Flow mediated dilation (FMD) is one of the last bastions of low fat dogma. FMD is particularly interesting as you appear to be able to prove almost anything with it. I suspect that results in general are very dependent on exactly how you set up a given experiment and how you report the numbers but most of the papers I've read take the background physiology as given and just supply you with the percentage change. Frequently FMD is enhanced under low fat weight loss conditions and obtunded under low carbohydrate weight loss or even after a single high fat meal.
Let's take a fairly typical study such as this one:
Benefit of Low-Fat Over Low-Carbohydrate Diet on Endothelial Health in Obesity
It uses the term "Atkins" and was published in 2008, a time when ketogenic dieting was less acceptable than nowadays. It's nice because the food intake was tightly controlled and the low carbohydrate group was in ketosis throughout. And it also gives me lots of numbers to play with from the results section.
Table 2 of the results is the most interesting. From the bottom line we can see that there is nothing wrong with the ability of the brachial artery to dilate, if you supply nitroglycerin as a nitric oxide source then there is no difference between groups at any time point for the ability of the artery to respond. What changes is the willingness (or ability/need) of the endothelium to generate the nitric oxide in situ to dilate the artery as flow increases in the low carbohydrate group compared to the low fat group. This shows in line three.
Nothing throughout Table 2 is statistically significant except for line three, that ability of the brachial artery to dilate after occlusion. It's a ratio of before and after occlusion, expressed as a percentage. This went down a little after six weeks ketogenic eating and up a little under low fat eating, giving p as less than 0.05, which means ketogenic eating is Bad For You. That's where the paper stopped. I carried on because the numbers making up the ratio are provided and they are interesting.
So next place to look is line two. This is the maximum diameter of the artery after occlusion is released. There is basically no difference in this parameter with time in either group. A little up and down but basically static.
Then there is line one. Line one shows the basal diameter of the artery in the LC group increasing linearly from 3.42mm to 3.58mm over time. The LF group does an up and a down, ending up dropping from 3.94mm to 3.85mm over the study.
[Addendum, see final conclusions: Does the upping and downing of the LF group reflect changes in FFA release with weight loss, high at 2 weeks and low at 6 weeks as the weight loss bottoms out for the LF group? We don't have enough numbers for weight change or FFA levels to check this, but it fits my ideas]
It is the behaviour of the resting diameter which differs between the groups on a background of a fairly static peak diameter. ie the peak diameter doesn't change much but LC/ketogenic eating progressively increases the basal diameter of the brachial artery. The artery doesn't need to dilate as much after 6 weeks of ketogenic eating to get to the maximal diameter needed to supply the post-occlusion hyperaemia of the forearm.
Conclusion: LC arteries are dilated at rest, they don't need to dilate much more to reach the "normal" size of a post occlusion hyperaemia distended artery.
You could leave it at that.
But I can't.
We have a set of diameters and a set of measured blood velocities. So I can crudely estimate the blood flow, aka the oxygen delivery. That's πr2 times the mean speed of the blood, not forgetting to convert the cm/s velocity to mm/s.
Under basal conditions the blood flow increases for the LC group over the six weeks, from 3326mm3/s to 3876mm3/s, up by 17%.
Basal blood flow for the low fat group decreased from 3939mm3/s to 3668mm3/s over the same period, that's down by 7%.
I have no idea whether these changes are statistically significant but they might well be clinically significant. If I had occlusive peripheral vascular disease I know what I would eat. But you knew I'd say that anyway!
Post occlusion hyperaemic blood flow for the LC group started at 6542mm3/s and increased to 7760mm3/s by six weeks, up by 19%.
For the low fat group the start was 8587mm3/s and this increased to 8752mm3/s, up by, err, 2%.
The gain for ketogenic eating, in peak hyperaemic blood flow, is ten times that of the low fat group. Both ended up about the same, but the LC group had a lower initial value. What would have happend on a level playing field at entry point? That we'll never know because it's probably set by the physical size of the forearms of the subjects...
Conclusion: As a percentage of entry point, the maximal post occlusion flow for LC shows a much greater increase over the six weeks of the study.
I could leave it at that.
But I can't.
Oxidising fat produces roughly 5% more ATP per unit oxygen consumed compared to oxidising glucose. Ketones work some magic on the redox spans of the ETC and on the energy yield of ATP hydrolysis. The ketogenic dieters were genuinely positive for urinary acetoacetate every day. So they actually need less oxygen, yet they had a greater oxygen supply to their forearm... Of course, we don't know the mixed venous oxygen tension but we've all read D'Agostino's rats and know it's probably high under ketones, if the arterial oxygen tension is anything to go by.
It's pretty obvious that these ketogenic folks were uncoupling. They ate 100kcal more per day for 6 weeks than the LF group and lost more weight, more fat and less lean mass. Hard to believe I know, but I tend to believe the results in this paper because the numbers trash low fat eating again and again, while the authors are clearly lipophobes.
Uncoupling may be wasteful of oxygen but is advantageous for protecting our mitochondria, plus the excessive use of oxygen is offset by the oxygen sparing effect of ketones. With the onset of limited oxygen availability the ATP levels will drop and so uncoupling will stop, while ketones will continue to be oxygen sparing. Ketosis is a pretty good state to survive an occlusive episode.
No wonder ketogenic eating limits the need for vasodilation after brachial artery occlusion...
Conclusion: Ketogenic eating is the Bee's Knees for surviving ischaemic episodes.
That's pretty well it for this post. I'm about to stop, except to speculate as to why limited FMD is a good predictor of poor cardiovascular health.
Fat. Low FMD is a marker of using fat as a major metabolic fuel. Under fat oxidation your brachial artery will already be dilated so it won't dilate much more after an occlusion episode. If you are eating a diet of total crap based on carbohydrate it is quite possible to have elevated FFAs combined with elevated blood glucose, once your adipocytes have been stuffed so full that they won't take any more and leak FFAs despite elevated glucose and insulin. Innapropriately elevated FFAs is the disaster recipe, a hallmark of metabolic syndrome.
Elevated free fatty acids (and their oxidation) is Bad For You under metabolic syndrome but it is completely normal under ketogenic eating.
My overall conclusion: Reduced FMD is an epiphenomenon cause by fat oxidation. Fine when it's appropriate. Bad if you are overweight, insulin resistant and eating sugar.