CR + low or high macronutrients?

[Guest guest]

Hi All,

Should we practice CR with levels that are low or high in the three

macronutrients?

The pdf-available below may address this and many other questions that may be in

our

interest.

First, there is an editorial review of the paper.

O Hill

Obesity treatment: does one size fit all?

Am J Clin Nutr 2005 81: 1253-1254. Editorial

See corresponding article on page 1298.

Those trying to lose weight are quick to embrace the latest popular diet but are

almost as quick to abandon it. This observation is evidenced by the rise and the

apparent recent decline in the popularity of low-carbohydrate, high-fat diets in

the

United States. It is interesting that the public seems ready to abandon these

diets,

despite evidence of their effectiveness. Several randomized controlled studies

have

shown that these diets are effective in producing weight loss and metabolic

improvements over 6 mo in obese patients (1-5). The problem seems to be that the

greater weight loss achieved with these diets is not maintained over time (1,

5). It

is not clear whether this is due to the waning effectiveness of the diet or to

the

inability of most people to maintain this diet.

If history is any indication, the public is now looking for the next popular

weight-loss diet. Most weight-loss diets are based on a particular macronutrient

composition, and the potential combinations are limited. Because low-fat and

low-carbohydrate diets have already been popular choices, one good possibility

is

that a high-protein diet will be the next popular diet (6). If high-protein

diets do

become the " next big thing, " it would be useful to scientifically evaluate the

safety and efficacy of these diets to determine whether they represent another

passing fad or whether they can be a useful tool for weight management.

In this issue of the Journal, Noakes et al (7) report the results of a 12-wk

study

that evaluated high-protein (HP) diets intended for weight loss. They randomly

assigned overweight and obese patients to 2 different hypocaloric diets. Both

diets

were low in fat, but one (HP diet) was higher in protein (34% compared with 17%)

and

lower in carbohydrate (46% compared with 64%) than the other, which was high in

carbohydrate (HC diet). Two important messages emerged from this study. First,

Noakes et al found that the hypocaloric HP diet produced weight loss comparable

to

that of the HC diet and provided nutritional and metabolic benefits that were

equal

to or in some cases greater than those seen with the HC diet. Second, in a post

hoc

analysis, they found that obese subjects in the top 50% of blood triacylglycerol

concentrations at baseline lost more weight with the hypocaloric HP diet than

with

the hypocaloric HC diet. Thus, the study is noteworthy in that it suggests that

high-protein diets are effective at both producing weight loss and improving

risk

factors for diabetes and heart disease and that it may be possible to identify

persons who do particularly well with high-protein diets.

The first message from this study is important but should be interpreted with

caution. Many different types of diets can produce substantial weight loss in

the

short term. Most obese persons attempting to lose weight do not fail in losing

the

weight but rather fail in maintaining the weight loss. We need to know whether

high-protein diets are just alternative ways for some people to achieve weight

loss

(and probably gain it back) or whether they may be useful over the long term. We

need research studies to answer at least 2 important questions: 1) Can

high-protein

diets be maintained permanently? and 2) Can high-protein diets help persons to

permanently maintain their weight loss and the metabolic improvements they

achieve?

Answering these questions will require studies that focus not just on weight

loss

but on the long-term maintenance of weight loss. These studies will be difficult

and

expensive to conduct; however, without them we cannot provide the best advice on

which diet is best for weight maintenance and whether the best diet for

weight-loss

maintenance varies from person to person.

The second message from the study of Noakes et al is that it may be possible to

identify patients who will respond particularly well to high-protein diets. It

is

logical and intriguing to think that we can maximize weight loss by matching

patient

to diet, even though we have little past success in doing so. Noakes et al

speculate

that the reason why their subjects with high triacylglycerol concentrations

responded better to the HP diet was because they were insulin resistant and that

insulin-resistant patients may do better with HP diets. Although this is an

intriguing hypothesis, other measures of insulin resistance apparently do not

predict success in weight loss. Furthermore, whereas triacylglycerol

concentrations

improved more with the HP diet, other factors associated with insulin resistance

(glucose, insulin, and HDL cholesterol) did not. It is important not only that

we

develop a way of predicting who will respond to different diets but also that we

understand why the responses are different. If we understand the mechanisms

involved, we may be more likely to apply this information to individualizing

diet

for weight management. For example, insulin resistance may be the reason that

some

patients do better with high-protein diets, and it is known that people become

more

insulin sensitive with weight loss. Thus, the best diet for maintaining weight

loss

may be different from the best diet for achieving weight loss. It is also

important

to evaluate whether matching patient to diet will not only help maximize weight

loss

during the consumption of hypocaloric diets but will also help maintain weight

loss.

It may be useful to consider weight management as consisting of 2 different

phases:

achieving weight loss and maintaining weight loss. The strategies that work for

losing weight may not be effective for keeping weight off. We have found this to

be

the case in a review of the National Weight Control Registry, which follows 5000

people who have succeeded in maintaining weight loss in the long term (8). When

it

comes to choosing a hypocaloric diet, one size may not fit all. However, keeping

weight off requires the achievement of a permanent balance between energy intake

and

energy expenditure. Here is where physical activity becomes critically important

(8)

and may even be more important than diet composition.

The question remains as to whether high-protein diets are a temporary tool for

helping some people maximize weight loss or whether they represent a reasonable

way

for some people to eat permanently? The study by Noakes et al is a good start in

addressing this question ...

Now, here is the paper for which there is not yet a Medline citation and the

above

presented an editorial.

The same researchers had previously provided the pdf-available:

Luscombe-Marsh ND, Noakes M, Wittert GA, Keogh JB, P, Clifton PM.

Carbohydrate-restricted diets high in either monounsaturated fat or protein are

equally effective at promoting fat loss and improving blood lipids.

Am J Clin Nutr. 2005 Apr;81(4):762-72.

PMID: 15817850

Manny Noakes, B Keogh, R , and M Clifton

Effect of an energy-restricted, high-protein, low-fat diet relative to a

conventional high-carbohydrate, low-fat diet on weight loss, body composition,

nutritional status, and markers of cardiovascular health in obese women

Am J Clin Nutr 2005 81: 1298-1306.

.... Design: The subjects were randomly assigned to 1 of 2 isocaloric 5600-kJ

dietary

interventions for 12 wk according to a parallel design: a high-protein (HP) or a

high-carbohydrate (HC) diet.

Results: One hundred women with a mean (±SD) body mass index (in kg/m2) of 32±6

and

age of 49±9 y completed the study. Weight loss was 7.3±0.3 kg with both diets.

Subjects with high serum triacylglycerol (>1.5 mmol/L) lost more fat mass with

the

HP than with the HC diet (±SEM: 6.4±0.7 and 3.4±0.7 kg, respectively; P = 0.035)

and

had a greater decrease in triacylglycerol concentrations with the HP (–0.59±0.19

mmol/L) than with the HC (–0.03±0.04 mmol/L) diet (P = 0.023 for diet x

triacylglycerol interaction). Triacylglycerol concentrations decreased more with

the

HP (0.30±0.10 mmol/L) than with the HC (0.10±0.06 mmol/L) diet (P = 0.007).

Fasting

LDL-cholesterol, HDL-cholesterol, glucose, insulin, free fatty acid, and

C-reactive

protein concentrations decreased with weight loss. Serum vitamin B-12 increased

9%

with the HP diet and decreased 13% with the HC diet (P < 0.0001 between diets).

Folate and vitamin B-6 increased with both diets; homocysteine did not change

significantly. Bone turnover markers increased 8–12% and calcium excretion

decreased

by 0.8 mmol/d (P < 0.01). Creatinine clearance decreased from 82±3.3 to 75±3.0

mL/min (P = 0.002).

Conclusion: An energy-restricted, high-protein, low-fat diet provides

nutritional

and metabolic benefits that are equal to and sometimes greater than those

observed

with a high-carbohydrate diet.

INTRODUCTION

.... a positive health benefit from a high protein intake was observed in the

Nurses'

Health Study, which found a 26% lower rate of cardiovascular disease in those

women

in the highest protein intake group than in those in the lowest protein intake

group

(1). Clinical intervention studies have provided sound evidence that an ad

libitum

high-protein diet from mixed sources in free-living overweight people increases

the

amount of weight lost in a 6-mo weight-loss program (by 3.8 kg) compared with a

high-carbohydrate diet by enhancing satiety (2). Furthermore, weight-loss

studies in

overweight women have shown that diets with a high ratio of protein to

carbohydrate

have positive effects on markers of disease risk, including body composition,

blood

lipids, and glucose homeostasis, and that these benefits may be mediated partly

by

the effect of protein on satiety and by a lower glycemic load because of a lower

carbohydrate intake (3, 4). A higher protein intake during weight loss may also

prevent some of the inevitable loss of lean body mass and, thus, may enhance

insulin

sensitivity (5, 6), although this has not been observed at very low energy

intakes

(7). In 2 studies in overweight men and women, with either insulin resistance or

type 2 diabetes, we showed that a high-protein weight-loss diet (28–30% of

energy

from protein) from mixed sources enhances fat loss by 1–2 kg over 12 wk,

particularly in women, compared with an isocaloric high-carbohydrate weight-loss

diet (8, 9). It is known that different protein sources have different effects

on

the release of insulin (10, 11), and this may be important to the mechanism of

action of both the enhanced satiety (Latner and Schwartz 1999) and the

differential

fat loss. However, foods and dietary patterns high in protein may vary in

saturated

fat and nutritional composition, and concerns have been raised regarding the

effect

of high-protein diets on serum lipids and subsequent cardiovascular disease

risk.

Evidence also exists that high-protein diets enhance calcium excretion and

increase

bone loss, which particularly needs clarification (12).

The purpose of the study was to determine the effect of reduced caloric intake,

associated with higher dietary protein from low saturated fat sources compared

with

a high-carbohydrate diet, on weight loss, body composition, cardiovascular

disease

risk, nutritional status, and markers of bone turnover in overweight and obese

women. We hypothesized as our primary outcome that the high-protein diet would

enhance fat loss and minimize lean mass loss compared with the high-carbohydrate

diet.

SUBJECTS AND METHODS

Subjects

.... subjects had to be females between 20 and 65 y of age, have a body mass

index

(BMI; in kg/m2) between 27 and 40, and have no history of metabolic disease or

type

1 or type 2 diabetes.

.... Nineteen women withdrew from the study before completion, 6 in the

high-protein

group and 13 in the high-carbohydrate group.

Study design

The subjects were randomly assigned to 1 of 2 isocaloric 5600-kJ dietary

interventions for 12 wk according to a parallel design: 1) a high-protein,

low-saturated-fat dietary pattern [HP group; 34% of energy from protein, 20%

from

fat (<10% from saturated fat) and 46% from carbohydrate] and 2) a

high-carbohydrate,

low-saturated-fat dietary pattern [HC group; 17% of energy from protein, 20%

from

fat (<10% from saturated fat), and 64% from carbohydrate].

... The foods prescribed to obtain the planned dietary intakes in both diet

groups

are outlined in Table 2. The total energy content of each diet was initially

5600

kJ, but was adjusted upward for very active subjects so that weight loss would

be 1

kg/wk for the first 2–3 wk. ...

TABLE 2 Prescriptive food composition of the test diets 1

----------------------------

----HP diet HC diet

-------------------------------

Cereal 25 g bran cereal + 15 g wheat-flake breakfast biscuit 40 g wheat-flake

breakfast biscuit

Milk 250 mL/d (<1% fat) 250 mL/d (<1% fat)

Low-fat yogurt 200 g Nil

Lean meat, poultry, or fish 200 g lean beef or lamb >6 times/wk + extra 100 g

other

protein food daily (lunch) 80 g chicken, pork, or fish (>6 times/wk) + red meat

<1

time/wk

Fresh fruit 300 g 450 g

Pasta, rice Nil 120 g cooked (6 times/wk)

Salad 100 g 100 g

Vegetables 400 g 400 g

Canola oil 15 g 15 g

Whole-grain bread 70 g 105 g

Biscuits Nil 2 shortbread biscuits

Wine or equivalent (optional) 300 mL/wk 300 mL/wk

--------------------------------

1 HP, high protein; HC, high carbohydrate.

.... RESULTS

Dietary intakes

The self-reported composition of the study diets consumed during the 3-mo study

period is presented in Table 3. There were no significant differences in total

energy, alcohol, and dietary fiber intakes between the diet groups. Total,

saturated, and monounsaturated fat intakes were significantly lower in the HC

group,

as was the dietary cholesterol intake. Intakes of the micronutrients thiamine,

riboflavin, niacin equivalents, calcium, and iron were significantly higher in

the

HP group.

TABLE 3 Reported dietary intake data assessed by weighed food records 1

----------------------------

----HP diet (n = 52) HC diet (n = 47) P 2

-----------------------------

Energy (kJ) 5310±55.5 3 5219±78.6 NS

Protein (% of energy) 31.3±0.24 17.8±0.21 <0.001

Fat (% of energy) 22.1±0.40 20.1±0.52 0.003

Carbohydrate (% of energy) 44.2±0.42 60.8±0.58 0.000

Alcohol (% of energy) 1.1±0.24 1.1±0.26 NS

Fiber (g) 27.6±0.58 26.1±0.58 NS

Cholesterol (mg) 216±4.8 78±4.6 <0.001

Saturated fat (% of energy) 5.4±0.17 4.6±0.23 0.003

Monounsaturated fat (% of energy) 9.4±0.20 8.3±0.26 0.001

Polyunsaturated fat (% of energy) 4.7±0.11 4.7±0.14 NS

Vitamin A equivalent (µg) 1109±53.9 1149±48.4 NS

Vitamin C (mg) 111±4.6 122±7.0 NS

Thiamine (mg) 1.6±0.02 1.4±0.03 <0.001

Riboflavin (mg) 2.6±0.04 1.5±0.03 <0.001

Niacin equivalent (mg) 48.0±0.43 26.9±0.42 <0.001

Calcium (mg) 777±14.7 594±9.8 <0.001

Iron (mg) 14.8±0.20 9.6±0.22 <0.001

----------------------------------------

1 HP, high protein; HC, high carbohydrate.

2 Unpaired two-tailed t test between dietary treatments.

3 ±SEM over 9 d (all such values).

Weight and fat loss

The subjects that dropped out were aged 37±8 y, which was significantly younger

than

those who completed the study (P < 0.001), but BMI was not significantly

different

between groups (P = 0.196). When we undertook an intention-to-treat analysis,

with

baseline weight carried forward for dropouts, there was a significant main

effect of

diet for weight loss (HP diet: 6.8±3.9 kg; HC diet: 5.4±4.3 kg; P = 0.041). When

the

analysis was carried out by using the last weight carried forward for dropouts,

the

diet effect was weakened (HP diet: 7.0±3 kg; HC diet: 5.8±4.0 kg; P = 0.066).

However, we believe that a " completers " analysis was a more conservative and

appropriate assessment of our data because this was a controlled clinical trial

to

examine the metabolic effects of dietary composition. The subjects who completed

the

12-wk trial (n = 100) had a mean weight loss of 7.6±0.4 kg with the HP diet (n =

52)

and 6.9±0.5 kg with the HC diet (n = 48); these values were not significantly

different from each other (P = 0.29). There were 84 subjects with weight losses

>4

kg. However, there was no statistically significant difference in weight loss or

in

the number of subjects achieving >4 kg weight loss by diet. When a subgroup

analysis

was conducted, there was a significant interaction with diet and weight loss

according to triacylglycerol status (P = 0.032). Triacylglycerol status was

categorized about the median of 1.5 mmol/L.

Weight loss was 25% greater with the HP diet in subjects with a triacylglycerol

concentration >1.5 mmol/L (P = 0.005), whereas there was no differential effect

of

diet in women with a low triacylglycerol concentration (Table 4).

TABLE 4 Interaction between diet and triacylglycerol (TG) status for weight loss

1

----------------------------------------

Diet and TG status TG concentration Baseline weight Weight loss

----------------------------------------

----mmol/L kg kg

----------------------------------------

HP diet

TG < 1.5 mmol/L (n = 27) 0.89±0.04 89.1±2.8 7.3±0.8

TG > 1.5 mmol/L (n = 25) 1.89±0.16 85.4±1.6 7.9±0.4

HC diet

TG < 1.5 mmol/L (n = 23) 0.90±0.04 86.5±2.6 8.1±0.7

TG > 1.5 mmol/L (n = 25) 1.99±0.13 86.2±2.5 5.8±0.7 2

-------------------------------------

1 All values are ±SEM. HP, high protein; HC, high carbohydrate. There was no

significant difference in baseline weight by diet or TG-status.

There was a significant interaction between diet and TG status (P = 0.032) by

repeated-measures ANOVA, with diet and TG status as between-subject factors. The

main effect of neither TG status (P = 0.227) nor the main effect of diet (P =

0.286)

was significant.

2 Significant difference for change between diets (P = 0.005) by univariate

analysis, with baseline BMI as a covariate.

Similarly, the DXA data showed no overall effect of diet composition on total

fat

loss (P = 0.16; Table 5), but a significant interaction was observed with diet

and

triacylglycerol status on total (P = 0.019) and midriff (P = 0.03) fat. In women

with high triacylglycerol concentrations, the total fat loss was 6.4±0.7 kg in

the

HP group and 3.4±0.7 kg in the HC group (P = 0.035 for diet difference; Figure

2).

The amount of weight lost specifically from the midriff area in the HP group was

twice that in the HC group, but the difference was not statistically significant

by

post hoc analysis across the 4 groups (1.0±0.2 kg compared with 0.5±0.1 kg; P =

0.12).

TABLE 5 Body-composition changes assessed by dual-energy X-ray absorptiometry 1

---HP group (n = 52) HC group (n = 48)

---------------------------------------------------

Total lean mass (kg) 2

Week 0 41.8±0.8 40.9±0.9

Week 12 40.3±0.9 39.3±1.0

Change –1.5±0.3 –1.8±0.3

Total fat mass (kg) 2

Week 0 42.1±1.2 41.9±1.1

Week 12 36.5±1.1 37.1±1.1

Change 3 –5.7±0.6 –4.5±0.5

Midriff lean fat (kg) 2

Week 0 2.4±0.1 2.5±0.1

Week 12 2.2±0.1 2.4±0.1

Change –0.2±0.1 –0.2±0.1

Midriff fat (kg) 2

Week 0 3.6±0.1 3.7±0.2

Week 12 2.7±0.1 3.0±0.1

Change 3 –0.9±0.1 –0.7±0.1

---------------------------------------------------

1 All values are ±SEM. HP, high protein; HC, high carbohydrate. There were no

significant differences at baseline between diets.

2 Main effect of time (P < 0.01) by repeated-measures ANOVA with both time

points as

within-subject variables over both treatments.

3 There were no significant main effects of diet or triacylglycerol status, but

there was a significant diet x triacylglycerol status interaction for total fat

(P =

0.019) and midriff fat (P = 0.03) by repeated-measures ANOVA with diet and

triacylglycerol status as between-subject factors. See Figure 2 for subgroup

analysis.

Serum and urinary urea, creatinine, and creatinine clearance

The urea-creatinine ratio in urine as well as serum urea were both significantly

different by diet (P = 0.003 and P < 0.001, respectively; Table 6). Creatinine

clearance decreased with weight loss, from 82±3.3 75±3.0 mL/min (8%; P = 0.002),

with no significant difference between the diets (P = 0.346). There was no

significant change in serum creatinine (74.0±0.9 µmol/L at baseline compared

with

75.4±0.8 µmol/L at week 12); therefore, the difference was due to the amount of

creatinine excreted in the urine—from 8.9±0.32 to 8.1±0.21 mmol/d. There was no

correlation between weight loss and change in creatinine clearance or creatinine

excretion. However, adjustment for the change in weight rendered the change in

clearance insignificant (P = 0.621), ie, the change in calculated creatinine

clearance was due to the weight change and not to a change in renal function.

TABLE 6 Markers of renal function 1

-------------------------------------------------------

-----Week 0 Week 12

-------------------------------------------------------

Urine urea:creatinine

HP group (n = 50) 33.7±1.29 38.2±0.88 2

HC group (n = 48) 32.5±1.5 34.2±1.2

Serum urea (mmol/L)

HP group (n = 50) 5.5±0.2 6.2±0.2 3

HC group (n = 48) 5.8±0.2 5.1±0.2

Creatinine clearance (mL/min) 4

HP group (n = 50) 82.3±3.3 76.7±2.9

HC group (n = 48) 81.9±3.3 72.9±3.1

---------------------------------------------------------------

1 All values are ±SEM. HP, high protein; HC, high carbohydrate. There were no

significant differences at baseline between diets.

2 Significantly different from HC group, P = 0.003 (univariate analysis at week

12

with week 0 as covariate).

3 Significantly different from HC group, P < 0.001 (univariate analysis at week

12

with week 0 as covariate).

4 No significant difference between diets, P = 0.346 (univariate analysis at

week 12

with week 0 as covariate).

Lipids, glucose, insulin, fatty acids, and C-reactive protein

There was no significant effect of diet composition on LDL-cholesterol,

HDL-cholesterol, and glucose concentrations (Table 7). LDL cholesterol decreased

overall by 6%, HDL cholesterol decreased by 7%, and glucose concentrations

decreased

by 4% with both diets. Diet composition affected the decrease in

triacylglycerols,

which decreased by 8% with the HC diet and by 22% with the HP diet (P = 0.007).

Because subjects with high triacylglycerol concentrations may be more responsive

to

factors that alter triacylglycerols, we reanalyzed the data according to

triacylglycerols status (above or below the median of 1.5 mmol/L). There was a

diet

x triacylglycerol status interaction for triacylglycerol (P = 0.023). In the

women

with a high triacylglycerol concentration, the HP diet lowered triacylglycerols

significantly, by 28% compared with only 10% with the HC diet. In the low-

triacylglycerol group, there was no significant effect of diet composition on

triacylglycerol (Figure 3). Fasting glucose, insulin, and free fatty acid

concentrations all decreased significantly with weight loss, with no

differential

effect of diet composition (Table 7). CRP decreased significantly overall, by

19% (P

< 0.001), with no significant effect of diet (P = 0.447). The change in CRP in

the

low- triacylglycerol group was 0.74±0.27 mg/L, and the change in the high-

triacylglycerol group was 1.90±0.41 mg/L (P = 0.03 for the difference). This

difference was enhanced (P = 0.018) after adjustment for weight loss.

TABLE 7 Fasting lipid, glucose, insulin, free fatty acid, and C-reactive protein

(CRP) concentrations 1

--------------------------------------------------------------

----Week 0 Week 4 Week 8 Week 12 Change P for diet 2 P for time 3

--------------------------------------------------------------

Triacylglycerol (mmol/L) 4

HP group 1.37±0.11 5 1.08±0.06 1.10±0.06 1.07±0.06 –0.30±0.10 — —

HC group 1.47±0.11 1.31±0.09 1.3±0.09 1.35±0.10 –0.11±0.06 0.007 <0.001

Total cholesterol (mmol/L)

HP group 5.75±0.16 4.97±0.14 5.14±0.14 5.26±0.15 –0.48±0.10 — —

HC group 5.88±0.14 5.12±0.14 5.26±0.15 5.54±0.15 –0.33±0.08 0.164 <0.001

LDL cholesterol (mmol/L)

HP group 3.79±0.14 3.32±0.13 3.43±0.13 3.53±0.13 –0.26±0.09 — —

HC group 3.90±0.12 3.39±0.12 3.51±0.13 3.71±0.13 –0.19±0.08 0.399 <0.001

HDL cholesterol (mmol/L)

HP group 1.33±0.05 1.17±0.04 1.21±0.04 1.25±0.04 –0.09±0.02 — —

HC group 1.32±0.04 1.15±0.03 1.17±0.04 1.22±0.04 –0.09±0.02 0.657 <0.001

Glucose (mmol/L)

HP group 6.16±0.65 6.00±0.59 6.13±0.66 5.93±0.61 –0.21±0.05 — —

HC group 6.08±0.58 5.97±0.53 6.00±0.54 5.83±0.62 –0.25±0.07 0.589 <0.001

Insulin (mU/L)

HP group 10.0±0.9 7.2±0.5 7.4±0.7 7.3±0.5 –2.7±0.5 — —

HC group 10.0±0.7 7.5±0.5 7.9±0.8 8.4±1.2 –1.6±0.9 0.278 <0.001

Free fatty acids (mmol/L)

HP group 0.46±0.03 0.45±0.03 0.39±0.02 0.42±0.03 –0.04±0.03 — —

HC group 0.41±0.02 0.43±0.02 0.37±0.02 0.39±0.02 –0.02±0.02 0.765 <0.001

CRP (mg/L)

HP group 6.6±0.7 — — 4.9±0.6 –1.7±0.4 — —

HC group 4.8±0.5 — — 4.0±0.4 –0.8±0.3 0.447 <0.001

------------------------------------------------

1 HP, high protein (n = 52); HC, high carbohydrate (n = 48). There were no

significant differences in variables at baseline between diets.

2 Main effect of diet by univariate analysis at week 12 with diet as the fixed

factor and the week 0 data point as the covariate.

3 Main effect of time by repeated-measures ANOVA with all time points as

within-subject variables over both treatments.

4 Significant diet x triacylglycerol status interaction (P = 0.023) by

repeated-measures ANOVA with all time points and diet and triacylglycerol status

as

between-subject factors. See Figure 3 for subgroup analysis.

5 ±SEM (all such values).

Iron status

There was a small but nonsignificant 2% increase in hemoglobin with the HP diet

(P =

0.116) but no change with the HC diet (Table 8). Transferrin decreased by 9–12%

with

both diets. There were no significant changes in iron status. Ferritin

concentrations were outside the normal range of 150 µg/L in 17 subjects, which

suggested that iron stores were likely to be replete and nonresponsive to

dietary

changes. When these subjects were excluded from the analysis, there was a

significant 41% increase in serum ferritin in the HP group but no change in this

marker of iron stores in the HC group (P = 0.004 for diet effect; Figure 4). It

is

interesting to note that ferritin, which has been argued to be an additional

marker

for metabolic syndrome, was positively correlated with serum homocysteine

concentrations at baseline (r = 0.209, P = 0.037).

TABLE 8 Iron status, vitamin status, and markers of bone turnover 1

------------------------------

----Week 0 Week 12 Change P for diet 2 P for time 3

----------------------------------

Hemoglobin (g/L)

HP group 132±1 4 5 135±1 3±1 — —

HC group 138±1 138±1 0±1 0.116 0.066

Transferrin (µmol/L)

HP group 34.3±0.9 30.3±0.8 –4.1±0.4 — —

HC group 34.0±0.9 30.8±0.9 –3.1±0.5 0.148 <0.001

Transferrin saturation (%)

HP group 23.9±1.3 24.6±1.3 0.6±1.2 — —

HC group 27.0±1.3 27.9±1.2 0.4±1.4 0.383 0.554

Ferritin (µg/L)

HP group 105±23 120±17 15±10 — —

HC group 83±9 90±12 7±6 0.144 0.064

Iron (µmol/L)

HP group 16.0±0.7 6 14.6±0.6 –1.1±0.6 — —

HC group 18.0±0.9 16.2±0.6 –1.8±0.9 0.267 0.010

Serum vitamin B-12 (pmol/L)

HP group 273±14 311±21 38±13 — —

HC group 278±14 240±13 –38±7 <0.0001 0.865

Pyridoxyl phosphate activation (%)

HP group 50.3±1.4 47.0±1.0 –3.1±1.2 — —

HC group 47.3±1.7 44.9±1.5 –2.4±1.0 0.602 0.001

Serum homocysteine (µmol/L)

HP group 8.5±0.2 8.5±0.2 0.1±0.2 — —

HC group 8.8±0.3 8.7±0.2 0.1±0.2 0.733 0.596

Serum folate (nmol/L)

HP group 26.3±1.0 26.7±0.7 0.4±0.9 — —

HC group 24.8±1.1 27.1±0.7 2.3±0.9 0.265 0.045

Serum osteocalcin (ng/mL)

HP group 6.75±0.56 7.95±0.46 1.20±0.3 — —

HC group 5.49±0.49 7.03±0.48 1.54±0.3 0.997 <0.0001

Deoxypyridinoline:creatinine (nmol/mmol)

HP group 22.2±1.4 24.7±1.0 2.5±1.1 — —

HC group 20.5±0.9 24.2±1.3 3.7±1.0 0.786 <0.0001

Pyridinolone:creatinine (nmol/mmol)

HP group 78.7±5.3 84.3±2.8 5.6±4.0 — —

HC group 69.3±2.4 77.6±3.1 8.2±2.1 0.493 0.003

-------------------------------------

1 HP, high protein (n = 52); HC, high carbohydrate (n = 48).

2 Main effect of diet by univariate analysis at week 12 with diet as the fixed

factor and the week 0 data point as the covariate.

3 Main effect of time by repeated-measures ANOVA with both time points as

within-subject variables over both treatments.

4 ±SEM (all such values).

5,6 Significantly different from HC group:

5 P = 0.004,

6 P = 0.045.

Vitamins B-12 and B-6, homocysteine, and folate

Vitamin B-12 rose significantly (by 9%) with the HP diet, whereas it decreased

(by

13%) with the HC diet (Table 8). The difference between diets was significant (P

<

0.0001). Vitamin B-6 increased with both diets, with no significant difference

between them, whereas homocysteine did not change significantly over the

intervention. Serum folate increased marginally with time (P = 0.045), with no

effect of diet composition (P = 0.234 for diet).

Markers of bone turnover

Osteocalcin increased by 23%, with no significant difference between dietary

interventions (Table 8). There was no correlation between the amount of weight

lost

and changes in urinary crosslinks or the calcium-creatinine ratio. The urinary

crosslinks and the calcium-creatinine ratio, however, were inversely related (r

=

0.36 for pyridinoline and r = 0.28 for deoxypyridinoline), ie, the greater the

decrease in calcium excretion, the smaller the increase in crosslink excretion.

Changes in crosslinks or osteocalcin were unrelated to menopausal or

triacylglycerol

status.

Osteocalcin at week 12 was correlated with the urinary crosslinks at week 12 (P

<

0.01) after the adjustment for baseline osteocalcin, but was not related to

weight

changes (P = 0.723). However, the urinary crosslinks at week 12 were both

correlated

with the change in weight (P < 0.01) and in osteocalcin (P < 0.05) after the

adjustment for baseline values. This suggests that weight loss drives increased

bone

loss and there is partial compensation with increased bone formation.

DISCUSSION

Although we hypothesized that the HP diet would result in greater fat loss and

less

lean mass loss than the HC diet, we did not observe this for the group of

overweight

women overall. This finding contrasts with that of our previous studies in

subjects

with type 2 diabetes (8) and hyperinsulinemia (9), hence, our subgroup analysis

to

ascertain whether markers of the insulin resistance syndrome may have predicted

responses to the dietary interventions. In our study, overweight women with high

triacylglycerol concentrations, one of the key markers of the insulin resistance

syndrome, lost 50% more total fat with the HP diet than with the HC diet.

Although

further confirmation is required, we believe that this is the first study to

suggest

a phenotype x diet interaction with respect to the magnitude of weight loss to

different diet interventions. Although we speculate that the HP diet provided

increased satiety and, hence, subsequent lower energy intake, there was no

suggestion of this from reported dietary intakes or differences in physical

activity

between groups. In a study by ston et al (15), subjects who consumed an

energy-restricted dietary pattern providing 30% of energy from protein reported

less

hunger than did those who consumed a high-carbohydrate dietary pattern. However,

we

cannot rule out the likelihood that the food records may not be suitably

accurate to

detect a difference of 100 kJ/d between groups, which is the extra energy

deficit

needed to result in a 1.9-kg weight difference over 12 wk. The mechanism for why

this was observed only in the group with elevated triacylglycerol concentrations

is

of interest. McLaughlin et al (16) showed that the use a cutoff of 1.47 mmol/L

is

useful in identifying overweight persons who are insulin resistant. However,

they

showed no differences in weight loss with a hypocaloric diet, on the basis of

the

degree of insulin resistance (17). A high triacylglycerol concentration may be a

marker for the ß2-adrenoceptor Gln27Glu polymorphism (18). ß-Adrenergic

receptors

play an important role in the regulation of energy expenditure and lipid

mobilization. A Gln27Glu polymorphism in the ß2-adrenergic receptor gene has

been

shown to be associated with several indexes of obesity in a female, white

population, and obesity was shown to be significantly more prevalent in

high-carbohydrate consumers with this polymorphism (19). In addition, both

lipolysis

and fat oxidation appear to be blunted in obese polymorphic Glu27Glu subjects

(20),

which suggests a rationale for the enhanced fat loss in our subgroup with high

triacylglycerol concentrations who consumed the lower-carbohydrate HP diet.

Concerns that diets high in meat protein may have deleterious effects on renal

function and bone turnover were not substantiated by this study, which showed

similar reductions in creatinine clearance with both dietary patterns as a

consequence of body mass change. Skov et al (21) assessed changes in renal

function

by measuring the glomerular filtration rate during high-protein and

high-carbohydrate diets over a 6-mo period and also concluded that the HP diet

had

no adverse effects on kidney function. ston et al (15) observed that

creatinine

clearance was not altered by dietary protein in the context of weight loss, and

nitrogen balance was more positive in subjects who consumed the HP diet than in

those who consumed the HC diet. Whether this is also true in subjects with

compromised kidney function has not been studied, although we have shown an

improvement in microalbuminuria in subjects with type 2 diabetes after weight

loss

with either a high-protein or a high-carbohydrate diet, which suggests that

weight

loss and consequent blood pressure reduction may be more important in

ameliorating

renal function than is dietary protein. Last, although the amount of dietary

protein

was proportionally high, it was not high in absolute terms. The HP diet provided

104

g and the HC diet provided 58 g protein, which is within the range of protein

intakes in the Australian population (22). In fact, these intakes represent the

95th

percentile and the 20th percentile of protein intakes for women of this age

group in

Australia.

The effect of this level of protein on markers of bone turnover was similarly

not

deleterious. Although weight loss appears to enhance both bone breakdown and,

secondarily, bone formation, these variables were not significantly different

between the 2 diet groups. Other studies have shown that diet-induced weight

loss in

postmenopausal women is associated with general bone loss, probably because of

reduced mechanical strain on the skeleton (23), but that premenopausal women do

not

lose bone even if they have a low calcium intake during weight loss (24).

Evidence

also indicates that higher protein intakes, particularly higher animal protein

intakes, are associated with decreased bone loss in older persons (25). The

reduction in urinary calcium in this study was also unusual because dietary

protein

metabolism is associated with increased urinary calcium (26). The high vegetable

consumption with both dietary patterns may have prevented this because high

vegetable intakes have been shown to decrease urinary calcium (27). An increase

in

calcium excretion was observed with the consumption of a high-protein diet in

the

study by ston et al (15), who state that this was due to the high calcium

content of the high-protein diet in this study. However, we did not observe this

in

other studies of high-protein patterns in which dietary calcium was very high,

ie,

2400 mg/d (28).

Cardiovascular disease markers improved with weight loss with both diets;

triacylglycerol concentrations decreased more with the HP diet in women with

elevated triacylglycerol concentrations. This finding reflects a lower

carbohydrate

load with the HP diet, which results in reduced VLDL TG production (29). CRP,

which

is known to decrease with weight loss (30), was not influenced by dietary

composition, although there was a suggestion that the HP diet lowered CRP more

effectively in women with higher triacylglycerol concentrations. This

observation

warrants further investigation.

Dietary patterns intended for weight loss, which sustain or improve nutritional

status, are important for optimum health. The HC diet pattern was designed to

provide a contrasting intake of protein and, as such, did not fully meet the

recommended dietary allowance (RDA) for some nutrients, notably calcium and

iron. In

contrast, nutrient intakes with the HP diet were adequate or exceeded the RDA,

which

reflected the higher proportion of nutrient-dense protein foods from dairy foods

and

lean meat in the diet. Hemoglobin concentrations were maintained with both

diets.

This is in contrast with the findings of Kretsch et al (31), who fed dieting

obese

women dietary iron at twice the US RDA—half of which was from food and half of

which

was from an oral supplement—yet found a significant reduction in hemoglobin

concentrations. This group also found that hemoglobin and transferrin saturation

were both positively correlated with mean performance on a measure of sustained

attention. The stability of iron status in the HC group was surprising given

both

the quantitatively lower iron intake and the theoretically lower bioavailability

of

iron with this diet, but the higher fruit and vegetable intake may have

contributed

to optimizing iron absorption.

Pyridoxal phosphate activation, a marker of vitamin B-6 status, decreased with

weight loss with both diets, which indicated improved vitamin B-6 status.

Vitamin

B-6 functions as a cofactor in enzymes involved in transamination reactions

required

for the synthesis and catabolism of the amino acids as well as in glycogenolysis

as

a cofactor for glycogen phosphorylase. Vitamin B-6 is found in a wide variety of

foods, including beans, meat, poultry, fish, and some fruit and vegetables.

Improved

vitamin B-6 status is likely to be a function of the improved nutrient density

of

both dietary patterns compared with baseline eating patterns.

The greatest difference in nutrient status was observed with serum vitamin B-12,

which increased by 9% with the HP diet but decreased by 13% with the HC diet.

This

finding reflected the difference in animal protein sources between the 2 dietary

patterns. Ames (32) postulated that micronutrient deficiencies are a major cause

of

DNA damage by the same mechanism as radiation and many chemicals. Intervention

studies in humans have shown that DNA damage is minimized when, among other

micronutrients such as folate, serum concentration of vitamin B-12 are >300

pmol/L,

which is precisely the concentration achieved with the HP diet in this study

without

supplementation.

In conclusion, both the HP and HC, which were intended for weight loss, resulted

in

significant improvements in markers of cardiovascular disease risk, although the

HP

diet resulted in a greater reduction in triacylglycerol concentrations and

improvements in hemoglobin and vitamin B-12 status. An energy-restricted diet

high

in protein from lean red meat and low-fat dairy products seems to provide a

weight

loss advantage in subjects with elevated triacylglycerol concentrations—a marker

of

the metabolic syndrome. This finding requires confirmation in future studies in

hypertriglyceridemic women. There was no evidence of adverse effects on bone or

renal metabolism with either diet over the 12-wk study period.

Al Pater, PhD; email: old542000@...

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