Failure of LC/HF Diets to Suppress NEFA Release

Thanks to reader MM, I have procured a full text copy of the following study that I've discussed a bit previously:  Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet

A bullet pointed, sometimes paraphrased abstract/summary:

  • This study compared a low carb (less than 20g/day, no fat content provided but "high fat") diet to a high carb diet (55% energy, 30% fat) 
  • Fasting, 24 hour AUC (cumulative exposure) and time courses for metabolites were measured during weight loss.
  • Subjects were healthy, obese adults (n = 32; 22 women, 10 men) - diabetics and those with a history of CVD were excluded.
  • The study lasted six weeks. 
  • A 24-h in-patient feeding study was performed at baseline and after 6 wk. Glucose, insulin, free fatty acids (FFAs), and triglycerides were measured hourly during meals, at regimented times. Remnant lipoprotein cholesterol was measured every 4 h.
  • Results:
  • Patients lost a similar amount of weight in both groups 
  • There was no difference between groups on fasting triglycerides or on remnant lipoprotein cholesterol, which was the main outcome. 
  • Fasting insulin decreased, and both fasting and 24-h FFAs  increased within the High Fat group. 
  • Twenty-four-hour insulin decreased for both groups. 
  • Fasting LDL cholesterol decreased in the High Carb group only.
  • In both groups, the differences in fasting and 24-h FFAs at 6 wk were significantly correlated with the change in LDL cholesterol.
  • Conclusions: Weight loss was similar between diets, but only the high-fat diet increased LDL-cholesterol concentrations. This effect was related to the lack of suppression of both fasting and 24-h FFAs.

I was asked a little while back if NEFA levels would correlate with triglyceride levels since the liver packages up excess fatty acids.  Under normal metabolic conditions, this should be the case.  Hyperinsulinemic insulin resistant folks have high NEFA and triglyceride levels.  But we know that low carb dieting is infamous for reducing triglyceride levels, but we also know that, even with weight loss, low carbing can significantly raise LDL in some, if not many, low carbers.  The results of this study would seem to indicate that, if this is the case for you, if you have high LDL, you also probably have elevated NEFA.

OK, so in the above study, they compared various variables for the 2 groups under baseline & diet treated states.  Therefore the subjects' baseline measurements served as their own control group, "before" if you will.  It's a bit confusing, but the baseline measurements seem to have been taken after all participants ate a "regular diet" 55% carb/30% fat/15% protein at estimated weight-maintenance levels individualized to each participant.  Each 24 hour monitoring began at 8am with blood drawn just before their first meal after a 12-hour overnight fast.   The arrows indicate the meals.  The results for insulin and free fatty acid concentrations are shown below: (as always, click to enlarge)

Unfortunately they don't give us glucose levels but we notice that the "insulin spikes" for the baseline "high carb diet" subside, and all 3 groups returned to fasting levels by 5 hours post dinner and relatively close within 3-4 hrs, and stayed there for the remaining 9 hours of the study.  So insulin spikes did not lead to hyperinsulinemia.  Predictably insulin did "spike" with the high carb diet, but the spikes were lower for the calorie-reduced weight loss diet.

Now, look at the FFA's.  The HC weight loss diet curve mostly follows that of baseline weight-maintaining HC diet.   It's predictably a bit higher with weight loss because fat is being mobilized from stores. But now look at the LC group.  Fasting levels are significantly DOUBLE baseline for the LC group.  Granted they are close to double in the HC-weight loss group (see, you do "lose weight while you sleep ;-)  ... ), but they do not stay there long during the day.   Rather they plummet postprandially as insulin properly suppresses their release.  The LC group?  NEFA remains elevated pretty steadily the entire day.  THAT, my friends, is CHRONIC elevated NEFA.  The lowest level they reach is around 600 vs. about 400 baseline for the weight-maintaining diet (that's a 50% elevation above normal, and considered an "abnormally high" NEFA level).  

Given that both groups lost equal weight, and if anything the water weight portion is higher initially with low carbing, it is reasonable to assume both groups of dieters "cleared" equal amounts of stored fatty acids from their bodies (if not more on HC v. LC).  

This SHOULD be alarming, IMO.  

I'm efforting finding a chronicling of 24 hour NEFA/FFA levels during fasting but I would be surprised they would be anywhere near these levels.  Also efforting this for diabetics.  When I find these I'll post a "part II" to this.