyperalphalipoproteinemia cases, we found a diminished TG/HDL-C plasma ratio that has been deemed as critically dependent on insulin activity. Although the plasma CETP activity measured by the exogenous method that reflects the plasma CETP concentration did not differ between the two groups the low TG/HDL-C likely is consequent to decreased endogenous CETP activity due to a diminished triglyceride availability from apoB-containing LP for exchange with HDL cholesteryl ester in hyperalphalipoprotaeinemia cases. In agreement with a primary role for insulin sensitivity in cholesterol metabolism and, to a considerable extent, in plasma HDL-C concentration variation, we found a diminished ALT level within the “reference” range in hyperalphalipoprotaeinemia cases, a result compatible with other reports relating ALT to insulin sensitivity.
A possible criticism is the way that Ko et al have interpreted the-lipid lowering trial data to support their thesis. This is only valid if their intention is to discourage the use of HDL as a drug target. (Incredibly, pharmaceutical companies have invested billions in developing drugs that inhibit CETP, and have continued to test these despite sometimes disastrous and always disappointing results, the latest trial ending as recently as 2016).
They say “Several contemporary studies have shown a lack of significant association of HDL-C levels and outcomes for patients on higher-intensity statins, with coronary artery disease, or who had undergone coronary artery bypass graft surgery (12,13,15).”
However, reference 12 states
“In 8901 (50%) patients given placebo (who had a median on-treatment LDL-cholesterol concentration of 2.80 mmol/L [IQR 2.43-3.24]), HDL-cholesterol concentrations were inversely related to vascular risk both at baseline (top quartile vs bottom quartile hazard ratio [HR] 0.54, 95% CI 0.35-0.83, p=0.0039) and on-treatment (0.55, 0.35-0.87, p=0.0047). By contrast, among the 8900 (50%) patients given rosuvastatin 20 mg (who had a median on-treatment LDL-cholesterol concentration of 1.42 mmol/L [IQR 1.14-1.86]), no significant relationships were noted between quartiles of HDL-cholesterol concentration and vascular risk either at baseline (1.12, 0.62-2.03, p=0.82) or on-treatment (1.03, 0.57-1.87, p=0.97). Our analyses for apolipoprotein A1 showed an equivalent strong relation to frequency of primary outcomes in the placebo group but little association in the rosuvastatin group.”
In other words, people in the top quartile for HDL and ApoA1 on placebo had the lowest vascular risk, and these people got little if any extra benefit from LDL lowering with a statin. And because we are looking at quartiles, not isolating a small number of people who have freakishly high HDL for some reason, there is a true dose-response effect of HDL between quartiles in the placebo arm.
This effect has been seen in multiple trials. Drug trials are likely to exclude alcoholics and binge drinkers.
The evidence tells us that the predictive value of HDL is excellent, but is lost when people are undergoing intensive treatment for coronary artery disease, a classic case of Goodhart’s law, “When a measure becomes a target, it ceases to be a good measure.” We see this again and again with intensive drug treatment to manipulate metabolic markers.
Thankfully, it doesn’t seem to apply to diet and lifestyle interventions.
What is HDL?
High-density lipoprotein or HDL is, like LDL, a large particle made up of various lipids and proteins (notably Apo A1 in the case of HDL, Apo B in the case of LDL) which is produced by the liver. Its role in cholesterol metabolism is to collect unwanted cholesterol, which is converted to cholesteryl esters (CE) by the addition of a fatty acid and transferred to LDL particles by CETP (cholesteryl ester transfer protein) for conveyance back to the liver. If CETP is deficient or inhibited CE accumulates in HDL, and LDL cannot complete its removal. Excess triglycerides (TG) from VLDL can also be transferred to HDL, and when the HDL particles become overloaded with TG they are unable to function as CE carriers and are removed from circulation, thus the association of high TG with low HDL and increased CVD risk.
 Ko DT, Alter DA, Guo H, et al. High-Density Lipoprotein Cholesterol and Cause-Specific Mortality in Individuals Without Previous Cardiovascular Conditions: The CANHEART Study. J Am Coll Cardiol. 2016;68(19):2073-2083. doi:10.1016/j.jacc.2016.08.038.
 Yamashita S, Maruyama T, Hirano K, Sakai N, Nakajima N, Matsuzawa Y.
Molecular mechanisms, lipoprotein abnormalities and atherogenicity of hyperalphalipoproteinemia.
Atherosclerosis. 2000 Oct;152(2):271-85.
 Leança CC, Nunes VS, Panzoldo NB et al. Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects. Cardiovascular Diabetology 2013, 12:173.
 Ridker P.M., Genest J., Boekholdt S.M., et al; for the JUPITER Trial Study Group. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial. Lancet. 2010;376:333-339.
By George Henderson and Grant Schofield
Ancel Keys has become a kind of cartoon villain for dietary reformers for various reasons – allowing ecological epidemiological comparisons to dominate his thinking, attacking John Yudkin’s sugar hypothesis with made-up ecological claims, and basically (with a lot of help) bullying his rivals out of their labs and grants so that their science couldn’t undermine his and that of his mates.
Is there redemption? Did we get something wrong? Is he a good guy after all?
Ancel Keys had a first-class mind, and this was the main reason he won his battles. His work should not be ignored, any more than we should ignore the work of George Bernard Shaw or H.G. Wells because their ideas of social improvement led them eventually to support eugenics and dictators like Stalin. In this paper on the Roseto effect, Keys performs a valuable function – he debunks an early example of what would today be called ‘psychobollocks’. keys-roseto-2
The Italian immigrants of Roseto ate a diet high in red meat and animal fat (lard), and also high in starchy carbohydrate, the source of which no-one seems to have recorded. They avoided olive oil and had a seemingly low rate of heart attacks, supposedly due to relatively stress-free lives (the evidence for which was questionable). Keys shows that most of this supposed reduction in heart attacks is due to variation in coding the causes of death. And what is left over, he attributes to the Italians’ diets before immigration, and the fact that Italian immigrant diets had more monounsaturated fat and less saturated fat than the usual American diets. We also note (which Keys didn’t) that the inhabitants of Roseto drank wine instead of the soft drinks drunk by other Americans.
In this paper, Keys lays out the diet-heart hypothesis as it existed in 1965 –
But it is desirable to clarify the dietary problem.
STOUT et al.  discredit the hypothesis that dietary fat is important in atherogenesis
and its clinical complication in the form of coronary heart disease. Actually, the hypothesis that most proponents offer is not as simple as they indicate. One statement of the hypothesis is: “Atherogenesis in the coronary arteries is promoted by increasing concentration of cholesterol in the ß-lipoprotein in the blood plasma and this cholesterol concentration is raised by increasing the proportion of dietary calories supplied by saturated fatty acid, the poly-unsaturated fatty acids having a weaker opposing influence”.
A more modern and updated version of this, based on evidence from 60 controlled diet trials:  Just remember that Apo B is in LDL and similar particles, and tends to correlate with the small dense, and potentially harmful LDL sub-fraction. Keys knew about these, and they are resurfacing again today as an important marker of arterial health. Apo A1 is in the HDL sub-fraction which is associated with benefit.
Replacement of carbohydrates with SFAs did not change apo B concentrations. The cis unsaturated fatty acids, however, decreased apo B, and this effect was slightly stronger for PUFAs. SFAs and MUFAs increased apo A-I concentrations relative to carbohydrates. PUFAs did not significantly change apo A-I concentrations.
Apo B correlates to non-HDL cholesterol in people eating the normal diet, and less precisely to LDL cholesterol, whereas Apo A1 correlates with HDL cholesterol.
How did we get from this to a low fat diet?
Below we show you how. The low fat diet has potential to provide some benefit in improving particles. But the low carb diet is much better.
If we compare the 10% SFA, 30% fat dietary guidelines diet with a typical LCHF diet with unrestricted saturated fat, and fat from a variety of sources, we can see that the LCHF diet actually has the potential to lower Apo B much more than the low fat diet, despite having twice as much saturated fat. It also has more potential to increase Apo A1. The absolute levels of Apo B and Apo A1, and the ratios between them, are actually better predictors of heart disease risk than are LDL, HDL and their ratios.
The dietary guidelines diet:
Ignoring protein, only 20 % of this diet will lower Apo B, only 25% will increase Apo A1
50% UFA (5% PUFA)
50% of this diet will lower Apo B, 65% will raise Apo A1.
For some reason, when Ancel Keys came to test his hypothesis in 1968 in Minnesota, people were so opposed to increasing fat in the diet that he could only try to lower Apo B by replacing about 9% of the SFA in the diet with an equal amount of linoleic acid from corn oil (an intervention which wouldn’t have increased MUFA). This gave him a very small leverage in terms of Apo B compared to our example, offset by a negative effect on Apo A1.
He did this despite being on record as sceptical about the value of high linoleic acid (PUFA) intakes. Why? Maybe he had painted himself into a corner with his original ecological studies correlating fat with heart disease mortality. Maybe he had to compromise with the Harvard crew, Hegsted and Stare, who had already sold out to sugar interests. Even for someone as influential as Keys, setting up a big study was a co-operative effort that required the support of most of the major players in the field. In any case, the Minnesota study didn’t show that replacing SFA with linoleic acid reduced CHD mortality.
So, are there studies that support our hypothesis, that LCHF reduces CHD risk without SFA restriction? Just as in Keys day, few people can get funding for a long-term, large study that increases fat in the diet. The PREDIMED study is probably the only example; in this case, the diet arms with an increase in MUFA from olive oil (an extra 50g per day), or an increase in total unsaturated fats from nuts and olive oil (6 servings per week and 32g per day respectively), experienced lower risk of major CVD events compared to controls. (Those in the control group received small nonfood gifts, which was nice.) This is not a test of a high-SFA diet, as the subjects were complying with a supposed Mediterranean diet (i.e. not any real one but the version created recently by academics), but it does test the effect of increases in MUFA.
The median follow-up period was 4.8 years. A total of 288 primary-outcome events occurred: 96 in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). Taking into account the small differences in the accrual of person-years among the three groups, the respective rates of the primary end point (major CVD events) were 8.1, 8.0, and 11.2 per 1000 person-years. The unadjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.70 (95% CI, 0.53 to 0.94) for a Mediterranean diet with nuts as compared with the control diet (P=0.015, by the likelihood ratio test, for the overall effect of the intervention). HRs for all but stroke were non-significant after multivariant adjustment.
There are a few recent epidemiological studies showing reduced CVD risk in higher-fat populations, with little or no adverse effect of SFA, including the high-quality Malmö Diet and Cancer Study. (n=28,098; 1250 deaths).
For men, a significant trend towards lower cardiovascular mortality in upper quartiles of total fat intake was observed (P = 0.028) with the RR for men in the fourth quartile being 0.65 (CI 0.45–0.94, P = 0.023) (Fig. 1). No difference was observed between quartiles of saturated fat intake for men. Having relatively high intakes of monounsaturated or polyunsaturated fats compared with saturated fats did not show benefit for either sex.
Although this association only exists for men in Malmö, this is important for 2 reasons – men have a much higher cardiovascular disease risk compared to women (3-4x in Sweden during these years), and cholesterol and LDL-cholesterol – the imprecise Apo B proxys – correlate with CVD risk in men in this age group, much more so than in women. Mean fat consumption by men in the upper quartile was 47.7% of energy – a respectable amount.
Similar findings came from the recent Harvard paper on fat and mortality in the combined Nurses’ Health Study and Health Professionals’ Follow-up Study (we wrote about this a while back).
After adjustment for known and suspected risk factors, dietary total fat compared with total carbohydrates was inversely associated with total mortality (hazard ratio [HR] comparing extreme quintiles, 0.84; 95% CI, 0.81-0.88; P < .001 for trend).
And, in memory of Keys, here’s a recent ecological (between-country) study: 
We found exceptionally strong relationships between some of the examined factors, the highest being a correlation between raised cholesterol in men and the combined consumption of animal fat and animal protein (r=0.92, p<0.001). The most significant dietary correlate of low CVD risk was high total fat and animal protein consumption. Additional statistical analyses further highlighted citrus fruits, high-fat dairy (cheese) and tree nuts. Among other non-dietary factors, health expenditure showed by far the highest correlation coefficients. The major correlate of high CVD risk was the proportion of energy from carbohydrates and alcohol, or from potato and cereal carbohydrates. Similar patterns were observed between food consumption and CVD statistics from the period 1980–2000, which shows that these relationships are stable over time. However, we found striking discrepancies in men’s CVD statistics from 1980 and 1990, which can probably explain the origin of the ‘saturated fat hypothesis’ that influenced public health policies in the following decades.
If the older epidemiological studies available to the original diet-heart enthusiasts didn’t show the same protective effects of total fat intake, this is perhaps because there was more trans fat in the food supply a few decades ago, or perhaps because modern studies are better controlled for carbohydrate quality and other factors.
The higher intakes in these studies of usual diets are usually around 40-50% fat, so they’re not actually low carb diets, but they are getting close, whereas our hypothetical LCHF example was 70% fat (which still allowed a generous hypothetical 75g of carbohydrate per day).
However – if Key’s hypothesis, and the prevailing appearance in his day of fat and SFA as associated with CVD mortality in epidemiology, was able to launch dozens of long-term studies of fat and saturated fat reduction for prevention of CVD, why is it that today, with a more up-to-date version of that hypothesis and at least as much epidemiological and experimental support for it, there are no trials, and instead we’re getting reheated leftovers of the old trials and their feeble and uncertain results, in the form of endless meta-analyses of the same data sets?
If you’ve read this far, you may appreciate this French documentary about the diet-heart hypothesis, which has some cool old footage of Ancel Keys and his crew.
There’s a particularly shocking bit in the middle where Jerry Stamler goes mad and starts telling us to throw away egg yolks. This marks the exact point at which the diet-heart hypothesis became an official licence to produce thousands of profitable low fat processed foods, with no regard for their actual nutritional value
* Nina Teicholz has pointed out that the only source of saturated fat associated with increased risk in this PREDIMED paper was “pastries and processed foods”. Meat, processed meats and dairy were safe sources of SFA.
 Keys A. Arteriosclerotic heart disease in a favored community. J chron Dis. 1966, Vol. 19, pp. 245-254.
 Mensink RP, Zock PL, Kester ADM, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr May 2003
vol. 77 no. 5 1146-1155. http://ajcn.nutrition.org/content/77/5/1146.full
 de Nijs T, Sniderman A, de Graaf J. ApoB versus non-HDL-cholesterol: diagnosis and cardiovascular risk management. Crit Rev Clin Lab Sci. 2013 Nov;50(6):163-71.
 Walldius G, Jungner I. The apo B/apo A-I ratio – a new predictor of fatal stroke, myocardial infarction and other ischaemic diseases – stronger than LDL and lipid ratios. Atherosclerosis. 2006;7(suppl):468. Abstract Th-W50.6.
 Ramsden CE, Zamora D, Majchrzak-Hong S et al. Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ 2016; 353
 Estruch R, Ros E, Salas-Salvadó J et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N Engl J Med 2013; 368:1279-1290.
 Wang DD, Li Y, Chiuve SE et al. Specific Dietary Fats in Relation to Total and Cause-Specific Mortality.JAMA Intern Med. 2016 Aug 1;176(8):1134-45.
 Guasch-Ferré M, Babio N, Martínez-González MA, Corella D et al. Dietary fat intake and risk of cardiovascular disease and all-cause mortality in a population at high risk of cardiovascular disease. Am J Clin Nutr. 2015 Dec;102(6):1563-73. doi: 10.3945/ajcn.115.116046.
 Grasgruber P, Sebera M, Hrazdira E et al. Food consumption and the actual statistics of cardiovascular diseases: an epidemiological comparison of 42 European countries. Food & Nutrition Research [S.l.], v. 60, sep. 2016. http://www.foodandnutritionresearch.net/index.php/fnr/article/view/31694
A nice quote from reference :
The efficacy of replacing SFAs with carbohydrates depends on the effects on body weight in the long term, and that effect is uncertain.
Drs David Katz and Garth Davis are a good example of the type of crypto-vegan medical professional who believe in the power of the “plant based diet”. They have a knee jerk reaction to low carb diets, because they think these involve eating more meat.
Here’s a news flash – you can eat more meat on a low carb diet (because who knows if you ate any before), but you don’t need to, and you may well eat less, just because you’ll probably be eating less anyway, without much effort. …And LCHF well formulated is a high plant diet.
Newsflash 2: Cereals aren’t plants. They are highly processed foods made in factories.
Newsflash 3: You can eat a plant-based diet and be LCHF if you want.
But there’s more to it than just these revelations. There is a deeper unscientific criticism of LCHF, from scientists, which needs to be uncovered. Here it is.
They presented a blog on the Very Well website, a health and lifestyle platform which has also run more positive articles about LCHF, that’s critical of Drs Sarah Hallberg and Osama Hamdy’s recent opinion piece in the New York times saying that LCHF diets can be a viable alternative to bariatric surgery for diabetes.
Katz is from Yale (see his www site), and in our view is a “fence sitter” who criticises LCHF and other approaches which should be given as an option.
Katz introduces Davis, who then makes some numbered points. In our opinion these are all off the mark, and the condemnations of LCHF in particular include pseudoscientific scare stories; the sort of things that plant-based diet advocates fear will happen to them if they stop eating wholegrain cereals, but for which there is absolutely no evidence at all.
1. The authors imply that weight loss surgery is not effective.
Nowhere in the NYT article was it implied that bariatric surgery is ineffective.
In fact, though any surgery carries both a risk and a hefty price tag, there is good evidence that some forms of bariatric surgery are effective at reducing weight and reversing diabetes. Garth Davis, who is a bariatric surgeon, says “I see 80 percent to 85 percent of my gastric bypass patients off their diabetic medications five years later”, and this is a good result. Unless you are one of the other 15-20% (which is it?), some of whom may well have undergone a much bigger commitment than dieting for no improvement.
Dr Davis says “Long-term side effects of low-carb dieting may include high cholesterol, cardiovascular disease, kidney stones, bone loss, erectile dysfunction, malnutrition, and an increased risk of cancer.”
We have never heard of most of these; cholesterol usually goes down (if it’s high), it can sometimes go up, but there’s no evidence that rises in cholesterol related to carbohydrate restriction increase cardiovascular disease, and reason to think that they are at worst neutral. Why you would experience bone loss on any well-formulated diet, we can’t begin to think, but again there’s no record of this happening. A 24-month study of the Atkins diet found no new cases of kidney stones, and no change in bone density (in any case, these concerns belong to very high protein diets). As with erectile dysfunction; there’s no data on this either, but all these U.S. plant-based dudes seem to be very defensive about virility, maybe because of the scare stories about soy isoflavones. Malnutrition? That’s up to your dietitian, surely, but if you eat real food and mix up a good variety of animals and vegetables you can’t go wrong.
Cancer, of course, is the big scare story. We all know we’ll get cancer if we eat red meat or forget to eat our wholegrain fibres. Unfortunately there’s no good evidence for this. Diabetes (defined by high blood sugar) increases the risk of every cancer except prostate cancer, and a higher HDL level is associated with reduced risk, showing an obvious point at which diet influences risk. Ketogenic diets have actually shown promise for reducing cancer growth in early research.
As for meat, there is an interesting finding from the EPIC-Oxford study. It was a study of “health conscious” individuals (i.e. with less confounding from unhealthy behaviours), and in this population, which had a low mortality rate overall, vegetarians had a significantly higher rate of colorectal cancer than meat eaters.
“The incidence rate ratio for colorectal cancer in vegetarians compared with meat eaters was 1.39 (95% CI: 1.01, 1.91).“ 
Garth Davis fails to list the long-term side effects of bariatric surgery. Unlike the long-term low-carb diet side effects listed, these are not imaginary or conjectural but a matter of medical record. For example (these are just some listed)
Nutritional deficiencies are a common after-effect of surgery.
Between 13% and 36% of patients develop cholesterol gallstones after surgery, due to rapid weight loss, but only 10% develop symptoms requiring surgical intervention. (cholesterol gallstones are a common side-effect of rapid weight loss on low-fat diets, but not LCHF diets).
8% to 10% of patients developed incisional hernias after open bariatric surgery.
Less than 5% to 10% of patients have chronic problems with dumping syndrome, which can cause facial flushing, lightheadedness and diarrhoea after eating carbohydrate-rich meals. Most patients find that reducing their intake of carbohydrates and avoiding drinking liquids half an hour before and after eating improves their symptoms.
So some common side effects of bariatric surgery can be lessened or avoided by restricting carbs after surgery. Maybe this also helps to explain why 80-85% of Dr Davis’s patients can remain free of diabetes medications. These side effects are more common than the supposed serious side effects of LCHF, which have not been reported in RCTs, so we can’t even put a % figure on them.
2. They assume that patients who see bariatric surgeons have never tried dieting endlessly and over all types of diet before.
In fact, all of our practice’s patients have tried weight loss diets, multiple times. Many have dieted since “fat camps” as children. The number one diet our patients attempt is the Atkins diet (a popular low-carb approach), often numerous times, resulting in a fear of carbohydrates.
Nobody goes into surgery without having given a valiant effort at dieting. For many insurance companies, preoperative attempts at dieting are mandatory, and I know very few surgeons who would operate on a patient that has never tried to lose weight before.
If you go to a bariatric surgeon to reverse diabetes, clearly you have a serious medical problem. You want to be dieting in a way that’s supported and encouraged by your health providers. This is unlikely at present to be the Atkins diet (which can mean a number of different low carb approaches, including diets high in processed foods, or high in protein). Garth Davis plainly doesn’t support the LCHF approach, so his testimony about it can only be second-hand and anecdotal. Why might the “Atkins” diet fail these patients? There’s a clue in the recent Fat vs Carbs documentary on Welsh BBC TV. Presenter Jamie Owen goes on the LCHF diet to lose weight (it works, and his cholesterol goes down). Before he starts, his GP and the dietitian consulted say that he should follow it for “no longer than 3 weeks”. Really?
If you’re not supported in your efforts long-term, if you have “experts” sniping from the sidelines about cancer risk this and bone loss that, it takes a stubborn person to get good long-term results. Dr Sarah Hallberg, on the other hand, supports her type 2 diabetes patients to follow the LCHF diet, as does Dr David Unwin in the UK, and their patients don’t have a high failure rate at all. Plainly, if you do LCHF differently, you can get different results.
The bariatric surgeon is the ambulance at the bottom of the cliff. All other objections aside, it would be impossible to treat every case of diabetes by this method, no matter how effective.
3. The authors reveal a lack of knowledge as to the root mechanism that causes diabetes.
They seem to assume that diabetes is simply a result of high blood sugar, when in fact the high sugar is the symptom, not the cause, of diabetes. Lower carbohydrate intake will drop blood sugar, but it does not address the central issue—the body is no longer able to process the carbs.
In reality, diabetes is caused by uptake of fat into muscle and liver cells. This greatly impedes the body’s ability to make insulin receptors, and without insulin receptors, sugar cannot get into the cell. The low-carb diet will lower blood sugar, but it will not fix the underlying problem of insulin resistance.
Here, it is Davis and Katz who shows poor understanding of mechanisms. High carbohydrate intakes in people with type 2 diabetes push insulin high, and insulin is what governs the accumulation of fat in the body, including in muscle and liver (and pancreas) resulting in insulin resistance (insulin itself downregulates the insulin receptor if present in excess). On a very low carbohydrate diet, insulin drops and this fat is released and oxidised, restoring insulin sensitivity. Very low carb diets are highly effective for reducing liver fat (a bariatric surgeon should know this).
Sugar can get into cells without insulin receptors – glucose uptake is not the main problem in diabetes – instead, insulin resistance means that the liver doesn’t stop releasing glucose when you eat carbs. It’s the failure of insulin’s inhibitory effect that defines diabetes and results in high blood glucose.
The effects of this ‘black age’ are still with us because these incorrect hypotheses have, with the passage of time, been turned into dogma and become cast into ‘tablets of stone’ in undergraduate textbooks. They are also carried forward into postgraduate teaching. For example, even in well respected texts it is still common to find statements such as ‘The basic action of insulin is to facilitate glucose entry into cells, primarily skeletal muscle and hepatocytes.’ – Sonksen and Sonksen 
4. They suggest that the low-carb diet was the favored and only diet for diabetes until recently.
This is just false. In fact, at Duke University in the 1940s, Walter Kempner, MD, treated diabetes successfully with the Rice Diet.
Randomized clinical trials beginning in 1976 collectively highlight the efficacy of a plant-based diet in diabetes management. And recent studies funded by the National Institutes of Health (NIH) have shown us that plant-based diets are even more effective than the traditional American Diabetes Association (ADA) diet plan. As a result, the ADA includes plant-based eating patterns as a meal-planning option in their nutrition recommendations for people with diabetes.
In fact, Davis is distorting history here. The rice diet was never mainstream, and in any case was a highly restrictive inpatient diet, whereas pre-insulin LCHF diets like the Michigan Diet were designed to support patients with enough energy to stay active and keep working.
It doesn’t surprise us that plant-based diets are more effective than the ADA diet plan. As far as we know, every therapeutic diet that has ever been tested has been shown to be more effective than the ADA diet plan. Replacing refined carbs and denatured fats with their equivalents in real foods, even in plant form, is obviously going to slow the appearance of glucose in the blood and lower elevated insulin. That’s why the LCHF diet includes lots of non-starchy vegetables, low-sugar fruits, and fatty fruits and nuts. It’s often a plant-based diet too, if by that is meant a diet high in unprocessed plant food by volume.
Fifth: The authors insinuate that low-carb diets have somehow been erroneously abandoned and should be brought back.
The idea is that low-carb diets worked but the “low fat craze” prematurely, and inappropriately, ended the popularity of the low-carb diet. Low-carb diets have been around since the 1800s. There have been numerous best-selling books through the years touting low-carb dieting as the holy grail. Yet, the diet has repeatedly fallen out of favor, not because of some low fat conspiracy, but because side effects have kept it from being utilized long term.
One might ask, where is the rice diet now? Does anyone at all still use it?
In any case, this is not the reason the low-carb diet fell from favour. Its use declined in diabetes treatment because the mass-production of insulin made it seem unnecessary; its use for weight control declined after the 1960s for the reasons Dr David Ludwig gives in his recent JAMA article, and this – with very little testing, and no testing at all of the very low-carb diet – further.influenced diabetes recommendations.[7,8] After which time obesity and diabetes really did take off – if dietary treatment of these conditions had actually improved in the low-fat, low-animal fat era, this would probably not have happened.
Dr Sarah Hallberg and others are using the LCHF diet on an increasingly large scale and making it work for their patients. Instead of attacking them (and the real reason for this here seems to be opposition to the inclusion of animal foods and animal fats in the diet), why not study what they’re doing right? Hint: it involves including enough real foods – fatty animal foods and low carb vegetable foods – that people don’t feel deprived and persist in the diet long enough to adapt to it. It becomes a way of life – or, at least, a way of eating – that promotes health and enjoyment, and not a crash diet or another fad.
Telling a morbidly obese patient with diabetes to go on yet another low-carb diet is a form of fat shaming and is completely inappropriate management of this disease.
My suggestion to patients dealing with obesity and diabetes is to eat a predominantly whole foods, plant-based diet and to exercise.
Huh? Come again? The other guy’s diet advice is automatically fat-shaming, but your advice to eat virtuously and exercise (I bet they’ve never heard that before) isn’t?
 Friedman AN, Ogden LG, Foster GD et al. Comparative Effects of Low-Carbohydrate High-Protein Versus Low-Fat Diets on the Kidney. Clin J Am Soc Nephrol. 2012 Jul; 7(7): 1103–1111. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386674/
 Key TJ, Appleby PN, Spencer EA et al. Cancer incidence in vegetarians: results from the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford). Am J Clin Nutr. 2009 May;89(5):1620S-1626S. doi: 10.3945/ajcn.2009.26736M. [link]
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 Henderson G. Court of Last Appeal – The Early History of the High-fat Diet for Diabetes. J Diabetes Metab. 2016; 7:696. doi: 10.4172/2155-6156.100696
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 Schofield GM, Henderson G, Thornley S. Very low-carbohydrate diets in the management of diabetes revisited. N Z Med J. 2016 Apr 1;129(1432):67-74.
Once again, the significance of a mouse study has been distorted by its authors and exaggerated by the media. It grabbed our attention because it was the lead front page story in our national newspaper the New Zealand Herald, no less. Also, because we’ve been big advocates for lower carb intakes, especially for the insulin resistant amongst us, it flies in the face on what we are on about.
So let’s have a look at what’s going on.
Common dietary advice has been turned on its head by new research finding that a low protein, high carbohydrate diet stimulates a hormone dubbed the “fountain of youth”.
The Sydney University group led by Dr Samantha Solon-Biet says a high-protein diet is good for reproductive health in younger adults, but recommends switching to a low-protein diet rich in vegetables and other natural carbohydrates from age 50 or 60 to live longer.
“A diet that optimises later-life health has a protein-to-carbohydrate ratio of 1:10,” Solon-Biet said.
The hormone this mouse study looks at is a protein called FGF-21. There is absolutely no evidence that this is a “fountain of youth” and really the myth of Ponce de León should be a warning to all these researchers – he never found the Fountain of Youth because it didn’t exist. Where this mouse research is interesting is because FGF-21, as well as having potentially useful effects in terms of insulin sensitivity, seems to be specifically important with regard to our appetite for sweet carbohydrates – when FGF-21 levels are high, carb cravings stop. So FGF-21 goes up when we eat carbs, so we know when to stop – but there’s such a thing as FGF-21 resistance, if levels are too high for too long we can become insensitive to it. FGF-21 levels also go up in other situations where we don’t need carbs – in prolonged fasting, or on a ketogenic diet. When you lose your sweet tooth after a few weeks on LCHF, that’s probably (in part) due to either a decrease in FGF-21 resistance or a rise in its level.
“FGF21 is increased in various conditions such as overfeeding, obesity, insulin resistance, starvation, protein/amino acid deprivation, low-protein ketogenic diets, and high carbohydrate feeding, yet the metabolic effects are very different in each nutritional context.”
But it’s very important to realise that thousands of proteins are involved in complex processes like the regulation of appetite. Maybe FGF-21 is to carbohydrate what leptin is to fat, but it’s very much early days still.
Auckland University Professor Wayne Cutfield said the Sydney study was based on mice, not humans, and looked at only one hormone called FGF21 out of a large number of hormones and other factors which interacted with each other.
“FGF21 is one of many factors involved in regulating our lifespan. To say that FGF21 is ‘the one’ is just not true,” he said.
Herald health and fitness commentator Lee-Anne Wann said people should not rush out and eat more carbohydrates to increase their FGF21.
“It’s great that they are looking at it. We’ve looked at other things like leptin which help manage our appetite, we are always finding new things,” she said. “But it’s too soon to be saying, ‘Oh my god, we should be increasing carbohydrates.”
In this instance the Herald reporter Simon Collins has done a good job (if we accept that these claims needed to be covered at all; but it will be big news in Australia for political reasons). The NZ experts he interviewed really don’t buy into the hype.
How was the study designed? In a somewhat confusing way. Mice were fed 25 different diets, and the paper isn’t clear what these were, except that they had various permutations of the 3 macronutrients. However, if they were the usual mouse diets, the carbohydrate would be mostly maltodextrin, the protein casein (just one of the proteins in milk, but the one which has a bit of a dodgy reputation when considered on its own). The fat could be anything – lard, cocoa butter, canola. Fortunately not much is being made of fat here.
But there’s a red flag – the mouse diet was not “rich in vegetables and other natural carbohydrates”. In fact, the odds are very high that it actually supplied none.
How were the results presented? Again in a somewhat confusing way. These scientists like using a novel kind of data visualisation, but fortunately they did provide this clearer summary.
Here’s your Fountain of Youth.
Eating a protein restricted, high carbohydrate diet maximises FGF21, but this results in an increased appetite for protein, for which FGF21 may be responsible.
If FGF21 was the Fountain of Youth, then, to exploit this, you would need to eat in such a way that you would always be craving protein, and then, if you did eat enough protein, you’d lose your FGF21 advantage.
This does not sound like much fun, even for a mouse. Protein foods are flavoursome, come in considerable variety, and are excellent sources of vitamins, minerals, essential fats, and energy. The LCHF diet isn’t, and the Paleo diet needn’t be, high protein at all, but for humans there is a real advantage to keeping muscle on our bodies (mice, for example, don’t need to open jars or lift the furniture often). This helps us to stay active, makes us more useful in our daily lives, and helps with physical and mental health. Losing muscle because of some fad diet idea (sic) that involves restricting protein for longevity (rather than for some measurable shorter term benefit, which you can actually check) is perhaps not the first thing that scientists should promote in the media. Surely every mouse experiment doesn’t have to generate a headline – there are enough human experiments to be going on with.
But I guess “high carbs key to long life” in a headline is just irresistible.
The discussion part of the paper is indeed interesting, and at least some of these 20 researchers really do know their stuff, but some of them seem to be extrapolating from it in the media as evidence that one type of traditional human diet out of thousands is healthier than all the others. The facts are, that
- all traditional, pre-industrial diets are more-or-less healthy except when resources are poor.
- populations eating diets high in meat and cheese (Sardinia) can be as long-lived as populations eating yams with low protein (Okinawa), and there are also shorter-lived populations eating both types of diet.
- if we are no longer eating these traditional diets, we are more likely to have have metabolic disease or other health conditions that are rare in traditional populations, and which usually respond to specific and perhaps novel dietary changes – even peasants emigrating from the Mediterranean 100 years ago were advised to stop eating carbohydrate foods if they became diabetic in their new homes. Such changes can reasonably be expected to improve longevity for the individual more often than not.
The article also mentioned the Mediterranean diet. This is not actually low in protein, nor high in carbohydrate, as far as we know. A new EPIC study shows that a high Mediterranean Diet Score (they tested 4 different Med Diet scoring systems) is associated with lower mortality in an English population (i.e. compared to the normal English diet, one shudders to think what that is today). One interesting finding is the cholesterol counts of those with low and high Med Diet Scores. Mean total cholesterol in both groups is 6.2 mmol/L, LDL is 4 and 3.9 respectively, HDL is 1.4 and 1.5, TGs are 1.9 and 1.7.
So even the high Mediterranean Diet Score consumers in the UK tend to have high cholesterol, and the diet doesn’t make a lot of difference to that, yet it reduces cardiovascular and total mortality. Interesting.
A few years ago researchers showed that cell phone radiation cures Alzheimer’s Disease in mice. I don’t remember those researchers going all over the media telling us to strap cell phones to our heads from age 50 or 60 to think better. What is it about diet researchers?
 Solon-Biet et al., Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework, Cell Metabolism (2016), http://dx.doi.org/10.1016/j.cmet.2016.09.001
 Tong TYN, Wareham NJ, Khaw K-T, Imamura F, Forouhi NG.
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population: the EPIC-Norfolk study.
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In the news recently is a review of statin benefits and side-effects in the Lancet which, using a controversial modelling method to predict population effects from the variable results of clinical trials, recommends that statins be prescribed more widely to healthy people to lower their risk of future heart attacks.
The claim is that side-effects are rare, but they seem to be more common, and more serious, in real life than Professor Rory Collins, lead author of the review, admitted when interviewed by the BBC. In our opinion, it’s not ethical to try to trivialise the side effects of any drug that can kill or cripple the people taking it, as Professor Collins did, whether or not the benefits outweigh the risks at a population level.
It’s also worth taking into account how these statin trials are typically designed and what that means for side effects, exclusion and interpretation. We’ve written about that before here.
A commenter on the What The Fat blog sent us this link to an Official Information Act request about the number of statin-related deaths and injuries in New Zealand.
Over the period 01 January 2001 through to 31 December 2014, this document details 1709 reports describing 3826 reaction terms – one report may have more than one reaction described. 21 cases resulted in an outcome of death however in 3 cases death was not related to the Statin medicine and 2 cases were unclassifiable.
So we have 1709 reports of statins causing injury, and 21 deaths of which 15 were considered to be caused by statins. No doubt there is considerable underreporting here, as many people prescribed a drug which produces adverse effects will stop taking it without telling the doctor, and many doctors will stop prescribing such a drug without reporting the incident, so these numbers will tend to represent serious cases that weren’t easily resolved.
Why do some people experience extreme toxic reactions from statins while others tolerate them? A simple explanation for some types of harm might be, that statins reduce the synthesis of cholesterol, which lowers LDL in the blood, but everyone with a raised LDL cholesterol who is prescribed statins may not have an excessive rate of cholesterol synthesis to begin with, as cholesterol synthesis is regulated by insulin. Someone with hyperinsulinaemia due to carbohydrate intolerance will tend to have an increased cholesterol synthesis, but this will often be accompanied by low or normal LDL levels. This may be why, in modern guidelines, LDL is no longer used as the sole guide to statin prescribing (the TG/HDL ratio is a better guide to insulin status).
Potentially, statins could cause enough of a cholesterol deficiency in cells to cause harm. This is how the NASA doctor Duane Graveline, who died recently, explained his own adverse reaction to statins, which caused him to suffer from amnesia. Professor Collins denies that amnesia is caused by statins; however all cases of amnesia in the New Zealand report (39) relate to the two statins, atorvastatin (Lipitor) and simvastatin (Zocor) which are fat-soluble and cross the blood brain barrier, just as Duane Graveline predicted. Of course it is likely that amnesia in elderly patients prescribed statins is often missed as a drug side-effect, with resulting under-reporting.
A more complex mechanism for harm is that statins can be metabolised to lactones in some people, and these statin lactones are three times more toxic than the statins themselves, especially to muscle cells. Statin lactones inhibit mitochondrial respiratory complex III, reducing its activity by 84% in this experimental paper, and smaller but significant reductions in CIII activity were found in muscle biopsies from patients suffering from statin myopathy.
In conclusion, we demonstrate that the Qo site of respiratory CIII is inhibited by several statin lactones and provide evidence for an association between this off-target effect and statin-induced myopathies. Consequently, polymorphisms of UGTs, the enzymes converting statin acids into lactones, and CIII could be predisposing factors in statin-induced myopathies. We showed that both G3PDH and b-oxidation stimulation can prevent statin-induced respiratory inhibition, providing a rationale for therapeutic intervention.
CIII is part of the mitochondrial electron transfer complex or ETC (also known as the respiratory complex) which is part of the machinery cells use to generate ready-use energy units (ATP) from food. Its inhibition has the effect of reducing the muscle cell’s ability to generate ATP, with apoptosis (self-destruction) of cells as an outcome. Fortunately the beta-oxidation step of fatty acid oxidation contributes to ATP through a separate mitochondrial transporter (not usually shown in diagrams, because “glucose is the most important energy source”), and this input is able to restore CIII activity – “Beta-oxidation also contributed to convergent electron flow into CIII (i.e. it stepped around the statin blockade) and reversed the effects, restoring CIII activity to 89% of normal”.
In this cell-culture experiment beta-oxidation was stimulated by adding palmitoyl-l-carnitine to the mixture; this is a molecule of saturated fat attached to a molecule of l-carnitine, which is the molecule that carries fatty acids into the mitochondria for beta-oxidation. Co-enzyme Q10 is the molecule that carries the electrons between complexes. It has been proposed that Co-enzyme Q10 and l-carnitine be used together to treat statin myopathy. However, increased beta-oxidation is also something that happens naturally in people eating the LCHF diet – it’s called fat-burning. (on the other hand G3PDH, interestingly, is activated by fructose, but also by glycerol, part of the fat molecule).
A further way in which statins can cause damage, this time to brain and nerve cells, is by inhibiting the synthesis of vitamin K2. Many plant foods contain vitamin K1, which the body converts to K2 (mostly in the liver, but also in the brain).
When this occurs in the brain the MK4 form of K2 produced is an essential co-enzyme for the synthesis of special sulfur-containing lipids called sulfatides. Low CNS sulfatide levels are associated with cognitive decline and seen in the early stages of Alzheimer’s disease.
The MK4 form of vitamin K2 is produced with the same enzyme (HMG-CoA reductase) that is targeted by statins.
From all these facts and hypotheses, we can arrive at a number of factors likely, at least in theory, to be protective to people using statins.
One is a fat-burning metabolism. Of course this is associated with low insulin levels and therefore unlikely to cause excessive cholesterol synthesis in the first place.
Another is l-carnitine. This is made in the body, but we get extra from animal foods, especially red meat. Another is co-enzyme Q10, we make this in the body but by using the same HMG-CoA reductase enzyme that makes cholesterol and vitamin K2. Co-Q10 is found in animal foods and also in vegetable oils.
Vitamin K2 is found in animal foods such as liver and eggs, in cheeses, and in other fermented foods such as natto and sauerkraut.
And cholesterol itself, of course, is only found in significant amounts in fatty animal foods, especially eggs, offal, and shellfish.
The irony is that the diet most likely to protect against statin side-effects (if that is in fact possible), is a high-fat diet with plenty of rich and tasty animal foods. Exactly the sort of diet you’ll be told to avoid by most of the doctors prescribing them.
We do have quite a few studies of carbohydrate-restricted diets in people taking statins showing that the combination is safe and results in added improvement.
In conclusion, these findings demonstrate that individuals undergoing statin therapy experience additional improvements in metabolic and vascular health from a 6 weeks CRD as evidenced by increased insulin sensitivity and resistance vessel endothelial function, and decreased blood pressure, triglycerides, and adhesion molecules.
And our favourite, the “high saturated fat and no-starch” diet.
An HSF-SA diet was prescribed for all patients; they were instructed to attempt to consume one half of all calories as saturated fat, primarily as red meat and cheese. Eggs and other low-fat forms of protein were allowed, regardless of cholesterol content. Fresh fruit and nonstarchy vegetables were prescribed in restricted amounts at each meal.
Starch was forbidden.
In patients with atherosclerotic cardiovascular disease, an HSF-SA diet results in weight loss after 6 weeks without adverse effects on serum lipid levels verified by nuclear magnetic resonance, and further weight loss with a lipid-neutral effect may persist for up to 52 weeks. All patients were obese (mean +/- SD body mass index [BMI], 39.0+/-7.3 kg/m2) and had been treated with statins before entry in the trial.
This diet contains every element that (in theory at least) should protect against statin side-effects. It’s high enough in fat and low enough in carbohydrate to stimulate beta-oxidation (and even supplies some fructose to activate G3PDH), it supplies vitamin K2, l-carnitine, Co-enzyme Q10 and cholesterol.
Take home points
- Statins inhibit the synthesis of cholesterol, excessive production of which is an effect of high insulin levels. Therefore, if statins do reduce heart attack risk, diets which lower insulin secretion by restricting carbohydrate should do so too. However, statins are only specific for one effect of excess insulin, whereas carbohydrate restriction reduces its effect on multiple pathways.
- Statins can damage muscles, with life-altering consequences, by inhibiting the mitochondrial CIII complex involved in the production of energy (ATP). Diets which activate fat-burning in muscles by restricting carbohydrate can restore energy production (in theory, based on experimental evidence).
- Statins can cause memory loss and neuropathy, probably by depleting vitamin K2 and cholesterol in the brain and nerves. High-fat, animal based diets are good sources of these nutrients, and also supply extra l-carnitine and Co-enzyme Q10 that may help to protect muscles.
As always, we are not cardiologists and are not qualified to prescribe statins or advise against using them. Those are decisions for your doctor and you (yes you!) to make when you weight up the likely benefits and harms and what weight to give to all of these combined.
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 Effect of a high saturated fat and no-starch diet on serum lipid subfractions in patients with documented atherosclerotic cardiovascular disease.
Hays JH1, DiSabatino A, Gorman RT et al.
Mayo Clin Proc. 2003 Nov;78(11):1331-6.
In the latest Lancet, Yoni Freedhoff and Kevin Hall have an opinion piece about diet trials, in which they argue that it’s not helpful to know that an ad lib low-carb diet results in more weight loss than a calorie-restricted low-fat “dietary guidelines” type diet, because the weight loss differences are not clinically significant, a claim which we think is both false, and overlooking other benefits of carbohydrate restriction.
They then go on to ask that more effort go into identifying ways to ensure that people can adhere to diets long term, a reasonable request and something we’re very much interested in ourselves. However, they spoil this a bit by talking about “hype” (short for hyperbole) and “society’s endless parade of fad diets”. If you want to improve adherence to diets and you think that there is little to choose between them, why use the word “fad”, which is normally used to devalue people’s dietary choices?
Further, is there even an endless parade of diets these days? Aren’t there a just few variations on and recombinations of the same timeless themes, such as vegan or vegetarianism, calorie restriction, carbohydrate restriction, ancestral, and so on? The only really original idea is fasting, yet this ancient therapy only seems original because we’ve just been led through such an intensive era of round-the-clock eating.
Freedhoff and Hall concentrate their argument on one trial, the DIRECT study (sometimes better known as Shai et al.) which was a 24-month workplace intervention in Israel, with ad lib low-carb, low-fat calorie restricted, and Mediterranean diet calorie restricted arms. “The low-carbohydrate, non–restricted-calorie diet aimed to provide 20 g of carbohydrates per day for the 2-month induction phase and immediately after religious holidays, with a gradual increase to a maximum of 120 g per day to maintain the weight loss…the [low carb] participants were counseled to choose vegetarian sources of fat and protein and to avoid trans fat. The diet was based on the Atkins diet.” The Mediterranean diet (at 40% fat, mainly from olive oil and nuts) was based on a 2001 book by Walter Willett and PJ Skerrett, and the low-fat diet was based on American Heart Association dietary guidelines. All dieters had access to the same food in the workplace cafeteria, but the food suitable for each different diet was colour coded.
In this study, people in the low carb group (not very low carb after induction, it varied between 87g/day at 6 months and 120g/day reported CHO intake over the first 12 months) lost on average 1.8 Kg more weight than the low fat dieters overall.
Well as Freedhoff and Hall say, that’s not a lot of weight in the grand scheme of things. So does it support their claim that we should stop caring about the results of these studies?
Not so fast. The average weight loss includes all the people who drop out of the study; this is “intention to treat” (ITT) analysis, designed to keep the randomisation of baseline characteristics stable.
But what you might want to know if you were choosing a weight-loss diet, is, what will happen to me if I follow the diet? There were more drop-outs (22% vs 10%) in this study in the low carb arm, who found it hard to resist the biscuits and cakes in the cafeteria (interestingly, this caused their intake of saturated fat to increase over the study, even as their total fat intake went down), and self-reported complete adherence to low-carb was 57% at month 24. The superiority of the low carb diet in DIRECT includes the effect of including this higher drop-out rate, and those extra cakes and biscuits. The per-protocol analysis only gives us a stratified comparison of completers vs non-completers (i.e. minus drop-outs, but including those with weak adherence to diets) at 24 months, but we do know from other studies that when non-completers are excluded, the long-term difference between diets at 12 months becomes larger.
So compliance is important, sticking to the diet is critical of course, but what diet you stick to matters more than Freedhoff and Hall are saying. In the DIRECT study, people who completed 24 months of the low-carb diet lost a mean 5.5 +/- 7.0 Kg, and those who completed the low fat diet lost 3.3 +/- 4.1 Kg. The biggest loser in the DIRECT study lost 35% of their body weight, but all we know about the most successful dieters is, that they weighed more at baseline, lost weight more rapidly in the early stages, and ate a bit less protein and cholesterol at baseline (but overall the protein intakes in this population were, and remained, quite high). Rapid weight loss early in a diet is usually associated with success, and of course it’s a feature of the ketogenic diet, or the induction phase of the Atkins diet here.
But wait, there’s more. Weight loss isn’t the only effect of diet, and overweight people often suffer from increased cardiometabolic risk owing to insulin resistance and the metabolic syndrome.
Freedhoff and Hall for some reason don’t mention this, but it’s the evidence we have about the “long term safety” of any diet. In all parameters the ad lib low carb diet does better than the calorie-restricted low-fat diet, even at 24 months, and even including the drop-outs.
“Among the participants with diabetes, the proportion of glycated hemoglobin at 24 months decreased by 0.4±1.3% in the low-fat group, 0.5±1.1% in the Mediterranean-diet group, and 0.9±0.8% in the low-carbohydrate group. The changes were significant (P<0.05) only in the low-carbohydrate group (P=0.45 for the comparison among groups).” In fact, as far as we know, carbohydrate-restricted diets are the only diets that can produce some of these benefits without weight loss.
There’s a curious extra point in the chart below – LDL rose slightly at 6 months in the low-carb arm, when adherence was good and polyunsaturated fat intake was high, and dropped at 24 months when polyunsaturated fat intake decreased and carbohydrate, but also saturated fat, intake increased.
But wait, there’s more. Something else that Hall and Freedhoff didn’t mention is the very long-term effects of this diet trial, because there was a four-year follow-up study. And the results here are very interesting, because there is less of a rebound effect for the ad lib low carb diet and the Mediterranean diet than for the low-fat, calorie restricted AHA diet.
In the low-fat diet group (which had the fewest drop-outs) most of the improved metabolic parameters, including weight, are back to baseline levels. In the low-carb group, weight and the LDL/HDL cholesterol ratio are still improved. This is four years after the end of a 2-year study – six years in all. Quite a different result from Hall’s Biggest Loser study, where severe rebound weight gain from CICO “eat less move more” energy restriction was the order of the day.
After the completion of intervention, the participants were invited once a year to the clinic for a regular check-up and were encouraged to pursue a healthy diet. Although diet-group color coding and nutrition labeling in the workplace cafeteria were stopped at the end of the intervention, the cafeteria continued to serve suitable meals according to the guidelines of the 3 diets, suggesting that the workers could still consume their specific dishes, which continued to be regularly served, as they were during the trial. We did not continue with the dietary sessions or any other activity encouraging adherence. We used one question: Are you still dieting? The question had three possible answers to choose from: 1. “Yes, with my original diet” 2. “Yes, but I switched to another diet” 3. “No, I am not dieting”. No differences were observed in response to this question between the 3 assigned diet groups (p=0.36).
Perhaps there are a few people in this group who were so happy with their results that they stuck with the low-carb diet for 6 years, and their results are carrying the rest – or perhaps the 2 years of low-carb diet (or the 2 months of ketogenic dieting) had lasting benefits. These questions weren’t really answered by the questionnaire quoted above, which kind of refutes Freedhoff and Hall’s suggestion that we have nothing more to learn from diet comparisons. Good post hoc analysis of the data from weight loss trials can seek to develop further hypotheses about what baseline markers, characteristics, and responses predict success, and that should inform the design of further trials and interventions. It’s also possible to tweak the diets to improve them for both effect and ease of compliance – (e.g. what if the AHA diet had been lower-GI, the Med diet lower carb, and the low-carb diet lower carb, with more Mediterranean and real food elements? Something like this probably went on during the 4-year follow-up among the people still interested in the diets).
But in the meantime, we needn’t let ourselves get confused about how to proceed.
As Prof Richard Feinman says, “remind me again why we have a medical science literature?” Comparative trials of diets and drugs are designed and published so that we know what is the most effective option between two or more choices for any given diagnosis. The intention is that the best treatment, determined by experiment, will be the one to be offered first. The patient may not like it, or it may not work, in which case it will be time to try something else, but the evidence is there to inform the discussion.
Instead we are stuck in this Catch 22 where the evidence about the best treatment for overweight and diabetes, collected over decades at great expense, is ignored (or worse) because its results contradict cherished beliefs about (in this case) the pre-eminence and equivalence of the calorie, or (at other times) the health effects of saturated fat.
Fortunately some people are brave enough to follow the existing evidence while applying themselves to solving the question of adherence. David Unwin and colleagues in the UK have worked on the psychological aspects of motivating and supporting people in low carb diets for type 2 diabetes and NAFLD with great success, and recently a multicenter LCHF approach in Canada has also reported good adherence and impressive results.
A thought experiment
The DIRECT study had no control group, i.e. no group of people from the same population eating a normal (whatever they are normally eating) diet ad lib.
Imagine there was a fourth arm randomised to an ad lib version of one of the 3 diets.
Without calorie restriction, it seems less likely that the AHA-approved, last-year’s dietary guidelines diet would have made any difference from baseline. It’s possible that nothing would have improved and plausible that things would have continued to get worse overall.
Without calorie restriction, it’s likely that the Mediterranean diet (the modern, updated dietary guidelines diet) would still have been better than the AHA-approved, last-year’s model dietary guidelines diet.There may well have been some smaller improvements, and things would be unlikely to get worse.
Now imagine an ad lib version of the LCHF diet (the controversial, alternative-dietary guidelines diet). The results would still be exactly the same, because the experimental diet was ad lib.
 Freedhoff Y, Hall KD. Weight loss diet studies: we need help not hype. The Lancet , Volume 388 , Issue 10047 , 849 – 851.
 Shai, I, Schwarzfuchs, D, Henkin, Y et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008; 359: 229–241
 Greenberg, I, Stampfer, MJ, Schwarzfuchs, D, and Shai, I. Adherence and success in long-term weight loss diets: the dietary intervention randomized controlled trial (DIRECT). J Am Coll Nutr. 2009; 28: 159–168
 Feinman RD. Intention-to-treat. What is the question? Nutr Metab (Lond). 2009 Jan 9;6:1. doi: 10.1186/1743-7075-6-1. Full text:
 Gannon MC, Nuttall FQ. Control of blood glucose in type 2 diabetes without weight loss by modification of diet composition. Nutrition & Metabolism 2006 3:16 DOI: 10.1186/1743-7075-3-16. Full text:
 Schwarzfuchs D, Golan R, Shai I. Four-year follow-up after two-year dietary interventions. N Engl J Med. 2012 Oct 4;367(14):1373-4. doi: 10.1056/NEJMc1204792.
Full text: http://www.nejm.org/doi/full/10.1056/NEJMc1204792
 Fothergill, E, Guo, J, Howard, L et al. Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity (Silver Spring). 2016; DOI: http://dx.doi.org/10.1002/oby.21538 (published online May 2.)
 Unwin DJ, Cuthbertson DJ, Feinman R, Sprung VS (2015) A pilot study to explore the role of a low-carbohydrate intervention to improve GGT levels and HbA1c. Diabesity in Practice 4: 102–8. Full text:
 Mark S, Du Toit S, Noakes TD, Nordli K, Coetzee D, Makin M, Van der Spuy S, Frey J, Wortman J. A successful lifestyle intervention model replicated in diverse clinical settings. S Afr Med J. 2016 Jul 3;106(8):763-6. doi: 10.7196/SAMJ.2016.v106i8.10136.
full text: http://samj.org.za/index.php/samj/article/view/10136/7528
On the Sunday current affairs program in New Zealand there was a report on the diabetes epidemic in South Auckland. This is our largest (and growing) health problem, and two of the players in this tragedy had messages that stood out. An elderly woman, overweight and now condemned to thrice-weekly dialysis, told us “I didn’t do anything wrong”.
How right she was. The Ministry of Health website still offers this “healthy eating” advice – “Fill up on breads, cereals, pasta and rice.”
Junk epidemiology and junk food
The epidemiologists from Harvard recently grabbed headlines with claims that polyunsaturated fats are the healthiest fats, that chicken is one of the healthiest animal proteins, and that plant proteins are healthier than animal proteins. In South Auckland, a staple food is Kentucky Fried Chicken. Chicken is a meat naturally high in polyunsaturated fat, KFC is fried in “healthy” polyunsaturated vegetable oils, and therefore a good source of these, and it even comes with a bean salad – plant protein. This junk food meal, eaten wherever diabetes is rampant (the franchise only came to New Zealand in the 1970’s), actually ticks most of the boxes thrown up by junk epidemiology.
With this sort of dangerous misinformation on official government websites and in the media, how can anyone know what is “right” or “wrong” when it comes to their risk of type 2 diabetes?
The look of success?
One chap in the Sunday program, Kim, had it figured out. He’d reversed his diabetes by, firstly, losing weight rapidly on a low calorie diet (like the Newcastle diet, but with real food instead of Optifast), by exercising regularly, and by eating a diet described as “lots of vegetables” – we saw a delicious looking stir-fry – “no bread, potatoes, rice, pasta” – he didn’t even need to mention sugar.
Incidentally, what is a “fast-acting” carbohydrate? Previously, it was assumed that fast-acting carbohydrates were sugars or juices. It is now known that this is not true, and if there were a fast-acting carbohydrate, it would probably be a starch. “Fast-acting carbohydrate” is a term we need to eliminate from our diabetes vocabulary. – Marion J. Franz, MS, RD, LD, CDE
“So what’s left?” asked the interviewer. “Eggs, meat?” “You’d be surprised how much there is left that’s good to eat!”
Now, the direct end result of type 2 diabetes is a series of complications which include cardiovascular disease, retinopathy, neuropathy, kidney disease and gangrene (caused when vascular damage cuts of blood supply to the extremities, usually the feet, compounded by neuropathy preventing pain warning of injury, and infections fed by high sugar levels and suppressed immune function). Gangrene often requires the amputation of the affected parts, and the surgeon who has to perform this procedure is an orthopedic surgeon.
The case of Dr Gary Fettke
Gary Fettle is a friend of mine. He’s also an orthopedic surgeon in Tasmania, Australia who performs dozens of these operations on patients with type 2 diabetes every year. “I used to do one amputation every 6 to 12 months and now I’m doing one a week”. Seeing, as anyone can who has eyes in their head, the link between diet and diabetic blood sugars and the risk of complications (hardly controversial), he had dared to make a study of nutrition and diabetes literature – something which, as a highly trained medical professional, he was well able to do – and advise his patients, and the public, about how to eat to beat, and avoid type 2 diabetes and/or its complications.
Now Dr Fettke has been banned from giving any diet advice, to patients or in any media, until further notice.
Why? What he is advising is plainly good sense as well as evidence-based. It’s the same message Kim gave on the Sunday program, except that Dr Gary Fettke is a highly trained medical professional with hundreds of hours of clinical experience.
Here’s a great response to the silencing of Dr Fettke, written by Tyler Cartwright for the Ketogains website, that puts the case better than we can.
Meanwhile the Australian authorities continue to allow Associate Prof Sof Andrikopoulos to give diet advice, despite his telling the Australian public to eat sugar with burgers – based on his experience with mice. (I guess that also makes the soft drinks at KFC part of the healthy menu now).
Gary’s not the first and won’t be the last
In 2005 the Swedish dietetics authorities tried to silence Dr Annika Dahlqvist. Their heavy-handed actions led to a court case in 2008 which Dr Dahlqvist won, publicising the benefits of LCHF all over Sweden, and as a result a significant proportion of the Swedish population soon knew about the diet, and butter sales went up – leading to much hand-wringing around the world among people committed to outdated bad advice, but no adverse effects in the Swedish population – according to the Swedish government’s health data base, heart attacks are now at an all-time low.
Heart attacks in Sweden by year, 2006-2014.
In this recent Australian TV series, The Saving Australia Diet, Dr Fettke is seen advising the patient Tony on how to treat diabetes with the LCHF diet, with the help of chef Pete Evans. For no good reason that we can see, other than some virulent local strain of the Tall Poppy syndrome, the Australian establishment hates Pete Evans, and this has made some scientists who should know better indulge in bottom-of-the-barrel stunts like Ass Prof Sof Andrikopoulos’s “Paleo mouse” attacks on low carbohydrate diets. It is almost certainly his association with Pete Evans that has drawn the complaint that has led to Dr Fettke being silenced.
Of course, this kind of heavy-handed, bloody-minded action is only possible because Dr Fettke is a health professional, and therefore subject to the discipline of a regulatory body, even if it is being abused for unworthy personal ends and is clearly not in the public interest. Pete Evans, on the other hand, is a member of no such body, so he can’t be silenced, thank goodness.
This is why it’s important for everyone who speaks on nutrition to have a proper qualification – so they can be silenced when they embarrass the authorities, for example by being right about something the government and its appointed experts have been consistently wrong about. Especially in the middle of an epidemic, when damage control is the order of the day.
Well, here’s an idea – instead of “damage control” being about saving reputations, can’t we have damage control that will mean saving feet, eyes, and kidneys?
We don’t always say good things about Aussies (us New Zealanders, and vice versa), but they are our mates really and Gary Fettle is one of the good ones. Shame on you Australia and the Australian Medical Authorities for allowing this to happen.
We are doing a seminar Sept 8th, AUT Millennium Auckland
Presenters – me (Grant Schofield), dietician Dr Caryn Zinn, and Jimmy Moore all the way form the USA talking about his experiences with fasting.
It’s definitely an intro night, so well suited to those just getitng into or supporting others getting into this lifestyle
Limited space – book online here
- Date: Thursday 8th September
- Location: AUT Millennium, The Finish Line,
- 17 Antares Place,Mairangi Bay, Auckland
- Time: 6.30pm –8.30 pm
- Tickets: $25, limited to the first 150 people
- Buy your tickets online at shop.autmillennium.org.nz
- Sorry no door sales
PDF flyer here MIL154729 HPC Flyer 8.9.16 2
This (very technical) paper has made a big splash on the internet and in the media, not just in New Zealand but all around the world.
A thrifty variant in CREBRF strongly influences body mass index in Samoans
Ryan L Minster, Nicola L Hawley, Chi-Ting Su, Guangyun Sun, Erin E Kershaw, Hong Cheng, Olive D Buhule, Jerome Lin, Muagututi‘a Sefuiva Reupena, Satupa‘itea Viali, John Tuitele, Take Naseri, Zsolt Urban, Ranjan Deka, Daniel E Weeks, & Stephen T McGarvey
Nat Genet. 2016 Jul 25. doi: 10.1038/ng.3620. [Epub ahead of print]
Samoans are a unique founder population with a high prevalence of obesity, making them well suited for identifying new genetic contributors to obesity. We conducted a genome-wide association study (GWAS) in 3,072 Samoans, discovered a variant, rs12513649, strongly associated with body mass index (BMI) (P = 5.3 × 10−14), and replicated the association in 2,102 additional Samoans (P = 1.2 × 10−9). Targeted sequencing identified a strongly associated missense variant, rs373863828 (p.Arg457Gln), in CREBRF (meta P = 1.4 × 10−20). Although this variant is extremely rare in other populations, it is common in Samoans (frequency of 0.259), with an effect size much larger than that of any other known common BMI risk variant (1.36–1.45 kg/m2per copy of the risk-associated allele). In comparison to wild-type CREBRF, the Arg457Gln variant when overexpressed selectively decreased energy use and increased fat storage in an adipocyte cell model. These data, in combination with evidence of positive selection of the allele encoding p.Arg457Gln, support a ‘thrifty’ variant hypothesis as a factor in human obesity.
This is a big deal because the thrifty gene hypothesis – that some people are prone to obesity because their ancestors evolved to store energy more effectively in times of plenty – had been dead in the water for lack of convincing evidence. Genes are complicated things and previous studies hadn’t turned up anything with this sort of effect size (obesity is common today, yet these “thrifty” genes are normally quite rare). The thinking is that the gene variant (technically a “missense” mutation where a particular amino acid in a protein has been replaced with a different amino acid that reduces its function) was selected for during long sea voyages, where starvation and hypothermia weeded out individuals who had been less effective at storing and/or holding onto fat.
These genes are not destiny
Stephen McGarvey, the senior author, was quick to point out in all his interviews that this genetic evidence doesn’t mean that such genetics destine Pasifika people to be obese independently of environment, that is, diet, lifestyle, and exercise. (Though the study only looked at Samoa, it is almost certain that the gene will be found to be similarly common in other Pasifika populations). It is unlikely that the va’a tele or waka that carried the Polynesian explorers round the Pacific basin carried any obese individuals even when they set out; the stored energy advantage that the gene variant gave in these times was probably a few Kg and barely noticeable. If we look online for historical photographs of Samoa, we find that Samoa has a rich political history – it was the meeting place of the German, British, and U.S. Empires in the late 19th century – which resulted in much photographic documentation. But even as recently as 1930, during the period of the Mau independence movement, there is no evidence of obesity in photos.
These are pupils of Vaipouli school, a Samoan secondary school, ca 1930.
And these (photo at top) are leaders of the Mau movement at the same time.
Regardless of genetics, indigenous populations rarely if ever experience obesity eating their traditional diets, and always experience a high rate of obesity and/or diabetes, as well as the other diseases of Western civilisation (tooth decay, heart disease, cancer, appendicitis), after transitioning to Western processed and refined foods – foods with a high Human Interference (HI) factor. Traditional Samoan staple foods are taro and coconut, breadfruit and banana, turtle, pork and fish; this is never a question of fat vs carbs, or of saturated fat vs unsaturated fat, nor even of fructose vs glucose (the Ti root prepared in much of polynesia is very high in fructose) – it’s a question of natural foods with their fibre, micronutrients, fats and protein intact, vs refined starch, sugar, and refined oils, including the soybean oil used to pack canned fish in the case of Polynesia.
Obesity prevents diabetes? Come again?
A really interesting finding from this study from our point of view is that the “obesity” gene variant is strongly protective against type 2 diabetes.
Higher BMI and adiposity are usually associated with greater insulin resistance (higher fasting insulin levels and homeostatic model assessment–insulin resistance (HOMA-IR)), an atherogenic lipid profile (especially higher serum triglyceride and lower HDL cholesterol levels), and lower adiponectin levels. We therefore expected the BMI-increasing A allele of rs373863828 to also be associated with these metabolic variables. However, even though the A allele was consistently associated with higher BMI and adiposity in both the discovery and replication cohorts, the expected associations with the above obesity-related comorbidities were not observed and, in some cases, were even in the opposite direction to that expected (Table 2 and Supplementary Table 2).
Notably, when considering all subjects, the risk of diabetes was actually lower (OR = 0.586 for the discovery cohort, P = 6.68 × 10−9) or trended lower (0.742 for the replication cohorts, P = 0.029) in carriers of the A allele. Likewise, even in non-diabetic subjects, the variant was associated with moderately but significantly lower fasting glucose levels in both the discovery and replication cohorts (1.65 mg/dl (P = 9.5 × 10−5) and 1.54 mg/dl (P = 8.8 × 10−4) lower for each copy of the A allele, respectively). These effects became even more significant after adjusting for BMI (2.25 mg/dl, P = 6.9 × 10−8 and 2.09 mg/dl, P = 7.6 × 10−6), suggesting an independent effect of the variant on glucose homeostasis and diabetes risk.
How can this be? Obesity is associated with, and plausibly causal in, diabetes, yet a gene variant that increases obesity halves the rate of diabetes?
This is in fact strongly supportive of the ectopic fat hypothesis of diabetes causation, and the personal fat threshold hypothesis of Professor Roy Taylor of Newcastle Diet fame.
“We hypothesize that each individual has a personal fat threshold (PFT) which, if exceeded, makes likely the development of T2DM. Subsequent weight loss to take the individual below their level of susceptibility should allow return to normal glucose control. Crucially, the hypothesized PFT is independent of BMI.”
“A key reason for the greater increase in diabetes risk per unit increase in BMI in South Asians compared with Europeans may be due to a reduced capacity in South Asians to store fat in the primary superficial subcutaneous adipose tissue compartment, leading to earlier `overflow’ into secondary deep subcutaneous and visceral fat compartments, and potentially the liver.” 
(Professor Taylor’s research also pinpoints the pancreas as a target for this “overflow”).
Imagine the body as a house in which rainwater (energy stored as fat) is collected in a tank; if the water is not used, and the tank fills, the water will overflow into the walls and floors of the house; the house will be at risk of rotting and the electrics might short out. The larger the tank, the less risk of damage there will be in a downpour. But no matter how big the tank, the house can still be damaged if it fills to overflowing. This tank is the capacity to store energy (fat, and the fat produced from carbohydrate) subcutaneously (in the folds of fatty tissue under the skin).
So it is not a paradox that while weight gain increases the risk of type 2 diabetes, some of the people who are most prone to obesity for genetic reasons will have a lower risk of type 2 diabetes at a given BMI.
1) about 1 in 4 people in Samoa, and possibly similar numbers in other Pacific populations, have a variant gene that makes it easier to store fat and become obese. This strengthens the “thrifty gene” hypothesis of obesity, at least with regard to these populations.
2) This gene is also associated with a significantly reduced risk of diabetes, a fact which strengthens the “ectopic fat” and “personal fat threshold” hypotheses of type 2 diabetes.
3) Variant genes or their lack did not result in obesity or diabetes in Samoan populations living their traditional lifestyles and eating their traditional diets of unrefined, nutritious animal and vegetable foods. Western processed foods and refined high-energy ingredients have been a disaster for these peoples. This strengthens the “gene – environment mismatch” theory of modern diseases, and the Paleolithic diet hypothesis.
 Behavioral risk factors for obesity during health transition in Vanuatu, South Pacific.
Kelsey Needham Dancause, Miguel Vilar, Michelle Wilson, Laura E Soloway, Christa DeHuff, Chim Chan, Len Tarivonda, Ralph Regenvanu, Akira Kaneko, J Koji Lum, and Ralph M Garruto. Obesity (Silver Spring). 2013 Jan; 21(1): E98–E104. (full-text link)
 Normal weight individuals who develop Type 2 diabetes: the personal fat threshold. Roy Taylor, Rury R. Holman. Clinical Science Apr 01, 2015, 128 (7) 405-410; DOI: 10.1042/CS20140553
 Type 2 diabetes as a disease of ectopic fat?
Naveed Sattar and Jason MR Gill. BMC Medicine 2014:12(123) (full-text link)