Thursday, June 07, 2007

Back to Our Regularly Scheduled Program

You may recall the alarming headlines reported here that suggested a high-fat meal was very risky to endothelial function; one went so far as to suggest just one bite of a burger might kill you!

Seems some researchers thought maybe it's a good idea to see what effect a high-protein (low-carb) and low-fat (high-carb) habitual diet might have on endothelial function over a longer period of time - say, maybe a year?

Wonder why you haven't seen any headlines on the latest study - Effects of weight loss on a low-carbohydrate diet on flow-mediated dilatation, adhesion molecules and adiponectin - published in the British Journal of Nutrition?

Might be because the researchers found nothing significantly different between the two diets, and noted "weight loss does not improve FMD [flow mediated dialation]."

Paper gets published, media sees it, notes noting to see here, no sexy headlines....not quite juicy enough to waste readers time with (even though it contradicts those one-meal experiements), so let's just move on.

But wait!

Just because the study objective was to see effect (benefit or risk) on FMD, adhesion molecules and adiponectin, was there anything else they measured that did have significance and is worthy of our time to look at?

How about we take a look?

Two groups of subjects were randomized into two different dietary protocols - the first included 13 people assigned a low-carbohydrate diet (40% protein, 27% carbohydrate and 33% fat; 26g fiber daily); the second included 12 people assigned the high-carb diet (20% protein, 60% carbohydrate, 20% fat; 40g fiber daily).

Both groups were weighed, measured, poked and prodded and followed up with a 6-weeks, 12-weeks and 52-weeks. Measurements and testing included weight, BMI, blood pressure, cholesterol, glucose, insulin, CRP, VCAM1, sICAM1, E-selectin, P-selectin, and total adiponectin. In addition, vascular measurements were taken for blood pressure analysis and endothelium-dependent FMD, along with an assortment of other tests.

The various measurements were duly recorded for baseline and re-measured during follow-ups, and were included in the final paper. Some critically important measures were statistically significant, but not the focus of the study design; thus not highlighted in the abstract conclusions.

We hear a lot about how low-carb diets are bad for cholesterol.

In this study, like others, total cholesterol, LDL and triglycerides were lowered over the course of the year and HDL rose while following the low-carb diet.

Total Cholesterol:
Baseline = 5.3
52-weeks = 4.62
[low-fat group went from 5.7 to 4.94]

Baseline = 3.5
52-weeks = 2.69
[low-fat group went from 3.8 to 3.07]

Baseline = 1.3
52-weeks = 1.44
[low-fat group went from 1.3 to 1.34]

Baseline = 1.7
52-weeks = 1.07
[low-fat group went from 1.4 to 1.34]

Intriguing too was the improvements with glucose and insulin following the low-carb diet:

Glucose (fasting):
Baseline = 5.9
52-weeks = 5.19
[low-fat group went from 5.8 to 5.5]

Insulin (fasting):
Baseline = 16.9
52-weeks = 7.28
[low-fat group went from 12.1 to 5.22]

An interesting finding was that adiponectin, a hormone involved in a number of metabolic processes, including glucose regulation and fatty acid catabolism, "did not change significantly after 12 weeks of weight loss" (p=0.10), but increased (good) at the last measurement, 52-weeks, at the end of the study (p=0.05).

Blood pressure (not high at baseline) improved, from 122/75 at baseline to 115/68 at the 52-week measure; for those on the low-fat diet, blood pressure increased from 122/75 at baseline to 130/74 at 52-weeks.

It's clear in the data that both dietary approaches offered improvements with weight loss in the above measures of risk factors. Something though wasn't "right" to help with, improve, endothelial-dependent FMD. We'll explore potentials in a moment.

Somethign troubling that seems glossed over - the higher blood pressure in those following the low-fat diet - where at baseline their blood pressure averaged 122/75, at 6-weeks it improved to 115/72 and again improved at 12-weeks was similar at 118/70. What happened between the 12-week measure and the blood pressure reading at week 52, when blood pressure was now averaging 130/74?

This is something I would consider worthy of noting, even maybe point out and suggesting additional questions and investigation as to why!

In the discussion section, the researchers stated that "The main finding of the present study was that weight loss on a low-carbohydrate diet which brought about reductions in glucose, insulin and LDL-C did not improve FMD either after short-term weight loss or long-term weight maintenance. Irrespective of diet composition weight loss had beneficial effects in the short term on adhesion molecules and blood pressure and in the longer term on adiponectin and P-selectin. There appears to be a delay in improvement in both adiponectina nd P-selection as these molecules did not improve until weight loss had been maintained for a year."

They went on to add, "Lack of change in FMD in the present study confirms our previous finding that weight loss does not improve FMD...One of our goals with the dietary intervetion was a reduction in LDL-C which we achieves, 18% at 6-weeks and nearly 30% at the end of the study with no effect on FMD."

The researchers also noted that "The present study was also designed to achive a reduction in glucose in a 6-week weight loss intervention on a more moderate diet of 6000kJ and we achieved this but with no effect on FMD."

And, "A complex physiological response such as FMD may be related to LDL and glucose cross-sectionally and in post hoc analyses but these may not be casually related but correlate in some circumstances with the real unmeasured mediator of change. For instance, oxidative stress may be a major factor in reducing NO bioactivity but reducing LDL levels may have no effect on this even though the endothielial cell is clearly heathier as judged by a reduced adhesion molecules."

In the end, they concluded that "weight loss on a low-carbohydrate, low-saturated fat diet, does not improve FMD despite improvement in cardiovascular risk factors. The improvement in adiponectin was delayed."

So what was their error of omission?

Well, for one they failed to note the problematic rise in blood pressure observed in the subjects following the low-fat diet. But, let's set that aside for a moment.

They also failed to note that the above failure to improve FMD was also observed in subjects following the low-fat diet; one that happened to be designed well enough to match the American Heart Association recommendations!

Yet even that low-fat diet (20% of calories from fat) didn't help improve FMD, despite their weight loss, improvement in glucose, insulin and cholesterol; but this was left unsaid.

I'm not surprised.

So, what we're left with is the stated null finding of those on the low-carb diet, with no real statement that neither dietary approach did much for FMD.

I hate to say it, but there was also a lack of curiosity as to why this was.

It's pretty much accepted dogma that a low-fat diet improves the cardiovascular system, thus would exert a postive - significant - effect on endothelial-dependent FMD. It didn't, yet the researchers didn't say "hey, wait, this low-fat diet didn't help either" and instead highlighted that the low-carb diet didn't improve FMD in their conclusions.

Some questions really do need to be asked.

First, how did the low-carb diet look compared with the habitual diet?

We know subjects were consuming, on average, 11.4mJ each day (2725-calories) as their habitual diet. The weight loss diet was 6000kJ each day (1430-calories). They followed the weight loss phase of the diet for six weeks and lost 5.8kg, or 12.75-pounds.

Let's do math!

Each day, we're to believe, the subjects were in a calorie deficit of 1295-calories. Six weeks is 42-days, so over the period, a calorie deficit of 54,390 calories - enough to theoretically lose 15.5-pounds. Hmmm....Okay, so it's pretty clear they did not really follow the diet as planned, since it's clear they consumed more calories than was reported. Happens all the time, no biggie.

Except, we have no idea what the excess calories were, so we have a confounding variable here. Did they eat pie? Did they eat broccoli? Did they eat fatty meat instead of lean meat? Did they skip the oatmeal and eat eggs? Who knows?

It's also noteworthy that the low-fat dieters ate a habitual diet of 10.8mJ daily (2581-calories) and were placed on the same weight loss calorie level. So they were in a calorie deficit of 1150-calories each day, or a six week deficit of 48,342-calories. This theoretically would result in a weight loss of 13.8-pounds; they lost 5.9kg (13-pounds). Did they cheat less? Did they stick to the diet more carefully? Who knows?

But, we can be sure we have a confounding variable here - something doesn't add up, and it looks like that something is calorie intake. It appears it was higher than the dietary protocol called for; and an increased calorie intake we have no idea what foods/macronutrients it came from.

So then, is there anything else? Let's see how macronutrient intake changed on the low-carb diet.

At baseline, their habitual diet - 2725-calories - was from 39.6% carbohydrate (270g), 19.6% protein (133.5g) and 36.5% fat (110.5g). We do not know the baseline intake for fatty acids, but do know the dietary protocol was strict - saturated fat 7%, PUFA 6% and MUFA 13% of calories.So, while following the weight loss diet, the macronutrient profile changed to provide 1430-calories each day, of which 33% were carbohydrate (118g), 40% protein (143g) and 27% fat (43g) with 7% from saturated fat (11.1g), 6% from polyunsaturated fat (9.5g) and 13% from monounsaturated fat (20.7g).

The first glaring disparity is the protein-to-fat intake, for every 1g of fat, they were expected to consume 3.3g of protein; this is a highly unusual pattern, heavy with protein and too lean - if you review other studies on "low-carb" diets, the fat intake is usually higher than the level in this protocol and protein typically lower; of note, this intake ratio is next to impossible without some funky planning. I'd like to know how much soy was a part of this diet? How much of the diet was comprised of non-fat dairy? How much fish was allowed, and what type was it? Were protein shakes or supplements part of the protocol? If so, which type of isolate dominated?

Without this specific data, it's difficult to say one way or another if the foods included may have contributed to the null finding or not.

So here, we have a potential confounding variable that is unexplored.

Anything else?

Well, from the data we do know, it seems we find an inadequate level of polyunsaturated fats - with just 9.5g each day; a level at which the subjects are unable to meet essential requirements for omega-6 or omega-3 fatty acids!

I am really starting to wonder why researchers designing diet protocols that are inadequate for known essential nutrients?

The Institute of Medicine (IOM) clearly states in the Daily Recommended Intake documentation, the MINIMUM required each day from omega-6 is 5% to 10% of calories and the MINIMUM requirement each day from omega-3 is 0.5% to 1% - when calories are adequate to maintain weight. In absolute terms - absolute gram minimums - the IOM states that adequate intake of omega-6 fatty acid is 14g-17g for men (depending on age) and 11g-12g for women (depending on age); and that adequate intake of omega-3 fatty acids is 1.6g for men and 1.1g for women.

Combined, the absolute minimum intake for essential fatty acids is between 15.6g-17.6g for men and 12.1g-13.1g for women.

In this study, even if every last gram of polyunsaturated fat was an omega-3 or omega-6, these subjects were deficient for essential fatty acids with only 9.5g of polyunsaturated fats as part of the diet.

So, again, confounding variable - huge confounding variable!

And the researchers question why the diet didn't have an effect on FMD?

Perhaps the researchers haven't read the data showing improvement in cardiovascular health when essential fatty acid intake is optimized to meet or exceed current recommendations?

Recent evidence of the role of omega-3 polyunsaturated fatty acids on blood pressure control and hypertension-related complications

Omega-3 Fatty Acids: Role in Cardiovascular Health and Disease

Fish Oil and Endothelial Function

I can't say it enough - I love good data, but studies like this, with macronutrient intakes, as percentage of calories, is highly confounded data. Designing a dietary approach to lose weight or maintain weight, macronutrient percentages are often inefficient and do not meet essential nutrient requirements.

I'd really like to see some researchers start designing studies to ensure adequate intake of essential nutrients within the calorie deficits - until we start to look at the nutrient-quality of weight loss diets, I'm afraid we're not going to make much progress to provide the public with sound, scientifically supported recommendations.


  1. Once again Regina you have cut to the chase. And it appears the designers of the study didn't know what continent they were on.

  2. Anonymous7:56 PM

    This is why I read you every day. Your attention to detail and fact is incredibly reassuring for those of us struggling to eat right depite those constant 'sexy' or alarming headlines made in the media. I always enjoy what you have to say and how well you decipher and make sense of all this--and your fairness in reporting this data is extremely refreshing as well.

  3. Anonymous8:44 PM

    I can't be sure from the numbers you quoted, but it looks to me like both groups dropped their total carb intake (due to the large total calorie reduction), and that much of the difference in results is likely due to the low-carb group simply dropping more carbs from their diet than the low-fat group (but with both groups showing improvements).

  4. Like dietking2 said....Post like this are the reason I check your blog every day....and miss you when you go aaway! LOL

    As far as I'm concerned you and Dr mike are the best at explaining these complicated issues.

    Oh yea....I read an artilce today and the nutritionist that wrote it referred to 6 macronutrients we should have daily...would that be counting fat individually and fiber separate?

  5. Oh yea....I read an artilce today and the nutritionist that wrote it referred to 6 macronutrients we should have daily...would that be counting fat individually and fiber separate?


    1. Alcohol
    2. Carbohydrate
    3. Protein
    4. Fat

    Perhaps (stretching it) 5. Fiber

    I'm clueless as to what "6" would be!

  6. Thanks everyone for the kind words!

  7. Anna in San Diego, CA9:45 PM

    #6 is chocolate!

  8. "weight loss on a low-carbohydrate, low-saturated fat diet, does not improve FMD despite improvement in cardiovascular risk factors."

    Low-saturated fat? Why?

  9. Low-saturated fat? Why?

    :::banging hammer over your head:::

    Because, dontcha know saturated fat is going to kill you?


  10. Anonymous2:33 PM

    1 grains
    2 veggies
    3 fruits
    4 dairy
    5 meat
    6 fats/oils

  11. Anonymous6:14 PM

    So, I'm curious if you've ever seen any long-term studies that show measurable results for reversal of heart disease such as with Ornish, and now Esselstyn. I tried the low-carb approach for several years that you all are pushing, and I ended up with high blood pressure, higher cholesterol, reflux, yo-yo weight and plenty of meds. After 4 months of following Dr. Esselstyn's NO added FAT program (vega, no oil, no refined carbs), I've dropped all my meds, have lost 20 pounds, and have ldl below 80. His study is a 20 year study with measurable results for reversing disease in nearly dead heart disease patients. Do you have any evidence whatsoever that low carb can even come close to doing that over the long-term? My guess is that the low fat diets in these studies you are citing are still too high in fat, and that's why you don't see a difference. Read Esselstyn's book and see if you can come up with anything approaching his long-term results. I wish you all well, but your approach was slowly killing me, and I thank God that I found Dr. Esselstyn in time. I'll take 20 years of successful clinical results over these patchwork studies any day. Don't mistake a 20% fat diet rich in animal fats for a real low fat diet. Esselstyn shows that the benefits only come if you completely get rid of all saturated fats. Guess we'll see who's right in 20 years, but I'm going with the study that's already shown results.

  12. Anonymous11:53 AM

    Still waiting for that study that shows low carb can REVERSE heart disease over the long term. Oh, that's right--there aren't any. Lots of random isolated studies showing short-term impacts on this number and that number, but nothing showing verifiable clinical evidence. I just don't see why anyone would pin their health on something that has no clinical basis whatsoever. Good luck all. I think you'll need it.