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.
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