By George Henderson and Grant Schofield
There are few diet trials published from New Zealand, so we’re always keen to see them; and there are even fewer vegan diet trials.
We are even more interested when they go beyond their data, and start in on a sort of zealot approach to running down low carb diets which this study gives no insight into.
So what did they do? They went vegan (plant only) That is, we think this was a vegan study, because it’s called a “whole food plant based diet”, well-known vegan doctors are cited in the supplementary materials, dietary fat intakes were, though not measured, intended to be very low indeed, and because B12 supplements were supplied, but few details about the intervention are given, and even fewer about the controls; these received “standard medical care” with no diet advice mentioned.
The study was small (n=65) and not as representative as the authors might have hoped for; “The intervention involved patients from a group general practice in Gisborne, the region with New Zealand’s highest rates of socioeconomic deprivation, obesity and type 2 diabetes” – however, after randomisation there were only 3 Māori with 30 NZ European in the intervention arm (n=33) whereas the control arm had 21 European, 5 Māori and 6 other (n=32).
The results were excellent in terms of weight loss, and good in terms of medication reduction, with a couple of people reversing diabetes. Weight lost was as great as in the best ketogenic diet trials, although the controls here, with no diet change (or else useless advice based on NZ government recommendations? It would be good to know) provided no competition.
“The mechanism for this is likely the reduction in the energy density of the food consumed (lower fat, higher water and fibre). Multiple intervention participants stated ‘not being hungry’ was important in enabling adherence.” In other words, de facto calorie restriction is likely to have occurred, due to greater satiety per calorie, the same as mooted in LCHF studies.
The weight changes at 3 months don’t compare too badly with the weight changes at 10 weeks in the first report from this long term ketogenic diet study.  The reductions in medication and reversals of diabetes are greater in the ketogenic diet study, with a similar intensity of intervention, but nonetheless the BROAD weight loss results are very good by the standards of most diet trials.
So the Whole food plant-based (WFPB) diet didn’t do too badly for weight loss; what about other parameters?
In our opinion this is where the BROAD study lets itself down; it’s not that these results are terrible, but that the discussion of them, such as it is, amounts to special pleading. HDL was low (“high risk”) at baseline – 1.3 mmol/l in the intervention arm; HDL didn’t change, but the TG/HDL ratio deteriorated from 2.835 to 3.170.
“CVD Risk Assessment tools are widely used in New Zealand, and although we saw intervention WC, BMI and HbA1c improve, the between-group CVD RA (which does not account for some of these) did not change significantly. Also, HDL-cholesterol tends to decrease on a plant-based diet, and previous research had shown this ‘may not be helpful for predicting cardiovascular risk in individuals consuming a low-fat, plant-based diet’. Our analysis corroborates that this tool is not particularly appropriate for those consuming a WFPB diet.”
Now, this may well be true, but the reference for this claim is one 30-day cohort study (no comparison arm) using the same kind of wishful thinking. What would be more convincing would be a mechanistic explanation of why lower HDL levels are tolerable on a very low fat diet, maybe through the diet’s effect on HDL subtype, or HDL efflux capacity, or an interaction with very low LDL, demonstrated in feeding studies. However, LDL in the intervention arm was 3 mmol/l at 12 months which though almost within target is not especially low, and the TG/HDL ratio predicts that the percentage of small dense LDL will be relatively high, so we do need more than wishful thinking before discounting the relevance of these scores. If we were to claim that a lack of effect on LDL didn’t matter in a low carb study, we would have no shortage of mechanistic evidence from feeding studies and risk factor studies to explain why; there is a huge body of scientific investigation about lipoproteins that can be relevant to these sorts of cases.
Where the discussion goes badly wrong is in attacking LCHF diets using evidence that is thin and irrelevant. The numbers of people in LCHF trials and feeding studies has become large enough that patterns of adverse outcomes can be decided by the evidence from these studies. As prior to recent years very few people in the general population ate LCHF diets, epidemiological studies don’t give us this evidence.
So what do we get, by way of a discussion of superiority?
Reviews comparing the WFPB approach to other diets show similar weight loss at 12 months for low-carbohydrate and low-fat diet approaches. However, studies on the effects of low-carbohydrate diets have shown higher rates of all-cause mortality,54 decreased peripheral flow-mediated dilation,55worsening of coronary artery disease,56 and increased rates of constipation, headache, halitosis, muscle cramps, general weakness and rash.
This isn’t good enough. Reference 54, Noto et al, is a notorious mishmash of epidemiological studies, uses an idiosyncratic and unrealistic scoring system, is mostly concerned with protein (or at least certainly conflated with it), and includes no evidence from low carbohydrate diet trials. In fact, because more recent evidence shows that higher fat intake was associated with lower mortality in the Nurses Health Study and Health Professionals Follow up Study, and lower cardiovascular mortality in the Malmo Diet and Cancer study, not to mention the forthcoming PURE study, this line of evidence, even were it admissible, is no longer supportive of the claim. Reference 55 combines 5 studies only one of which had significant results – in any case, FMD is an insulin-mediated response to glucose in the bloodstream and its reduction, while possibly undesirable and indicative of insulin resistance on a high-carb diet, would seem to be a normal adaptation to the absence of carbohydrate. Reference 56 relates to people eating high protein during an uncontrolled low fat, high carbohydrate intervention – how high, and what else did they eat differently? It’s impossible to tell from the paper, which is a singularly inappropriate piece of evidence to use in an attack on low carb.
What about “increased rates of constipation, headache, halitosis, muscle cramps, general weakness and rash”? Some of these are expected temporary effects of keto-adaptation or of insufficient salt intake during low-carb induced natriuresis. Rash can result from increased intake of unrefined plant foods in people who are salicylate-intolerant, so is a possible side effect of vegan diets too.
The greatest weakness of this paper is its failure to discuss at all two findings; firstly that blood pressure increased on the WFPB diet. This was not statistically significant (p=0.06) but as it is an underpowered trial and this result ran counter to expectations it is worth explaining; possibly a reduction in medication can account for it.
Secondly, one person in the intervention arm had their gallbladder removed due to gallstones at 5 months. This is a known adverse effect of weight loss on a very low fat diet.[4,5] It was the subject of a 2014 meta-analysis, which found that “diets high in fat content reduced gallstones, compared with those with low fat content (risk ratio, 0.09; 95% CI, 0.01-0.61)”. This would seem to be more serious than the known side effects of low carb diets. Though the one event of this sort in BROAD cannot be statistically significant, the authors (and reviewers) should have been aware of similar occurrences in other trials, making this an important risk to discuss.
Adherence at 12 months was 70% but no-one’s reason for dropping out was given.
(The informed consent phase meant that people who agreed to be in the study were aware that a vegan diet would be the only diet they were likely to get. This could be seen as a different situation in terms of self-selection bias from those studies which offer an equal chance of getting a low carb diet or a calorie-restricted 30% fat diet; people who didn’t specifically want a vegan diet could opt out, knowing their care would be the same, whereas with a two-diet comparison people may be more likely to enter the study but drop out after learning what diet they have been randomised to.)
Although this study obtained very good results in terms of weight loss, a definite win for its participants, the authors’ unwillingness to discuss possible negatives and their over-eagerness to attack low carb interventions without real evidence (they should have saved their bile for the “usual medical care” that failed their patients) do not enhance this paper’s value.
Nor does the appeal to the environmental sustainability and greenhouse gas footprint, which depends on a 2014 UK modelling paper. It all depends what foods you eat – at present these models use the lean meat, low fat dairy recommendations; however, animal fat and organ meat are wasted products, adding up to a lot of energy and nutrition, of producing these that we could use a lot more wisely. A vegan diet will have a larger environmental impact if you need to eat more imported food and out-of-season (not a problem with NZ beef and lamb) and food with a higher water content, which isn’t a very economical use of land. Raising monoculture plant crops uses more fossil fuels and has a worse effect on the land than raising ruminants the way we do in New Zealand (something you might miss with a UK model, where a lot of meat is imported). It is early days for that kind of research and all we have so far is speculative models based on assumptions.
Take homes? This trial tells us little about eating meat. It shows that getting off sugar, and refined foods has a good effect on short and medium term weight loss on this intensive intervention group compared to usual care. However an effect may be the worsening of some CVD risk factors, although what this really means isn’t clear. It says nothing about low carb healthy fat eating.
 Wright N, Wilson L, Smith M, Duncan B, McHugh P. The BROAD study: A randomised controlled trial using a whole food plant-based diet in the community for obesity, ischaemic heart disease or diabetes. Nutrition & Diabetes. 2017; 7(e256) doi:10.1038/nutd.2017.3. http://www.nature.com/nutd/journal/v7/n3/full/nutd20173a.html
 McKenzie AL, Hallberg SJ, Creighton BC, Volk BM, Link TM, Abner MK, Glon RM, McCarter JP, Volek JS, Phinney SD
A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes
JMIR Diabetes 2017;2(1):e5. DOI: 10.2196/diabetes.6981
 Kent L, Morton D, Rankin P, et al. The effect of a low-fat, plant-based lifestyle intervention (CHIP) on serum HDL levels and the implications for metabolic syndrome status – a cohort study. Nutrition & Metabolism. 2013;10:58. doi:10.1186/1743-7075-10-58.
 Festi D, Colecchia A, Orsini M, et al. Gallbladder motility and gallstone formation in obese patients following very low calorie diets. Use it (fat) to lose it (well). Int J Obes Relat Metab Disord. 1998; 22(6):592-600.
 Gebhard RL, Prigge WF, Ansel HJ, Schlasner L, Ketover SR, Sande D, Holtmeier K, Peterson FJ. The role of gallbladder emptying in gallstone formation during diet-induced rapid weight loss. Hepatology. 1996; 24(3):544-8.
 Stokes CS, Gluud LL, Casper M, Lammert F. Ursodeoxycholic acid and diets higher in fat prevent gallbladder stones during weight loss: a meta-analysis of randomized controlled trials. Clin Gastroenterol Hepatol. 2014 Jul;12(7):1090-1100.e2; quiz e61. doi: 10.1016/j.cgh.2013.11.031. Epub 2013 Dec 7.
In our last post, we went into a lot of detail about specific types of saturated fat and their effects on HDL. Here, we’ll try to summarise that information, and highlight some interesting conclusions, in simpler language.
But first, a short chemistry lesson. Nothing too hard, hopefully – we’ll just focus on the main dietary saturated fats (technically, fatty acids), the 4 “even numbered, long-chain saturated fats”.
Lauric acid – a 12 carbon saturated fat (C12:0). This is the rarest of these 4 fats. It is mainly found in the diet in coconut oil (49% lauric acid) and dairy fat. Lauric acid also has some properties of the shorter medium-chain fats (C6:0 – C:10:0), making it especially ketogenic.
Myristic acid – a 14 carbon saturated fat (C14:0). This is found in coconut oil, palm kernel oil, dairy fat, and the fats of ruminants and fish.
Palmitic acid – a 16 carbon saturated fat (C16:0). This is the most common of the saturated fats, and the second most common fat in nature after oleic acid (C18:1, a monounsaturated fat). It is found in all fats and oils.
Stearic acid – an 18 carbon saturated fat (C18:0). This is the second most common saturated fat, and is found in animal fats, cocoa butter, and palm oil.
The reality is that dietary fats, as they occur in actual foods, contain combinations of lots of different fatty acids; saturated, polyunsaturated, and monounsaturated. More, within each group they contain different combinations of each sort.
For example here’s what is in beef fat and butter*
These fats are also made in the body; they can be made from glucose and other sugars, and a shorter fat can also be converted to a longer one. Thus, palmitic acid (C16:0) is easily converted to both stearic acid (18:0) and oleic acid (18:1) in the carbohydrate fed state, myristic acid (C14:0) is less easily converted to palmitic acid (C16:0), and lauric acid (C12:0) is only with difficulty converted to myristic acid (C14:0).
The reason for these differences is that, the shorter the chain-length of a saturated fat, the quicker it is converted to energy (oxidised) and thus the less it is available for conversion to a longer fat (elongation).
Dietary carbohydrate inhibits the oxidation of saturated fats and promotes their retention and elongation.
This may explain why people eating low carbohydrate diets are able to eat a larger amount of energy from saturated fat without adverse effects – if indeed there are adverse effects to be experienced by saturated fats. Not only do all the blood markers of “cholesterol” improve (apart from rises in LDL cholesterol in a minority of cases), but the saturated fat content of the blood either decreases or, in a person where it was already low, stays the same.
This is important because most of the health problems associated with saturated fat today are associated, not with saturated fat in the diet, but with a high level of saturated fat in the blood. High levels of palmitate and stearate are linked to insulin resistance, metabolic syndrome, and heart disease.[4,5,6] High levels of myristic acid and palmitate are linked to low levels of HDL and to NASH (non-alcoholic steatohepatitis), the inflammatory liver disease that is a dangerous consequence of NAFLD (non-alcoholic fatty liver disease).[7,8]
High plasma levels of palmitoleic acid (C:16:1 n-9), a rare monounsaturated fat formed when myristic acid is elongated to palmitate, are associated with increased future risk of new-onset type 2 diabetes. This is a good indication that diets high in refined carbohydrate do play a causal role in this pathology, because levels of C16:1 drop once carbohydrate is restricted.
When carbohydrate is restricted, and more fat including saturated fat eaten, the serum level of myristic acid falls more than that of palmitate, probably because its shorter chain-length means that its oxidation was less subject to carbohydrate control to begin with.
It’s also the case that the shorter the chain length of a saturated fat, the more it raises HDL.
And thus a very interesting set of correlations appears:
1: The shorter-chain the saturated fat, the faster it is converted to energy, and the harder it is to elongate.
2: The shorter-chain the saturated fat, the more it increases both HDL and LDL cholesterol at a normal carbohydrate intake.
3: The shorter-chain the saturated fat, the more the serum level in the blood drops when fat replaces carbohydrate
4: As a general rule, when fat replaces carbohydrate, both HDL, and the HDL: total cholesterol ratio, rise.
So, what is the connection? Well, it’s a mystery. So far, none of the references we’ve found actually indicates a mechanism by which some saturated fats raise HDL levels more than others.
We know that dietary fat (both saturated and monounsaturated) replacing carbohydrate increases the transport rate of ApoA-1 in liver cells, and that the decrease in triglyceride-rich VLDL with saturated fat in a low-carbohydrate diet, and the decrease in myristic acid levels, will help retain HDL in circulation long enough to do its job.[11,12]
(Interestingly, alcohol increases the transport rate of both ApoA-1 and ApoA-2, a type of HDL which has “no known function”, but which seems to be beneficial in moderate amounts, but to interfere with ApoA-1 function in larger amounts.)[13,14]
But we don’t yet have a mechanistic, nor an evolutionary, explanation as to why the chain-length of a C12-18 saturated fat and its rate of oxidation should make as much difference as it does to its effect on your HDL level. (Answers on a postcard please).
The bottom line:
– all dietary fats are a mixture of saturated, monounsaturated, and polyunsaturated fats, and monounsaturated fat will make up the largest share of energy in the average low-carb diet (with the exception of coconut-based traditional diets), as it does in your body fat stores.
– It’s possible to eat a diet very high in lauric acid, but only if coconut or coconut oil is a major source of dietary energy. It’s impossible to eat a diet very high in myristic acid. These two fatty acids have the largest impact on HDL levels.
– Eating less carbohydrate will make less saturated fat appear in your blood between meals, even if you do eat more saturated fat, and this is most true for the lauric acid and myristic acid in your diet.
– There will also be benefits in terms of HDL (less) and reduced saturated fat in the blood (more)from a low-carb diet that is higher in monounsaturated fat, and lower in saturated fat than the average, if that’s what you like.
The bottom bottom line: Don’t blame the butter for what the bread did!
*We have some evidence from New Zealand dairy fat expert Joycelyne Benatar that New Zealand dairy fat is, or was, higher in myristic acid than palmitic acid.[15,16] This is consistent with palmitic acid in milk being more the result of carbohydrate feeding (in grain-fed animals), or of animals being fed palm kernel expeller, and myristic acid being more the product of the synthesis of fatty acids from acetate supplied by fermentation.
 DeLany JP, Windhauser MM, Champagne CM, Bray GA. Differential oxidation of individual dietary fatty acids in humans. Am J Clin Nutr. 2000 Oct;72(4):905-11.
 Lossow WJ, Chaikoff IL. Carbohydrate sparing of fatty acid oxidation. I. The relation of fatty acid chain length to the degree of sparing. II. The mechanism by which carbohydrate spares the oxidation of palmitic acid. Arch Biochem Biophys. 1955; 57(1):23-40.
 Volk BM, Kunces LJ, Freidenreich DJ, et al. Effects of Step-Wise Increases in Dietary Carbohydrate on Circulating Saturated Fatty Acids and Palmitoleic Acid in Adults with Metabolic Syndrome. PLoS ONE. 2014;9(11):e113605. doi:10.1371/journal.pone.0113605.
 Sokolova M, Vinge LE, Alfsnes K, et al. Palmitate promotes inflammatory responses and cellular senescence in cardiac fibroblasts. Biochim Biophys Acta. 2017; 1862(2):234-245.
 Lu Z, Li Y, Brinson CW, Kirkwood KL, et al. CD36 is upregulated in mice with periodontitis and metabolic syndrome and involved in macrophage gene upregulation by palmitate. Oral Dis. 2016; Oct 18.
 Eulàlia Montell, Marco Turini, Mario Marotta et al. DAG accumulation from saturated fatty acids desensitizes insulin stimulation of glucose uptake in muscle cells. American Journal of Physiology – Endocrinology and Metabolism. 2001; 280(2): E229-E237.
 Tomita K, Teratani T, Yokoyama H et al. Plasma free myristic acid proportion is a predictor of nonalcoholic steatohepatitis. Dig Dis Sci. 2011 Oct;56(10):3045-52. doi: 10.1007/s10620-011-1712-0. Epub 2011 Apr 23.
 Martínez L, Torres S, Baulies A, et al. Myristic acid potentiates palmitic acid-induced lipotoxicity and steatohepatitis associated with lipodystrophy by sustaining de novo ceramide synthesis. Oncotarget. 2015;6(39):41479-41496.
 Mozaffarian D, Cao H, King IB. Circulating palmitoleic acid and risk of metabolic abnormalities and new-onset diabetes. Am J Clin Nutr 2010;92:1350–8. LINK
. 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
 Brinton EA, Eisenberg S, Breslow JL. A Low-fat Diet Decreases High Density Lipoprotein (HDL) Cholesterol Levels by Decreasing HDL Apolipoprotein Transport Rates. J. Clin. Invest. 1990; 85: 144-151.
 Noto, D et al. Myristic acid is associated to low plasma HDL cholesterol levels in a Mediterranean population and increases HDL catabolism by enhancing HDL particles trapping to cell surface proteoglycans in a liver hepatoma cell model. Atherosclerosis. 2016; 246:50 – 56.
 De Oliveira e Silva ER, Foster D, Harper MMcG, et al. Alcohol Consumption Raises HDL Cholesterol Levels by Increasing the Transport Rate of Apolipoproteins A-I and A-II.
 LW Castellani, Lusis AJ. ApoA-II Versus ApoA-I: Two for One Is Not Always a Good Deal.
 Benatar JR, Stewart RAH. The effects of changing dairy intake on trans and saturated fatty acid levels- results from a randomized controlled study. Nutrition Journal. 2014; 13:32. LINK
 Palmitic acid increased from 15% to 30% of NZ dairy fat, and oleic acid increased from less than 10% to 30%, between 2011 and 2013, matching changes in palm kernel expeller use, at the expense of other saturated fats including myristic acid. Jocelyne Benatar quoted in Listener article by Jonathan Underhill, The Price of Palm Oil, 3 March 2017 LINK
The nutrients that raise and lower HDL and ApoA1.
So is getting your HDL high a good thing? It probably depends if you earned it or not…..and what you eat especially myristic acid
This very interesting study from 2014 brings into focus many of our recent posts about HDL, TG/HDL, ApoB/ApoA1 in the context of our more food-focused posts about butter and the dietary guidelines.
This is a very readable paper which covers a lot of interesting ground.
It looks at the associations between reported intake of micronutrients and macronutrients and a variety of HDL-associated measurements (HDL, HDL-2, HDL-3, and ApoA1) in a case-control cohort (n=1566) selected for a study of coronary artery atherosclerotic disease (CAAD) – the CLEAR study.
The authors are coming off the back of a series of drug trials in which raising HDL had no benefit for CHD outcomes, and also the Mendelian randomisation research showing that genes associated with high HDL aren’t protective, whereas those associated with low LDL are.
The quick bottom line In our opinion this just means that HDL benefit isn’t a gift, but something you might need to work for through diet and exercise – especially keeping your insulin down. A low fasting TG/HDL ratio denotes low-normal insulin levels and the absence of insulin resistance, and that’s why higher HDL is protective against cardiovascular disease (because the higher triglyceride levels associated with insulin resistance on a high carb diet will force HDL down. Interestingly people sometimes get high TG and thus a high TG/HDL ratio when losing weight quickly, but this doesn’t seem to depress HDL).
(our post on the TG/HDL ratio)
The CLEAR study used the Harvard Food Frequency Questionnaire, so the amounts entered weren’t as exact as in feeding studies, but the authors have compared results to feeding studies where available and found the results are very consistent. To allow for inaccuracy of the method, the stronger correlations should be taken as more reliable, as well as more clinically meaningful. The FFQ analysis didn’t measure inessential or non-nutritive phytochemicals, so can’t tell us anything about their effects on HDL.
The strongest positive correlations with all HDL measurements were for myristic acid (C14 – a 14 carbon saturated fat) and alcohol, folate and magnesium were also associated with HDL, EPA (a fish omega 3) with HDL-2, and vitamin C with ApoA1, and fibre with HDL3 (the antioxidant form of HDL that may be most beneficial).
The strongest negative association was with carbohydrate, and there were weak negative associations for iron and animal fat, as well as for arachidonic acid, the long-chain omega 6 found in animal foods, with HDL2.
The latter deserves an explanation – the sample was in a US population and in the US animal fat mainly comes from chicken, with some pork and other processed meats (that are usually associated with carbohydrate, e.g. on pizzas or in hotdogs). Chicken fat has almost no myristic acid or EPA, and is high in AA.
Myristic acid is 16% of coconut oil and palm kernel oil, 7-12% of butter fat, 2-4% of beef and lamb fat, 3% of salmon fat, 2% of lard, and less than 1% of chicken.
Other vegetable oils supply no myristic acid, including the palm oil that’s in junk food.
In a recent Listener article Otago professor Murray Skeaff stated that myristic acid is “far more cholesterol-raising than palmitic acid”. Be that as it may, and we will refrain from asking how much of that cholesterol-raising effect depends on HDL, we note than in every epidemiological study where different types of saturated fat have been measured in isolation, myristic acid has been associated with less harm , or more benefit, than palmitic acid or even stearic acid (which doesn’t raise LDL cholesterol).[3,4,5,6]
This difference is small and statistically insignificant, but it is always consistent, and doesn’t support a view that myristic acid is worse than other saturated fats.
As far as we can see, the main problem with myristic acid is that it can be elongated to palmitic acid by de novo lipogenesis when consumed in a high-carbohydrate diet. The control of C16 and C18 levels by carbohydrate and insulin explains both the higher associations of these fats with disease (or lower protective associations in positive saturated fat studies) and the failure of low fat diets. The rate of oxidation of saturated fats also depends on their chain length, thus C14 will be converted to energy faster than C16 – if fats are being oxidised. This explains why MCT oil (which is mostly C8 and C10 saturated fats) is especially ketogenic. (the rate of oxidation of unsaturated fats, on the other hand, depends on their number of unsaturated bonds; the more they have, the faster they are oxidised and the more ketogenic they are).
If we were designing a diet to raise HDL based on the CLEAR study, the diet would be low in carbohydrate, and its fat would supply myristic acid (not necessarily a very high amount – the CLEAR study subjects were average US dairy fat users) and EPA. Vegetables and fruit would also be encouraged as sources of magnesium, vitamin C, fibre, and folate. Salmon, eggs, and dairy, as foods supplying desirable fats, would replace some of the red meats supplying iron (avoiding processed grains would also reduce the iron content of the diet – note though that the iron correlation, though consistent with other evidence, is not very strong; and that lamb supplies appreciable amounts of EPA).
The animal fat correlation was weak, and the authors didn’t bother to explain it or treat it as meaningful, probably due to a lack of supporting evidence. It is almost certain to be due to confounding from the Harvard FFQ program and the US diet, where animal fats are found together with processed carbohydrate foods. The omega-3/6 balance of animal foods was strongly correlated with HDL2; linoleic acid wasn’t included in the analysis because it correlated too strongly with other dietary fats to be isolated, but ALA (omega-3) was and wasn’t associated with HDL.
Although whole grains are a source of folate, and folic acid is added to most bread today (and to white rice in the USA), iron is also added to refined grains. Legumes supply more folate by weight and per carbohydrate calorie than whole grains, as well as more magnesium and fibre. Organ meats and leafy green vegetables are also good sources of folate.
Interestingly alcohol was dose-dependently correlated with HDL and ApoA1, supported by the cardioprotective associations of moderate drinking. However, there were only a few (21) heavy drinkers (>60g day) in the sample. Because heavy drinking is associated with cancer, accidental death, and heart failure, and is very likely to make you and everybody else miserable in the long run, we don’t recommend this approach to HDL-raising, except for people who already enjoy alcohol in moderation (defined as 10-30g/day, that’s 1 or 2 small glasses of wine or standard drinks).
However, the protective associations between moderate alcohol consumption and CHD clearly show that not every drug that elevates HDL fails to reduce risk. Of course, alcohol is also a food, which might help. Note that, if you do drink, the types of fat that supply most myristic acid in the diet – coconut oil, dairy fat, and beef and lamb dripping – are (along with cocoa butter) those that are most protective against alcoholic liver disease.
Myristic acid raises HDL and LDL cholesterol
Where does the idea that myristic acid is harmful come from? This feeding study showed that myristic acid raised cholesterol, both HDL and LDL – however, to get this amount of myristic acid, 11% of diet, which was supplied by a special 50% myristic acid margarine, from ordinary foods, you would have to eat nothing but butter. Carbohydrate intake in the study was 47% of energy, fat was 39%.
Myristic acid is the third most common saturated fat in the diet. Average intake levels are about 1 g/d in Japan, 6 g/d in the United States, 8 g/d in the Netherlands, and 14 g/d in eastern Finland (D. Kromhout et al, unpublished data, 1988). Major sources are butter fat, which is also rich in palmitic acid, and two vegetable oils, coconut oil and palm kernel oil; the latter two also contain large amounts of lauric acid. Palm oil, another vegetable oil that is high in saturated fatty acids, is low in myristic acid and high in palmitic acid. Palm oil is the number one edible oil worldwide, and its consumption is rising. If much of the cholesterol-raising effect of saturated fatty acids is indeed specifically due to myristic acid, then palm oil would be a suitable substitute for animal fats and hydrogenated vegetable oils in a wide range of products for cholesterol-lowering diets. Moreover, modern biotechnology could be applied to replace myristic acid with palmitic acid in other fats.
The diet, not mentioned in that study, with the most myristic acid – over 20g/day – would have been that of the Tokelau islanders who got most of their energy from coconuts, had a high percentage of myristic acid in adipose tissue (4x that of Europeans) and had very low rates of cardiovascular disease – on a lower carbohydrate diet. 
Carbohydrate controls the HDL response to Myristic acid
What happens to myristic acid on a low carb diet? This study by Jeff Volek et al measured fatty acids in the blood on a 1500 kcal 12% carbohydrate diet (about 50g carbohydrate), compared with a 1500 kcal low fat diet (24% fat, 56% carbohydrate).
(This initial finding was supported by a series of other experiments by this group, including one in which a dose-response effect of carbohydrate on serum C14 levels was demonstrated, and another in which the effect was shown in the absence of calorie restriction or weight loss.)[8,14]
The dietary intake of saturated fat was threefold higher on the CRD (36 g/day) compared to the LFD (12 g/day). Remarkably, the CRD showed consistently greater reductions in the relative proportions of most circulating SFAs in TAG and CE fractions (16), mainly attributed to greater reductions in myristic (14:0; 47% reduction) and palmitic (16:0; 10%) acids. With the exception of those with a low level at baseline, nearly all subjects consuming the CRD had a decrease in total saturates (17 of 20 subjects), whereas only half the subjects consuming the LFD had a decrease in saturates. Taking into account the change in absolute fasting TAG levels, the absolute concentration of total saturates in plasma TAG was reduced by 57% in response to the CRD, compared to 24% in response to the LFD.
Thus we see that, as we would expect, myristic acid in the blood is decreased by carbohydrate restriction faster than longer-chain saturated fats. HDL of course increased in the low-carb arm; which is consistent with this study showing that higher myristic acid in the blood (not diet) of a Mediterranean population is associated with lower HDL. This paper also cites Mensink et al “a large meta-analysis including 60 dietary intervention studies concluded that the increase of HDL-C due to SFA progressively decreases with the elongation of the acyl chain, being maximal for C12:0 (lauric acid) and not relevant for C18:0” – so the faster beta-oxidation of myristic acid (and lauric acid, not isolated in the CLEAR study) correlates with the greater rise in HDL.
And if myristic acid isn’t oxidised, because the carbohydrate content of the diet is too high for the insulin sensitivity of the individual – carbohydrate intolerance – HDL can go down instead.
The following human study also shows that myristic acid modulates omega 3 status;
In addition, in humans, compared with a diet containing 0.6% of myristic acid mainly in the sn-2 position in the TAG [i.e. dairy fat], a diet containing 1.2% of myristic acid during a 5-week consumption period significantly enhanced EPA and DHA levels in the plasma PL and DHA level in the plasma cholesteryl esters . When the intake of myristic acid increased from 1.2 to 1.8% energy in the same population, EPA, DPA and DHA decreased significantly in plasma PL and EPA also decreased in cholesteryl esters . This result suggest that, in humans, the effect of myristic acid on circulating (n-3) PUFA follows a U-shaped curve with a favorable turning point at around 1.2% of total daily energy.
1.2% of dietary energy would be equal to 10-12% of energy from dairy fat. But note that this was in the context of a high carb diet, and that it’s likely this threshold would increase as the rate of myristic acid oxidation increased at lower carbohydrate intakes.
In low-fat diets, it looks like there’s an optimal amount of myristic acid, which you’d get by including full fat dairy foods, as shown by the DASH diet study of Chiu et al (increasing saturated fat from animal foods over baseline improves biomarkers in people eating a supposedly “healthy” diet pattern). The omega-3 study we cited above, and the Med diet serum HDL study, show that in low-fat diets or in carbohydrate intolerant individuals there’s a limit to benefit – a U shaped curve. Putting lots of butter on white bread with jam, or in sweet cakes, as Kiwis did in the 1960’s, you can maybe come off that curve and prang badly. But once you look at lower carb diets, it looks as if myristic acid is a fat that’s well tolerated, doesn’t hang around, and is easy to benefit from (remember, at around 16% of coconut oil, 10% of dairy fat, much lower amounts in other animal fats, and almost none in olive oil and nuts, it’s unlikely to be a major type of fat in the average low carb diet).
The PURE study
And, to turn to the famous PURE study, also a case-control study but a very large one with dietary intakes and lipids stratified into quintiles,
“higher carbohydrates intake has the most adverse effect on lipid profiles and replacing it with saturated fat improved HDL and TG and replacing it with MUFA improved TC/HDL-C and ApoA/ApoB.”
ApoB/ApoA was the lipid marker chosen as the best risk predictor in PURE and the INTERHEART study. Animal fats are predominantly mixtures of saturated fat and MUFA.
We discussed the reasons why using ApoB/ApoA1 predicts that there will be cardiovascular benefits of carbohydrate restriction in this post.
Looking at the evidence around myristic acid shows us, once again, that carbohydrate drives the pathologies fat gets blamed for.
And it shows us, once again, that judging foods based on their effects on cholesterol and LDL as if this was the only game in town has been a huge blunder in terms of public health.
If you erroneously think that replacing fat with carbohydrate, because this will lower cholesterol, is the key to health, and find out this doesn’t work, then restricting certain kinds of fat becomes a logical, but largely ineffective, and sometimes counterproductive, follow-up part of your strategy.
You can even end up thinking that it’s okay that palm oil is overtaking butter in the NZ diet. Not that there’s much evidence that it’s harmful yet, except to orangutans, but surely, it’s just unnecessary, and takes us further away from eating real foods that could be produced at home, and deeper into the hands of a global food industry that hasn’t really looked after our interests so far.
 Kim et al. “Effects of dietary components on high-density lipoprotein measures in a cohort of 1,566 participants.” Nutrition & Metabolism 2014, 11:44.
 Kim DS, Burt AA, Rosenthal EA, et al. HDL‐3 is a Superior Predictor of Carotid Artery Disease in a Case‐Control Cohort of 1725 Participants. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease. 2014;3(3):e000902. doi:10.1161/JAHA.114.000902.
 Zong Geng, Li Yanping, Wanders Anne J, Alssema Marjan, Zock Peter L, Willett Walter C et al. Intake of individual saturated fatty acids and risk of coronary heart disease in US men and women: two prospective longitudinal cohort studies BMJ 2016; 355 :i5796.
 Ericson, U, Hellstrand, S, Brunkwall, L, Schulz, C-A, Sonestedt, E, Wallström, P, et al. Food sources of fat may clarify the inconsistent role of dietary fat intake for incidence of type 2 diabetes. AJCN 2015;114.103010v1
 Praagman J, Beulens JW, Alssema M, et al. The association between dietary saturated fatty acids and ischemic heart disease depends on the type and source of fatty acid in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. Am J Clin Nutr2016;103:356-65.
 Praagman J, de Jonge EA, Kiefte-de Jong JC, Beulens JW, Sluijs I, Schoufour JD, et al. Dietary Saturated Fatty Acids and Coronary Heart Disease Risk in a Dutch Middle-Aged and Elderly Population. Arterioscler Thromb Vasc Biol. 2016; 36(9): 2011-8.
 Lossow WJ, Chaikoff IL. Carbohydrate sparing of fatty acid oxidation. I. The relation of fatty acid chain length to the degree of sparing. II. The mechanism by which carbohydrate spares the oxidation of palmitic acid. Arch Biochem Biophys. 1955; 57(1):23-40.
 Volk BM, Kunces LJ, Freidenreich DJ, et al. Effects of Step-Wise Increases in Dietary Carbohydrate on Circulating Saturated Fatty Acids and Palmitoleic Acid in Adults with Metabolic Syndrome. PLoS ONE. 2014;9(11):e113605. doi:10.1371/journal.pone.0113605.
 DeLany, JP, Windhauser, MW, Champagne, CM, Bray, GA. Differential oxidation of individual dietary fatty acids in humans. Am J Clin Nutr October 2000;72(4): 905-911
 Kirpich IA, Miller ME, Cave MC, Joshi-Barve S, McClain CJ. Alcoholic Liver Disease: Update on the Role of Dietary Fat. Osna N, Kharbanda K, eds. Biomolecules. 2016;6(1):1.
 Zock PL, de Vries JH, Katan MB: Impact of myristic acid versus palmitic
acid on serum lipid and lipoprotein levels in healthy women and men.
Arterioscler Thromb Vasc Biol 1994, 14:567–575.
Prior IA, Davidson F, Salmond CE, Czochanska Z. Cholesterol, coconuts, and diet on Polynesian atolls: a natural experiment: the Pukapuka and Tokelau island studies. Am J Clin Nutr. 1981; (34)8: 1552-1561.
 Volek JS, Phinney SD, Forsythe CE et al. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids. 2009;44(4):297-309. doi: 10.1007/s11745-008-3274-2. Epub 2008 Dec 12.
 Forsythe CE, Phinney SD, Feinman RD et al. Limited effect of dietary saturated fat on plasma saturated fat in the context of a low carbohydrate diet. Lipids. 2010; 45(10):947-62. doi: 10.1007/s11745-010-3467-3. Epub 2010 Sep 7.
 Noto, D et al. Myristic acid is associated to low plasma HDL cholesterol levels in a Mediterranean population and increases HDL catabolism by enhancing HDL particles trapping to cell surface proteoglycans in a liver hepatoma cell model. Atherosclerosis. 2016; 246:50 – 56
 Legrand P, Rioux V. The Complex and Important Cellular and Metabolic Functions of Saturated Fatty Acids. Lipids. 2010;45(10):941-946. doi:10.1007/s11745-010-3444-x.
 Chiu S, Bergeron N, Williams PT, Bray GA, Sutherland B, Krauss RM. Comparison of the DASH (Dietary Approaches to Stop Hypertension) diet and a higher-fat DASH diet on blood pressure and lipids and lipoproteins: a randomized controlled trial. Am J Clin Nutr. 2015. ajcn123281.
 Dehghan M, Anand S, Mente A, Yusuf S on behalf of PURE study working group. OC06_01 Association of Nutrients With Blood Lipids in 19 Countries and 5 Continents: The Pure Study. Global Heart. 2016; (11)2: e6.
If anyone’s interested in the public health nutrition debate around the dietary guidelines, then here’s a summary and critique of our latest jousting round(s) with conventional wisdom.
In late 2016, an article from New Zealand in defense of the current dietary guidelines was published in the renowned medical journal The Lancet. While the authors (who included Prof Jim Mann, Dr Lisa Te Morenga, Prof Rod Jackson, and Prof Boyd Swinburn) ranged far and wide over the justifications for current guidelines, they cited no research critical of them, and ignored the most trenchant criticisms, which allowing them to exaggerate the importance of the evidence that it suited them to address.
An example of their straw man approach is here:
“But the case for reducing carbohydrate in general centres on whether there are benefits associated with reduction of starches and non-starch polysaccharides.”
Non-starch polysaccharides are, in general, what we call fibre. Yet there is no case being made for a weight loss benefit from reducing fibres that we have ever seen (di- and mono-saccharides, or sugars, would be the correct term to include instead). This seems like a rather childish game – “if you’re restricting carbohydrate you must be restricting fibre too, because that’s a carbohydrate”. It also betrays a poor awareness of food composition – a low carbohydrate fruit or vegetable will have more fibre per calorie than a high carbohydrate food.
They claim that dietary guidelines now include a high-fat diet; “a high-fat, high-carbohydrate Mediterranean diet, which is associated with a fairly low risk of many NCDs” but this is about 40% fat. This definition of high fat allows them to make the claim that “Meta-analyses of trials in people not attempting to lose weight show moderately lower bodyweight loss among those on diets fairly low in fat (30% or less total energy) than those on carbohydrate-reduced higher fat diets.”
But in fact not one of the control arms in those studies was “carbohydrate-reduced” in a medical sense, except for the fact that they were a little higher-fat than the interventions, merely representing the normal diets of their day, replete with white flour, partially hydrogenated oils, and sweets. Food quality is an important confounder in diet trials, and in most of the old low-fat and saturated-fat reduced studies the intervention groups were told to eat nuts and fish, whole grains, fruits and veges, and cut back on sugar, flour, and foods made with hydrogenated shortening, making it hard to attribute any benefits to increased carbohydrate or polyunsaturated vegetable oil.
The article re-iterated claims that saturated fat should be replaced with polyunsaturated fat, then stated that pitting one macronutrient against another risks confusing the public.
But what is wrong with telling everyone to eat healthy higher-carb diets?
There are three main problems that we can see:
Firstly, and most importantly, a large, and growing, proportion of the population is carbohydrate-intolerant. They have obesity, metabolic syndrome, excessive TG/HDL ratio, rising HbA1c, if not frank diabetes, and restricting carbohydrate is the most effective way to reverse this cluster of chronic disease associated with hyperinsulinaemia, which is increasing their odds of dying young from heart disease, cancer, diabetic complications and so on. Let us also be clear – carbohydrate intolerant means that these people have difficulty of disposing of dietary carbohydrates without advert metabolic effects of high triglycerides, high blood glucose and hyperinsulinemia.
Secondly, there is no evidence that full-fat dairy is anything but beneficial compared to low-fat (and there’s very little evidence comparing lean and fatty meats). If dairy fat, the most saturated animal fat in existence, doesn’t cause heart disease, then the basis for saturated fat restriction is very weak. There may be benefits from optimal intakes of certain polyunsaturated fats, but there’s no evidence that oils are the best source of these fats, nor that replacing other fats (which will always tend to limit the percentage of fat in the diet) is essential for benefit.
Thirdly, this “virtuous” diet advice might disadvantage the poor. Fat-free milk or (plain) yoghurt is the same price as full-fat milk or yoghurt, yet supplies half as much energy and fewer vitamins. Nuts, fish, and lean meat are more expensive per calorie than cheese, fatty cuts, and eggs. Light coconut cream, cream cheese, or sour cream is the same price as full-fat. If someone makes these low-fat choices, they need more energy from other sources (i.e. are left hungry), but have less money left to ensure its quality. Fruit and vegetables are relatively expensive, and a good whole grain bread costs about four or five times as much as white bread.
We tried to unpick some of these contradictions in a letter to the Lancet, which that journal was gracious enough to publish last week.
Dietary guidelines are not beyond criticism
Mann and colleagues (Aug 27, p 851) claim that criticisms of the dietary guidelines are not evidence-based. However, even by their own account, the promotion of reduced-fat dairy products in existing guidelines is not evidence-based, in view of the lack of association of dairy fat with cardiovascular risk, and the strong protective associations that exist between ruminant fatty acids and type 2 diabetes. This evidence contradicts the theory that the effect of dietary saturated fat on serum cholesterol is the cause of the association between serum cholesterol and cardiovascular disease.
Carbohydrate intolerance is increasing in developed and developing countries, as indicated by growing rates of diabetes, obesity, and metabolic syndrome, with the consequent expansion of health costs. Evidence is emerging that a major nutritional cause of modern chronic disease is the glycaemic environment created by the interaction between insulin resistance and foods with a high glycaemic load (GL), increased consumption of which has been a natural consequence of advice to limit dietary fat.
Mann and colleagues cited two meta-analyses [4,5] excluding weight loss trials, in which low-fat diets were only compared with low quality, high GL control diets. However, in view of the disappointing results in most trials in which a low-fat diet has been compared with alternative dietary interventions, the evidence is unclear on whether a fat-restricted bias in dietary advice is justified. Population dietary guidelines should be adapted to include advice on carbohydrate restriction, which is likely to be beneficial or protective for a large, but growing, proportion of people.
[References are in link]
That’s all. Seems uncontroversial enough right? What we’re saying is that some people do well with low carb advice, and there are today more than enough people in this category to justify including it as an option in dietary guidelines. We’re also saying that the evidence for fat restriction is not so strong that it needs to be a barrier to low carb diets, nor to good nutrition in general.
We weren’t just trolling (or The Lancet wouldn’t have published our letter – The Lancet is harder to get into than the Auckland housing market). We really hoped to be having a discussion about how the low carb idea can be incorporated into guidelines for the people who need it. The UK’s Public Health Coalition showed how this can be done last year, and we started the ball rolling with our own Real Food Guidelines in 2014.
But instead Mann et al. doubled down on their claims.
In particular, they pretended not to understand the idea of carbohydrate intolerance.
We find the link proposed by Henderson and colleagues between “carbohydrate intolerance” and “diabetes, obesity, and metabolic syndrome” puzzling. Carbohydrate intolerance is characterised by abnormal carbohydrate digestion as in lactose intolerance, and is not associated with abnormalities of glucose metabolism.
This from the people who think that carbohydrate restriction means fibre restriction.
Their new justification for low-fat dairy is interesting.
Low-fat, as opposed to full-fat, dairy products are generally recommended to promote consumption of essential nutrients and to allow intakes of food sources of unsaturated fatty acids without promoting excess energy intake.
Basically, we’ve been telling you to eat low-fat dairy so we can feed you extra oil without making you fat. Well guess what people, it’s not working and there is no “totality of evidence” as you always call it for this. In fact, such a body of evidence just doesn’t exist.
This passage makes a point which is not without substance, but deserves further comment:
However, we are unaware of any deleterious effects of minimally processed wholegrains or fibre-rich intact vegetables (notably legumes and pulses) and fruits—which are protective against diabetes, useful in its management, and with additional benefits in terms of cardiovascular and gastrointestinal disease.
On reading this reply, Nina Teicholz, author of The Big Fat Surprise: Why Butter, Meat and Cheese Belong in a Healthy Diet, which is an engrossing and indeed exciting (and deservedly best-selling) history of how the low-fat idea became embedded in official advice despite the continual appearance of evidence to contradict it, wrote a detailed response on PubPeer, which is a post-publication peer-review website.
Iterating a claim made in their initial Comment, the authors again assert that there is a “substantial body of observational, clinical trail, and experimental evidence…[to] support the recommendation to reduce total saturated fatty acids and that they might be replaced with unsaturated vegetable oils.” However, this body of evidence does not exist. There is now a total of at least 17 systematic reviews and meta-analyses looking at the totality of the evidence on saturated fats (1) which have largely concluded that saturated fats have no association with nor any effect on cardiovascular or total mortality.
Furthermore, the authors did not, as they state, summarize the above evidence in their original Comment. Instead, they chose a small selection of the evidence, which they then misrepresented to support their claims about saturated fat. I wrote about this when their Comment was first published (2).
The authors write that this body of evidence “does not negate advice to reduce total saturated fat,” but if a large body of rigorous, government-funded, randomized controlled trials testing saturated fats on more than 50,000 people have found no effect of saturated fats on cardiovascular mortality, then this does indeed negate advice to reduce total saturated fat.
The authors further write that they are “unaware of any deleterious effects of minimally processed whole grains or fibre-rich intact vegetables (notably legumes and pulses) and fruits. If so, then the authors are unaware of the large body of clinical trial research demonstrating that reducing total carbohydrate intake is highly effective for managing or even reversing obesity and diabetes. Thus, for people who are struggling with weight or diabetes, the high-carbohydrate foods listed above might be enjoyed in small amounts, but taken together as a majority of one’s diet, these foods would constitute a high-carbohydrate diet–which has been shown to be entirely ineffective, if not actually detrimental, in fighting these diseases.
That the authors characterize “carbohydrate intolerance” as “lactose intolerance” suggests that they have not read the literature on the effect of glucose and fructose on insulin, fat deposition, fatty liver disease and adverse lipid effects. This large body of literature describes the body’s unique metabolic response to carbohydrates, compared to other macronutrients. It seems uncharitable for the authors to accuse their critics of being engaged in a “continuing attempt to pit one macronutrient against another.” Science is not politics–or at least shouldn’t be. No one is “pitting” macronutrients against each other, like Hillary vs. Trump. Rather, researchers who discuss the observations that the body has a differing metabolic response to different macronutrients are simply following the duty of any scientist: to respond and explain the observations. If their explanation can be countered by a more convincing one, then that’s where a good scientific exchange could take place. Debate over science should be allowed to happen. To accuse researchers who disagree with them of seeking only to “perpetuate confusion,” as the authors write, appears merely to be an attempt to shut down legitimate debate.
Finally, it is untrue that “existing population-based dietary guidelines permit a wide range of macronutrient intake.” In the US, the three suggested “Dietary Patterns” are all modeled at more than 50% carbohydrates (3), which, by any definition, cannot be considered a low-carbohydrate diet.
People who say that carbohydrate restriction means fibre restriction, that carbohydrate intolerance can only mean lactose intolerance, and that 50% carbohydrate diets are the high fat extreme of a wide range of macronutrient intakes, should not accuse others of perpetuating confusion.
I (GH) added a bit of detail below Nina’s PubPeer comment about the circumstances under which fruit and wholegrains appear beneficial for diabetes prevention in epidemiological studies – the amount of carbohydrate from these foods associated with greatest benefit is actually minimal and would fit in most low carb diets.
We wrote another letter in response to Mann et al’s author reply, but as it is unlikely that The Lancet will keep a correspondence going over such a long period, we will post it here.
Dietary Guidelines are already confused.
The position that Mann et al propose be taken towards full-fat dairy foods, to await the results of further research into their benefits, is the opposite of what a public health nutrition approach should be. Nutritious, popular, and traditional foods should never have been advised against until after such research was completed. Advice to use unsaturated oils instead has been based on population studies that did not differentiate adequately between oils and wholefoods as sources of unsaturated fat, except in the case of olive oil, a traditional fat, and the olive oil studies have not shown that the avoidance of full-fat dairy or meat is required for benefit.[1,2]
Semantic quibbles about carbohydrate intolerance are inappropriate – most readers of the Lancet are familiar with the uses of the oral glucose tolerance test, and many will also be familiar with the importance of the fasting TG/HDL ratio, fasting insulin, or two-hour insulin response in predicting the future risk of chronic disease. These are measurements which, if abnormal, will be more sensitive to the ingestion of carbohydrate than of other nutrients.[4, 5] Carbohydrate intolerance is thus a simple formula allowing the public to understand a concept of considerable importance in public health.
Advice to use low-fat or lean versions of traditional foods, in part because of the outdated notion that eating the whole-fat versions of these foods leads to excess energy intake, does not in practice allow a wide range of macronutrient intakes. Instead we propose that it would help to reverse the burden of chronic disease to acknowledge the benefit for some of replacing foods rich in starch or sugar with less carbohydrate-dense whole foods. When conditions such as obesity, type 2 diabetes, and the metabolic syndrome are as widespread as they are today, it is remiss not to include those simple instructions most likely to assist with their reversal in public health diet advice.
 Buckland G, Mayen AL, Agudo A, et al. Olive oil intake and mortality within the Spanish population (EPIC-Spain). Am J Clin Nutr. 2012; 96: 142-149.
 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; 102(6):1563-73. doi: 10.3945/ajcn.115.116046.
 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; Vol. 108(2): 93-99.
 Volek JS, Feinman RD. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction. Nutrition & Metabolism. 2005; 2:31.
 McKenzie MR, Illingworth S. Should a Low Carbohydrate Diet be Recommended for Diabetes Management? Proceedings of the Nutrition Society. 2017; 76 (OCE1), E19
How much evidence do you need to make recommendations about what the public should eat?
It depends really.
“On fair evidence we might take action on what appears to be an occupational hazard. For example, we might change from a probably carcinogenic oil to a non-carcinogenic oil in a limited environment and without too much injustice if we are wrong. But we should need very strong evidence before we made people burn a fuel in their homes that they do not like or stop smoking the cigarettes and eating the fats and sugar that they do like.”
This a quote from a great framework used in public health for making such decisions. It was put forward by Austin Bradford Hill in the 1960s, and has become known as the “Bradford Hill criteria“. It’s a set of conditions that should be met, or tests that should be made, before public health people start to make recommendations about what to avoid and what to do instead.
See also, Austin Bradford Hill, “The Environment and Disease: Association or Causation?”
Proceedings of the Royal Society of Medicine, 58 (1965), 295-300.
So what does this have to do with margarine?
In the previous post, we learned that New Zealanders on average consume around 4.9Kg of butter per capita each year, as well as a similar amount of palm oil, around 8.5Kg of canola oil, and around 2.7Kg of soy bean oil (a total of 21Kg of added fat, similar to the totality of 1966 butter intake). Much of the latter three oils goes into non-dairy spreads (along with smaller amounts of other oils such as corn, olive, rice bran, and sunflower, figures for which were not available). So what do we know about these oils and spreads, and their health effects, and should we be telling people to eat them especially over butter?
What are non-dairy spreads?
Butter is butter; its composition will vary slightly depending on what the animal is fed, so that winter silage produces a paler fat, lower in carotenoids, and the feeding of palm kernel expeller produces a fat in which the beneficial trans, cis fat rumenic acid (or CLA) is partly replaced by other trans fats, the importance of which is still uncertain, but these differences are very small compared to the differences that exist within the categories of margarine and non-dairy spreads. Although we’ll use the terms interchangeably here, food labelled “margarine” (a word few food producers seem to use today), as chemist Laurence Eyres reminded us in the Listener, must by law contain at least 80% fat, whereas spreads are usually lower fat. What Eyres doesn’t tell us is that this can be animal fat – there are budget spreads in the supermarket that contain beef fat as an ingredient. Not that there’s anything wrong with that, but obviously the idea that we can “replace animal fat with non-dairy spreads” is a bit misleading.
It’s curious that no-one who supports the substitution of margarine for butter mentions this, and the reason may be that the substitution exists in their heads as a theoretical one – they don’t actually go down to the supermarket and read the labels on the different products that people are buying and eating, or if they do, they only read the saturated fat information on the label.
A lot is made of the use of partially hydrogenated oils (PHO), a source of trans fats, in margarine, and how these are being removed from the food supply by a voluntary arrangement, with labeling still optional. Other countries have made greater efforts to label and remove industrial trans fats than New Zealand, Australia, and the UK. India introduced mandatory labelling and limits on trans fats from PHO within a short period, and the US FDA withdrew the GRAS (generally recognized as safe) classification from PHO, with a complete ban (barring any exemptions being granted) effective later this year. Note that other sources of saturated fats, and of naturally occurring trans fats, are still GRAS and always will be, so that attempts to combine “trans fat and saturated fats” into some common category of “bad fats” have no validity. But why was PHO included in margarine to begin with?
Butter has a spreadable consistency (at least at the right temperature), partly because its saturated fat content ensures that it is not too runny, and partly because the phospholipids and cholesterol it contains allow the fats to form an emulsion with its small amount of water. The trans fats in PHO were straight chains like saturated fats, so had a similar consistency, while appearing as unsaturated fats when tested in the laboratory (they also, unlike saturated fats, interfered with the conversion of polyunsaturated fats into various signaling molecules, which was a bad thing). So they have had to be replaced with more saturated fats, such as beef fat or palm oil. Lighter spreads that don’t contain these fats need to include emulsifiers and stabilizers; this gives them more in common with other highly processed foods, and also means that you’re paying extra for water. The technology of interesterification means that oils can now be made harder by switching fatty acids around on the glycerol backbone of triglycerides, changing their interactions with one another and thus their consistency, but this technology is only used in some of the spreads on the NZ market.
Vegetable spreads – what evidence is there for benefit?
So is there anything (causally) harmful or good about these products? Do they have health benefits? Bearing in mind the Bradford Hill criteria which look at the scientific evidence. The evidence should be tested against these criteria:
- Strength (effect size): A small association does not mean that there is not a causal effect, though the larger the association, the more likely that it is causal.
- Consistency (reproducibility): Consistent findings observed by different persons in different places with different samples strengthens the likelihood of an effect.
- Specificity: Causation is likely if there is a very specific population at a specific site and disease with no other likely explanation. The more specific an association between a factor and an effect is, the bigger the probability of a causal relationship.
- Temporality: The effect has to occur after the cause (and if there is an expected delay between the cause and expected effect, then the effect must occur after that delay).
- Biological gradient: Greater exposure should generally lead to greater incidence of the effect. However, in some cases, the mere presence of the factor can trigger the effect. In other cases, an inverse proportion is observed: greater exposure leads to lower incidence.
- Plausibility: A plausible mechanism between cause and effect is helpful (but Hill noted that knowledge of the mechanism is limited by current knowledge).
- Coherence: Coherence between epidemiological and laboratory findings increases the likelihood of an effect. However, Hill noted that “… lack of such [laboratory] evidence cannot nullify the epidemiological effect on associations”.
- Experiment: “Occasionally it is possible to appeal to experimental evidence”.
- Analogy: The effect of similar factors may be considered.
Criteria 1 and 2: Strength and consistency of epidemiological evidence
There is a body of epidemiological research that claims that replacing saturated fat (or carbohydrate) with polyunsaturated fat reduces cardiovascular risk. Unfortunately, the association isn’t consistent (there are populations where no association, or the opposite association has been seen, at least from theoretically replacing saturated fat with polyunsaturated fat).[1, 2] However, even in the populations where this association has been seen, there’s no clear evidence that margarine, or cooking oil, is the source of it. The problem is that many minimally refined foods are also good sources of polyunsaturated fat, especially chicken and pork, nuts and seeds, olives and avocadoes, but also meat and dairy; all whole foods add more polyunsaturated fat to the diet than sugar and flour do. There don’t seem to have been many attempts to isolate the polyunsaturated fat in oils and spreads and compare it with that in whole foods and animal fats.
There have only been a few epidemiological studies comparing margarine with butter. In Framingham, which was the original large population followed to test the lipid hypothesis (it didn’t work out – there was never any neat linear association between saturated fat in the diet, LDL cholesterol, and heart disease), using margarine instead of butter was associated with no change in heart disease during the first 10 years, then an increase over the 10 years following. This was attributed to trans fats, but that doesn’t explain the different effects over 10 and 20 years.
“Adjusted for age and energy intake, the risk ratio for CHD for each increment of 1 teaspoon per day of margarine was 0.98 [95% confidence interval (CI) = 0.91-1.05] for the first 10 years of follow-up and 1.10 (95% CI = 1.04-1.17) for follow-up years 11-21. Butter intake did not predict CHD incidence.”
Recently, a study was published claiming a theoretical benefit from margarine use instead of butter for heart attack (MI) risk over a 13 year period.
“Substituting butter or stick margarine with tub margarine was associated with lower risk of MI (HRs = 0.95 and 0.91). Subgroup analyses, which evaluated these substitutions among participants with a single source of spreadable fat, showed stronger associations for MI (HRs = 0.92 and 0.87). Outcomes of total CHD, ischemic stroke, and atherosclerosis-related CVD showed wide confidence intervals but the same trends as the MI results.”
Unfortunately, this study is one we don’t have access to, and the methods are not obvious; however, no number of events is given in the abstract, so it is possible that “theoretical” just means calculated risk from serum lipids. Still, it’s noticeable that even in this study, substituting one type of margarine for another was associated with more benefit than replacing butter.
(Given the variety of non-dairy spreads on the market, and the inconsistency of their ingredients, it might be more helpful if the experts fought over what sort of margarine people should use, rather than whether they should use it instead of butter).
There may be other evidence that using margarine, specifically, is associated with beneficial outcomes, but if so we haven’t been able to find it.
Criteria 4 and 6: Temporality and Biological plausibility
What about oils? There’s an interesting paper from the Nurse’s Health Study that looked at two different sources of the omega 3 fat ALA. A higher consumption of ALA from (soy) oil-and-vinegar salad dressing was associated with a lower risk of fatal heart attacks, RR 0.46 (0.27, 0.76), whereas a higher consumption of mayonnaise was not, RR 0.84 (0.50, 1.44). Yet mayonnaise is the richer food and contributed more ALA to diets than oil-and-vinegar salad dressing (16.7% vs 12.2%). This study didn’t look at intake of margarine as a source of ALA (6.8%). A relevant point is that much of this population was probably deficient in omega-3 fats (American’s don’t eat much fish, and median daily energy-adjusted ALA intake ranged from 0.71 g in the lowest quintile to 1.36 g in the highest quintile), so we are probably looking at the effects of correcting a deficiency of an essential nutrient. Of course, if you’re using lots of oil-and-vinegar dressing, or, to a lesser extent, mayonnaise, you’re also eating a very different type of diet from someone who isn’t.
In this case we have a plausible mechanism, and a suggestion of temporality – correcting a historical deficiency of omega-3 fats in a population with very low intake of them would be expected to improve the blood clotting aspect of fatal heart attacks. Other foods could have supplied the ALA, but soy oil happened to be the source available. The association was only significant when the oil was used in salads, and stronger in women taking vitamin E supplements, but in these cases it satisfied the Bradford Hill criteria for strength, and is broadly consistent with the RCT analysis of Ramsden et al.
This example seems to satisfy all Bradford Hill criteria to some extent, if considered as an correction of a deficiency analogous to the correction of a vitamin deficiency, but much less so if considered as the effect of a substitution for saturated fat (especially considering the body of evidence that a substitution for carbohydrate would be at least as beneficial).
On balance we’d say there isn’t a case as far as Bradford-Hill’s criteria are concerned to say anything about spreads and benefit.
Vegetable oils and spreads – some evidence for harm?
So – is there any evidence that non-dairy spreads and cooking oils have harmful effects? You’ll find plenty of mechanistic arguments and non-human experimental evidence that they do in the literature. But remember Bradford Hill’s criteria – an epidemiological association is convincing when it’s attached to mechanisms, but is also strong (RR approaching 2 or greater is best, though 1.5 is usually accepted), consistent (not contradicted by directly comparable studies), and has a dose-response (more seems worse).
Criteria 3, 5, and 7: specificity, biological gradient, and coherence
Age-related macular degeneration is a common cause of visual impairment and blindness in older people.
A case-control study gave the following results.
Higher vegetable fat consumption was associated with an elevated risk for AMD. After adjusting for age, sex, education, cigarette smoking, and other risk factors, the odds ratio (OR) was 2.22 (95% confidence interval [CI], 1.32-3.74) for persons in the highest vs those in the lowest quintiles of intake (P for trend,.007). The risk for AMD was also significantly elevated for the highest vs lowest quintiles of intake of monounsaturated (OR, 1.71) and polyunsaturated (OR, 1.86) fats (Ps for trend,.03 and.03, respectively). Higher consumption of linoleic acid was also associated with a higher risk for AMD (P for trend,.02). Higher intake of omega-3 fatty acids was associated with a lower risk for AMD among individuals consuming diets low in linoleic acid, an omega-6 fatty acid (P for trend,.05; P for continuous variable,.03). Similarly, higher frequency of fish intake tended to reduce risk for AMD when the diet was low in linoleic acid (P for trend,.05). Conversely, neither omega-3 fatty acids nor fish intake were related to risk for AMD among people with high levels of linoleic acid intake.
This was followed by a prospective study by the same authors looking at AMD progression (important because temporality, the presumed cause preceding the effect, which cannot always be shown in case-control studies, is another of the Bradford-Hill criteria), which confirmed the associations above, but also found that nut consumption was protective. This is interesting, because nuts are a good source of linoleic acid, indicating that linoleic acid in whole foods (where some of it is in phospholipid form) may behave differently from linoleic acid in vegetable oils, where the phospholipids have been removed by refining.
The prospective study found that all fats were associated with AMD – however, there was no dose response in the case of saturated fats. Dose response is an important part of the Bradford Hill criteria – if something is truly harmful, more should (usually) do more harm than a little.
One study, NHANES II, did not find a significant correlation between dietary fats and AMD, however this study failed to separate vegetable oils from other sources of fat, and did not provide a sufficiently detailed breakdown of its results.
This is an example that fulfills many of the Bradford Hill criteria. Indeed it already appears in textbooks as an example of the role of peroxidation in oxidative stress diseases. It has specificity because the retina of the eye is exposed to concentrated UV radiation, and plausibility because linoleic acid and ALA are uniquely prone to peroxidation in vivo. It is known not to be the only factor in AMD, yet shows a strong association, increasing our confidence that it is a factor increasing risk.
One of the predicted harms of higher vegetable oil intake is increased cancer risk, due to the peroxidisabilty of polyunsaturated fats, as well as their use by some types of cancer cells. However, this correlation is not usually a strong or consistent one, because exposure to carcinogens and diet both vary by occupation and socioeconomic class, and because cancer, unlike heart disease, subdivides into many discrete diseases, the risk of which is relatively rare. Further, just agreeing to be in a diet study has a significant effect on reducing future cancer risk. However, there are some exceptions.
The use of vegetable oils for high temperature cooking is fairly consistently associated with lung cancer risk in women using them, for example in this case-control study of women in Gansu, China using rapeseed oil (as far as we can tell, this is the name for canola oil in modern China; at any rate, it comes from the same species and is thought to be healthy) for wok cooking.
A useful feature of this study was that rates of two important confounders, deep fryer cooking and smoking, were very low.
The odds ratio (OR) for lung cancer associated with ever-use of rapeseed oil, alone or in combination with linseed oil, was 1.67 (95% CI 1.0-2.5), compared to use of linseed oil alone. ORs for stir-frying with either linseed or rapeseed oil 15-29, 30 and > or =31 times per month were 1.96, 1.73, and 2.24, respectively (trend, P=0.03), relative to a lower frequency of stir-frying. Lung cancer risks also increased with total number of years cooking (trend, P<0.09). Women exposed to cooking fumes from rapeseed oil appeared to be at increased risk of lung cancer, and there was some evidence that fumes from linseed oil may have also contributed to the risk.
In a Hong Kong case-control study in which deep frying was a common style of cooking, the risk was even higher – indeed, similar to that of smoking. Peanut, corn, and canola were the main oils used (there was little difference between them in this study).
The ORs of lung cancer across increasing levels of cooking dish-years were 1, 1.17, 1.92, 2.26, and 6.15. After adjusting for age and other potential confounding factors, the increasing trend of ORs with increasing exposure categories became clearer, being 1, 1.31, 4.12, 4.68, and 34. The OR of lung cancer was highest for deep-frying (2.56 per 10 dish-years) followed by that of frying (1.47), and stir-frying had the lowest OR (1.12) among the three methods.
The first study is curious because linseed oil, an oil very high in ALA, and one which no-one in the West would use for cooking, seemed safer than rapeseed oil. In the recent Harvard study on dietary fat and mortality, based on Nurse’s Health Study data, ALA was associated with cancer mortality (HR 1.12; 95% CI, 1.04, 1.20). There was both a dose-response and a temporal response (the association was only seen with longer exposure). This association is weak, but lung cancer is only one type of cancer, canola oil only one source of ALA, and ALA rich foods can be used in various ways. The Harvard research analyses foods, rather than the ingredients they are made with, so there’s no information on how much canola oil was being used, but in NZ it seems to be the most common cooking oil. However, the idea that cooking oil fumes cause lung cancer seems to be accepted; yet, here in New Zealand, we’re told to use canola oil in place of animal fats or coconut oil (saturated fat wasn’t associated with cancer mortality in the Harvard study).
This is a case that not only fulfills Bradford Hill criteria for causality (the product of heating the ALA in these oils protects lung cancer cells against apoptosis in vitro), but also fulfills his example of a practical intervention. We could look for less probably carcinogenic oils and fats and introduce (or re-introduce) them into the limited environments of kitchens without too much injustice if we are wrong, provided they are no more harmful once eaten.
Since the removal of PHO trans fats from the food supply, the use of palm oil, the vegetable oil highest in the main saturated fats palmitic and stearic acid, has increased in NZ. Palm oil consumption is equal to that of butter, and most of it goes into non-dairy spreads and other processed foods. The “Myth Buster” section of the Listener article we responded to in the last post failed to mention palm oil use in spreads. Palm oil contains a greater amount of the supposedly “bad” saturated fat palmitic acid than butter, thus defeating the point of using margarine. (However, as the amount of palmitic acid in the blood is controlled by the amount of carbohydrate we eat, and we usually eat much more carbohydrate than palmitic acid, it makes more sense to reduce carbohydrate first, and avoid palm oil, before looking at butter. Coconut oil is very low in palmitic acid). Palm oil production has become a far greater environmental disaster internationally than dairying is said by its worst critics to be for New Zealand. To make matters worse, the European Food Safety Agency recently issued a warning that palm oil contains higher levels of the carcinogen glycidyl, caused by refining at temperatures above 200 degrees C, than those found in other processed oils. New Zealand is still awaiting legislation for the mandatory labelling of palm oil, which often appears on food labels as “vegetable oil”. Remember, the New Zealand population has only been exposed to trans fat, palm oil, and interesterified fat products because locally produced animal fats like butter have been supposed, on inadequate evidence, to be harmful, and because a massive international industry exists to profit by supplying us with artificial substitutes.
So there could be a future increased health risk, as well as the ongoing environmental disaster, caused by our rush to consume palm oil, all in the name of avoiding butter and animal fats. However, there’s no epidemiological study looking at the impact of palm oil in Western countries (nor any for interesterified fats). Bradford Hill can’t help us when studies don’t ask the right questions. Most of the studies we’ve looked at weren’t designed to tell us whether getting our polyunsaturated fats from refined oils instead of real foods was a good idea or a bad one, though we can be pretty sure that they’re not as healthful as they were once heated above 200 degrees C, whether in cooking or refining.
We love the way that Bradford Hill’s thinking does more than just help us decide whether to say yes or no to the question of “does X cause (or prevent) Y?”- it can also lead us into a deeper understanding of what the evidence really means.
The case for benefit from PUFA oils and spreads isn’t met, except for the case for correcting a deficiency of LA or ALA – directly analogous to correcting a vitamin deficiency (analogy). Regarded in this way only, the case for benefit should be clear, but can only apply to oils and spreads in cases where oils are the only source of these fats – this doesn’t have to be the case for ALA, and of course it is not the case for LA in normal diets.
Anyone eating a higher fat, real food diet is likely to have an optimal intake of LA and at least a sufficient intake of ALA or other omega-3 fats without relying on these supplementary sources.
A low-butter spread you can make at home.
Supposing you like the taste of butter, want to avoid potentially harmful refined oils, but are also interested in reducing the amount of saturated fat you eat. Or maybe you want to do your bit to reduce the environmental impact of dairy farming. We suggest adapting a recipe for “Sunbutter” from Gayelord Hausers'”Treasury of Secrets” (1963 edition).
Gayelord Hauser was a diet adviser to the stars in the golden age of Hollywood, who advocated (among other things) low carb diets for weight loss, and the use of what later became known as “health food supplements” such as brewer’s yeast, molasses, and wheat germ oil. His books contain a simple recipe for a low-saturated fat spread, using a pound of butter and a cup of sunflower oil. In our new updated version, you’d heat and blend together equal parts butter and extra virgin olive oil. The result is spreadable straight out of the fridge, and tasty. This might just be the main benefit of the recipe. NZ refrigerators used to have a butter conditioner – a warm section of the fridge, just the right temperature to keep your butter spreadable. These went out with the anti-butter, saturated fat will kill you campaigning of the Heart Foundation and Rod Jackson in the 1990s. Such a loss…
Unlike the original Sunbutter, this mixture will have almost exactly the same fatty acid composition as your own fat stores (credit to Steve Phinney for this insight), and that’s exactly the kind of healthy fat you want to be running on.
And you don’t need to use anything to make it that you wouldn’t normally want in your food.
 Praagman J, de Jonge EA, Kiefte-de Jong JC, Beulens JW, Sluijs I, Schoufour JD, et al. Dietary Saturated Fatty Acids and Coronary Heart Disease Risk in a Dutch Middle-Aged and Elderly Population. Arterioscler Thromb Vasc Biol. 2016; 36(9): 2011-8.
 Praagman J, Beulens JW, Alssema M, et al. The association between dietary saturated fatty acids and ischemic heart disease depends on the type and source of fatty acid in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. Am J Clin Nutr2016;103:356-65.
 Margarine intake and subsequent coronary heart disease in men. Gillman MW, Cupples LA, Gagnon D, Millen BE, Ellison RC, Castelli WP. Epidemiology. 1997 Mar;8(2):144-9.
 Liu Q, Rossouw JE, Roberts MB, Liu S, Johnson KC, Shikany JM, Manson JE, Tinker LF, Eaton CB. Theoretical Effects of Substituting Butter with Margarine on Risk of Cardiovascular Disease. Epidemiology. 2017 Jan;28(1):145-156.
 Hu FB, Stampfer MJ, Manson JE, et al. Dietary intake of α-linolenic acid and risk of fatal ischemic heart disease among women. Am J Clin Nutr. 1999; 69(5): 890-897.
 Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis
 Seddon JM, Rosner B, Sperduto RD, et al. Dietary fat and risk for advanced age-related macular degeneration. Arch Ophthalmol 2001;119:1191–9.
 Seddon JM, Cote J, Rosner B. Progression of age-related macular degeneration: association with dietary fat, transunsaturated fat, nuts, and fish intake. Arch Ophthalmol 2003;121:1728–37.
 Heuberger RA, Mares-Perlman JA, Klein R, et al. Relationship of dietary fat to age-related maculopathy in the Third National Health and Nutrition Examination Survey. Arch Ophthalmol 2001;119:1833–8.
 Metayer C, Wang Z, Kleinerman RA, et al. Cooking oil fumes and risk of lung cancer in women in rural Gansu, China. Lung Cancer. 2002 Feb;35(2):111-7.
 Yu IT, Chiu YL, Au JS, Wong TW, Tang JL. Dose-response relationship between cooking fumes exposures and lung cancer among Chinese nonsmoking women. Cancer Res. 2006 May 1;66(9):4961-7.
 Wang DD, Li Y, Chuive SE, et al. Association of specific dietary fats with total and cause specific mortality. JAMA Intern Med. Published online July 5, 2016.
 Panel on Contaminants in the Food Chain. Risks for human health related to the presence of 3- and 2-monochloropropanediol (MCPD), and their fatty acid esters, and glycidyl fatty acid esters in food. EFSA Journal 2016;14(5):4426 [159 pp.].
Yesterday this headline appeared in Stuff.
Included in the article was a claim from Prof Rod Jackson that
“Butter consumption has increased and the underlying cause of heart disease is a diet high in saturated fat.”
Kiwis follow advice of advocates for high-fat, low-carb diets, who promote foods such as coconut oil and butter, to the detriment of their health, Jackson said.
“Everything was going in the right direction and now people are getting confused. Coconut fat should never go in your mouth, it’s saturated fat.”
We think this is a bit rich. A rise in heart disease was a predictable result of the huge increase in diabetes and obesity in recent years, the very epidemic we’ve been fighting with LCHF advice. The same reversal of mortality trends has happened in America, where LCHF is hardly being blamed. One place it’s not happening is Sweden, which has had mainstream LCHF diet advice and rising butter sales since 2008 – in Sweden heart attack death rates continue to drop steadily, with age-adjusted stats available as recently as 2015.
(In fact the Stuff article states that heart disease rates have already risen in Australia, a country which, as we shall see, is, according to Rod, eating far less butter than us, and where the dietary establishment has been suppressing LCHF advice viciously).
Another good reason why heart disease is rising is that we have an ageing population. The figures in Stuff were not age adjusted, there is a limit to how long life can be extended, and that limit is being reached all around the developed world. People have to die of something; we won’t really know if heart disease is rising until the statistics are age-adjusted – but we suspect it is, because this is an expected effect of a diabesity epidemic that Rod didn’t seem to think was very important with regard to heart disease when we spoke to him last.
How LCHF eating advice – a pattern of eating which reduces almost every cardiovascular risk factor – blood pressure, weight, triglycerides, HDL cholesterol, blood glucose and more – can be blamed for any increases in heart disease mortality is a wonder.
What about Rod’s claim that we’re eating more butter? He expanded on this in a recent edition of the Listener which re-opened the old debate, which is better, butter or margarine (non-dairy spreads)?
The case against butter was presented by Rod and Listener nutrition writer Jennifer Bowden, and the case for margarine was presented by oils and fats chemist Dr Laurence Eyres, so it was a balanced debate.
We don’t agree with their view that butter is bad for you, and causing untold health harms in New Zealand.
Before we go into it, we’re not telling people to eat butter. Olive oil is perfectly good and also has lots of uses. We just don’t see why the average person shouldn’t eat butter, especially in the context of a low carb diet. But we will point out that the category of margarine/non-dairy spread products suffers from multiple issues not addressed in the Listener article, which we’ll get to in a second part of this series.
So are we eating too much butter? First, we need to understand – just how much butter do we eat?
from Index Mundi – the 1986 spike is probably the result of an error that was corrected in 1996.
Professor Rod Jackson, interviewed by Nicky Pelligrino, told us the old historical narrative, that heart disease in NZ started falling as soon as butter intake started dropping from the 1960’s high of 20 Kg annually per capita (385g per week, on average, for every man, woman and child in the country), because saturated fat intakes fell, cholesterol fell, and so on.
The problem with this story is that saturated fat intakes fell slowly, there was a decline in monounsaturated fat too, and most of the replacement energy came from carbohydrates and products with trans fats (margarine became freely available in New Zealand in 1972). Any rise in polyunsaturated fat consumption was small and happened slowly, taking us from about 3% to 5% PUFA by the 1980’s.
There’s no version of the diet-heart hypothesis where a very gradual change of this type would cause a dramatic drop in heart attacks, effective immediately (or even at all, really). We were still eating diets high in saturated fat when heart disease started dropping, and we had been eating them for quite some time, and, per the classic version of the diet-heart hypothesis, coronary atherosclerosis is a slowly progressive disease and its reversal, if it happens at all, requires drastic dietary change.
In Rod Jackson’s version we started replacing butter with olive oil and canola in the late 60’s. No, we didn’t. Oils available in NZ in those days weren’t popular and usually tasted rancid, maybe because they got left in the cupboard for years. People didn’t really start using those products till the 1970’s, which was when the health food movement hit New Zealand. Canola oil wasn’t even invented till the mid-1990’s.
Be that as it may, the most remarkable claim in Rod Jackson’s story is that we are now eating as much butter as we did in the 1960’s. He’s on record from 2014 as saying that NZ per capita butter consumption was up to 11 Kg per annum in 2011, and now he’s saying it’s over 20 Kg and the highest in the world.
That’s right – every man woman and child in New Zealand eats, on average, 400g of butter every week (a block is 500g).
Judge Judy Scheindlin has a book titled “Don’t Pee on my Leg and Tell me it’s Raining”.
This is a case where a little observation on Rod’s part might help to correct a mistaken view. Is it really raining butter?
In the 1997 nutrition survey adult Kiwis (15+) were eating about 7.1% of the 35% of energy that came from dietary fat from butter (about 2.5% of total energy); children ate much less. In the 2008/9 survey, this was halved. Calculating from these figures, unlikely to be very reliable, only gives us around 2Kg a year. Yet even in this year Rod Jackson was quoted as saying “We average around 8kg a year – three times as much as Australians and 16 times more than the Japanese”. So according to Jackson, in 2008, before LCHF and Paleo became popular, the results of the Ministry of Health’s Food and Nutrition Study were completely and utterly wrong, and the average Kiwi was already eating more butter than a butter-friendly low-carber does today, and as much as the average inhabitant of France.
Rod’s data come from the Food and Agriculture Organization (FAO) of the UN, but there are other data available, which come from the dairy industry itself, and the International Dairy Federation has our per capita butter consumption for 2015 at 4.9 Kg, placing us in 7th equal place in world butter consumption.
They should know. But also look around you. My (GH) family of four eats and my (GS) family of five eat butter, and we don’t buy any non-dairy spreads. The two adults, but not the teenagers, eat LCHF (both GS and GH). We buy one 500g block most weeks (some weeks we don’t need to replace it). We use a little ghee too (GH). Together this adds up to about 550g butter fat; that’s 7.2 Kg per year per capita. But we’re exceptional families (maybe?), because someone is still buying the margarine and non-dairy spreads, someone is still cooking with soy and corn oil, and someone is still using vegetable shortening in their baking. Canola oil consumption in NZ is almost double that of butter, according to the industry data. These things haven’t gone away – and most of them didn’t exist in the 1960’s, when butter was the main fat in recipe books, and the only spread in the shops. We sometimes see butter in other people’s shopping trolleys, but more often see the cheaper oils and spreads. New Zealanders don’t eat more fat today than we did in the 60’s, so how do we fit all these oils and spreads in if we’re now eating the same amount of butter we ate back then?
Another factor is that Kiwis eat out more often and eat more processed and fast food than we did in the 1960’s. Takeaway food and processed food are hardly ever made with butter, and even restaurant food doesn’t supply much. The 1960’s equivalent of processed food was Edmonds’ Cookbook recipes made with equal quantities of butter, sugar and flour, or white bread with butter and jam, cheese, or luncheon meat (and if there were any adverse health effects of butter in the 1960’s NZ diet, you don’t need to look any further than those combinations, which accounted for most of the butter eaten).
So it looks to us that the IDF estimate of around 5 Kg per annum has to be much closer to the truth than the FAO estimate of 20 Kg, even if, as we expect, butter consumption per capita is increasing.
Why does this matter?
It’s important that public health advice be based on statistics that are as accurate as possible. Rod Jackson is fairly representative of the anti-saturated fat approach in New Zealand public health. In 2008 he called for a tax on butter (“professor calls for tax on poison butter“).
His colleagues present proposals modelling the effects of saturated fat taxes in New Zealand. If Jackson and his colleagues are basing their thinking on the FAO estimate, and it is badly wrong, as we think it may well be, then these models, such as they are, will be inaccurate. Further, if a scare story is published claiming we eat too much butter, and this is why we’re having heart attacks (sure, it has nothing to do with low-fat sugary treats and KFC cooked in canola oil), and the estimate of how much butter is being eaten in that story is out by a factor of 3 or 4, then the claim is based on an alternative fact.
Plainly, we need much more reliable data than we currently have to make any claims about butter consumption in NZ today.
As for the claim that coconut oil is somehow responsible – coconut oil is expensive. It’s not a big seller in supermarkets. It’s being bought by health conscious people and used as part of a diet that’s overall lowering their risk. It’s very unlikely to have come anywhere near the rise in heart attacks; we note that both the Stuff article and a recent Listener article focus on the stories of younger people who had heart attacks with no warning, because their cholesterol was low. So that hardly tells us that butter or coconut oil are dangerous – it tells us, rather, that Rod Jackson’s preferred risk marker is dangerously unreliable.
To make public health recommendations about a food like coconut oil is a step way past any criterion that should be used by public health practitioners. More specifically the criteria set out by Bradford Hill are simply not met. Its time to get sensible about public health recommendations around saturated fat and coconut oil.
For metabolic syndrome, maybe it’s time to look at other results, like the fasting TG/HDL ratio and HbA1c, and to start taking the epidemic of diabetes, obesity, and the metabolic syndrome more seriously, seriously enough to start applying effective measures like LCHF more widely.
Addendum: some more realistic data on the butter increase
Here’s some figures that seem to fit the facts. They come from the US Department of Agriculture’s yearly reports and are based on industry monitoring.
– From 2009 -2011, NZ butter consumption was at its lowest ever – 20 thousand metric tonnes. In 2012, about the time we (GS and GH) started to eat LCHF, Pete Evans went Paleo, and so on, it went up 5%, and went up another 4.7% in 2013. Consumption has stayed stable since then, on 22 thousand metric tonnes.
So a 10% increase over the lowest-ever consumption rate can possibly be attributed to LCHF, Paleo, and the Real Food movement, etc (and to New Zealand’s ever-growing population).
However, in 2013, rapeseed oil (canola) increased 5.71% and in the following year 2.70%
Palm oil consumption also increased by 36% in this period, and is now equal to butter consumption.
Soybean oil, the other main oil in spreads and other processed foods, fluctuated a fair bit but overall stayed stable during this period.
Canola and palm oil together – oils and spreads – accounted for a bigger increase in saturated fat intake in NZ than butter during the period in question, proving that Kiwis in general didn’t turn away from these foods at all.
In part 2 of this series we’ll look at What, if Anything, is Wrong with Margarine?
 Jody C. Miller, Claire Smith, Sheila M. Williams, Jim I. Mann, Rachel C. Brown, Winsome R. Parnell, C. Murray Skeaff. Trends in serum total cholesterol and dietary fat intakes in New Zealand between 1989 and 2009. Aust NZ J Public Health. 2016; Online; doi: 10.1111/1753-6405.12504.
By George Henderson and Grant Schofield
If you have a standard lipid test done in New Zealand and most other parts of the world, it will usually give a couple of ratios at the bottom. One of these is the fasting triglyceride-to-HDL cholesterol ratio.
It can also be calculated from the other measurements using this online calculator.*
Note that the reference range says that under 2 is ideal, 2-4 is “normal”, over 4 is high.
In our opinion TG/HDL ratios in the 2-4 range may be normal, but they are still likely to be unhealthy or predictive of future ill health. Why is this?
Fasting triglycerides (TG) are usually low (<1) in low carb, fat-adapted people. An exception can be during rapid weight loss.
If TG are high in the fasting state this indicates insulin resistance, and when triglycerides are too high their transfer to the HDL particles causes the HDL count to drop. Because the natural range of TG is fairly wide and context-dependent, the value of this single measurement is disputed, and HDL and the fasting TG/HDL ratio are taken as the more sensitive markers.
Another value is that these are cheap markers which are commonly tested. While there others that may be better, such as fasting insulin or 2-hour insulin, the TG/HDL ratio, especially considered in the context of other common measures including HbA1c and LDL cholesterol, often gives a valuable “look under the hood” at the state of metabolism and hormonal health.
We are constantly asked to comment on standard lipid panels. We think the TG/HDL ratio tells you a fair bit. So here’s our take.
First we will discuss evidence for HDL independently, then for the TG/HDL ratio.
This slide is from the SMART study group, and represents the risk for “all vascular events” in a lipid-lowering trial in 6,111 individuals with a previously diagnosed arterial disease. The controls were a group taking a low-dose statin that didn’t significantly lower their LDL. As you can see, only the control arm in the highest quartile for HDL at baseline had a significant risk reduction. The mean baseline TG/HDL ratios by HDL quartile were 6.2, 3.6, 2.9, and 1.6.
What’s intriguing about this is that these are people with pre-existing arterial disease, often from years earlier (historical). The high HDL quartile has the lowest rates of diabetes and metabolic syndrome and the lowest BMI (25.1 vs 28.1) and waist circumference (92 vs 99.3 cm), so does this group include more historical cases, and represent to a greater extent these men and women who, after their event or diagnosis, managed to improve their hormonal metabolism in various ways? We don’t know, because this kind of evidence isn’t supplied, but an earlier study from the SMART study group showed this interesting correlation between HDL , LDL and new events in a population at high risk (with high cholesterol or high blood sugar). Highest HDL (≥1.50 mmol/l) is protective in people with high LDL (≥2.5 mmol/l), whereas for those with low LDL, a lower HDL is sufficient (≥1.26). Again this is with a TG/HDL ratio of 1.6 in the combined upper HDL quintile, and 2.7 in the 4th quintile.
Some further evidence about TG and HDL comes from an older set of data, the Helsinki Heart Study. In this study a fibrate, Gemfibrozil, was used to lower cholesterol (fibrates lower triglycerides and small, dense LDL), and there was an untreated placebo arm (black bars). Here in this placebo arm we can clearly see the effect of triglycerides and HDL in reducing risk.
In the placebo group (n = 2,045), the low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio was the best single predictor of cardiac events. This ratio in combination with the serum triglyceride level revealed a high-risk subgroup: subjects with LDL-C/HDL-C ratio greater than 5 and triglycerides greater than 2.3 mmol/l had a RR of 3.8 (95% CI, 2.2-6.6) compared with those with LDL-C/HDL-C ratio less than or equal to 5 and triglyceride concentration less than or equal to 2.3 mmol/l. In subjects with triglyceride concentration greater than 2.3 mmol/l and LDL-C/HDL-C ratio less than or equal to 5, RR was close to unity (1.1), whereas in those with triglyceride level less than or equal to 2.3 mmol/l and LDL-C/HDL-C ratio greater than 5, RR was 1.2. The high-risk group with LDL-C/HDL-C ratio greater than 5 and triglyceride level greater than 2.3 mmol/l profited most from treatment with gemfibrozil, with a 71% lower incidence of coronary heart disease events than the corresponding placebo subgroup. In all other subgroups, the reduction in CHD incidence was substantially smaller.
Summary so far: From both the SMART study and Helsinki we see that the TG/HDL ratio is especially important when LDL cholesterol is high. Why is this?
In this graph from a paper by Boizel et al you see that the TG/HDL ratio predicts LDL particle size. The proportion of small, dense atherogenic LDL particles rises sharply, and the proportion of intermediate and large particles falls, as the TG/HDL ratio increases in these patients (n=60 with type 2 diabetes and HDL ≥ 1 mmol/l).
The typical dyslipoproteinemia of type 2 diabetes is characterized by elevated VLDL, small (dense) LDL particles, and decreased HDL (4). The percentage of individuals having small LDL is increased by at least twofold in type 2 diabetes (5).
The prevalence of this qualitative abnormality of LDL has been reported to be surprisingly high, even in the absence of the characteristic diabetic dyslipidemia. Thus, up to 45% of patients with low triglyceride (TG) levels and an even higher percentage of patients with borderline hypertriglyceridemia have small LDL, in comparison with 30% in nondiabetic men and 10% in nondiabetic women (5–8).
Three prospective studies have established that small dense LDL is the best predictor
of future coronary artery disease (CAD) in nondiabetic subjects, even after adjustment for confounding by TG, LDL cholesterol, and HDL cholesterol levels (9).
These authors propose a TG/HDL ratio cut-off of 1.5 to diagnose atherogenic LDL particle size in people with type 2 diabetes.
The fasting TG/HDL ratio is highly correlated with 2-hour insulin (insulin levels 2 hours after consuming glucose) and, with a higher cut off, is also predictive of fasting hyperinsulinaemia. Insulin activates the same HMG-CoA reductase (HMGR) pathway that statins inhibit.[6, 7, 8] This explains why the protective effects of HDL and of statins are not at all additive, and why in SMART and Helsinki, as well as the JUPITER trial, lipid lowering treatments made little or no difference to high HDL and/or low TG groups, who were already at lower risk.
This evidence also predicts that drugs such as statins may be more effective than the large studies say they are when patients are carefully chosen on the basis of individual diagnostic markers, including the fasting TG/HDL ratio; bearing in mind, however, that this is an easy marker to change with a low carb healthy fat diet, which, if it changes the TG/HDL ratio, will also change LDL particle size and insulin levels for the better, amongst other things. There will be less chance of harmful side effects on the LCHF diet compared to drug interventions.
- LCHF will have an important and postive effect on the fasting TG/HDL ratio
- Fasting is critical. There has been a tendency in NZ, to go with non-fasted. We imagine this is just easier because of compliance issues. But it totally ruins the ratio as TG change rapidly when you eat. They are very prone to a rapid rise with carb intake because insulin fluxes carb-derived TG out of the liver.
- Fasted TG and HDL measures will mean your estimate of LDL (which is never directly measured) will be more accurate. So our advice is to do the blood lipid tests fasted for a more accurate and meaningful result.
Lowering of 2-hour post-prandial insulin response by a 20% carbohydrate diet vs 40% carbohydrate, from Gannon and Nuttall 2009.
*Note that the TG/HDL ratio in NZ is calculated using mg/dl values, as in the US, even though NZ lipid measurements themselves are given in mmol/L. mmol/L ratios, which give different numbers, are used in Europe, but all the literature we’re citing here is using the mg/dl ratios, which are in any case more convenient.
 van de Woestijne AP, van der Graaf Y, Liem A, Cramer MM, Westerink J, Visseren FJ. Low High-Density Lipoprotein Cholesterol Is Not a Risk Factor for Recurrent Vascular Events in Patients With Vascular Disease on Intensive Lipid-Lowering Medication. J Am Coll Cardiol.2013;62(20):1834-1841.
 Hajer GR, van der Graaf Y, Bots ML, Algra A, Visseren FL; SMART Study Group.
Low plasma HDL-c, a vascular risk factor in high risk patients independent of LDL-c.
Eur J Clin Invest. 2009 Aug;39(8):680-8. doi: 10.1111/j.1365-2362.2009.02155.x. Epub 2009 May 12.
 Manninen V, Tenkanen L, Koskinen P, et al.
Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment.
 Boizel R, Benhamou PY, Lardy B, Laporte F, Foulon T, Halimi S. Ratio of triglycerides to HDL cholesterol is an indicator of LDL particle size in patients with type 2 diabetes and normal HDL cholesterol levels. Diabetes Care. 2000 Nov;23(11):1679-85.
 Li C, Ford ES, Meng YX, Mokdad AH, Reaven GM.Does the association of the triglyceride to high-density lipoprotein cholesterol ratio with fasting serum insulin differ by race/ethnicity?
Cardiovasc Diabetol. 2008;28;7:4.
 Ness GC, Zhao Z, Wiggins L.
Insulin and glucagon modulate hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity by affecting immunoreactive protein levels.
J Biol Chem. 1994 Nov 18;269(46):29168-72.
 Vincent TS, Wülfert E, Merler E.
Inhibition of growth factor signaling pathways by lovastatin. Biochem Biophys Res Commun. 1991 Nov 14;180(3):1284-9.
 Chen H, Ikeda U, Shimpo M, Shimada K.
Direct effects of statins on cells primarily involved in atherosclerosis.
Hypertens Res. 2000 Mar;23(2):187-92.
 Gannon MC, Nuttall FQ.
Control of blood glucose in type 2 diabetes without weight loss by modification of diet composition.
Nutrition & Metabolism2006;3:16
I’ve witten a lot about fuelling for training and racing for sport performance, especially endurance, and most especially Ironman triathlon. That’s what inspired What the Fat? Sport Performance, and several blogs about this guy: Bevan McKinnon and his sucess in using low carb healthy fat.
He’s now the current Ironman 70.3 and Ironman Hawaii World champion. That follows from his record time for an age grouper at Ironman NZ, Match 2016, and an group win in the ITU long course world champs in 2015.
Here’s the audio of my interview with Bevan following all this success and just exploring the in’s and out’s of nutrition in training and racing at the highest level.
Its a good listen with lots of gems from a very experienced athlete ad coach. Total time 34 minutes.
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.