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Volume 88 . Number 1 . July 1, 2001

2001 The American College of Cardiology

 

 

 

 

 

 

 

 

Metabolic effects of high-protein, low-carbohydrate diets

 

 

Margo A. Denke, MD a

 

 

--

a Division of Endocrinology and Center for Human Nutrition

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, USA

 

--

Address for reprints: Margo A. Denke, MD, Center for Human Nutrition, The

University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines

Boulevard, Dallas, Texas 75390-9052

E-mail address: mdenke

 

Manuscript received January 16, 2000; revised manuscript received January

6, 2001, accepted January 6, 2001

PII S0002-9149(01)01586-7

 

Weight-losing diets appeal to the growing population of overweight Americans.

Fad diets promise rapid weight loss, easy weight loss, limited restrictions on

portion sizes of favorite foods, and above all an enhanced sense of well being.

The popularity of fad diets points out the honest promises of traditional weight

loss diets. Traditional weight loss diets promise slow weight loss of 0.45 to

0.9 kg/week. The weight loss is nothing but easy, because portion sizes of

nearly all foods except low-calorie " free foods " must be continuously evaluated

and tracked. Claiming an enhanced sense of well being is hardly appropriate for

a traditional diet-most patients report dissatisfaction from the constant

vigilance over dietary intake. Through discipline and perseverance, traditional

weight loss programs try to teach a patient a new lifestyle of healthy eating.

Unfortunately, 70% of successful weight losers return to their old habits and

within 2 years regain at least half of the weight lost. These patients typically

have little insight into the reasons why the weight was regained, and consider

themselves " failures " to traditional diet programs. They become prime targets

for diets promising rapid and easy weight loss.

 

Prototypes of the high-protein, low-carbohydrate diets

High-protein, low-carbohydrate diets have a long history of cyclic popularity.

Greek Olympians ate high meat, low vegetable diets >2,000 years ago to improve

athletic performance. Dr. William Harvey recommended a diet prohibiting sweet

and starchy foods and permitting ad lib consumption of meats for patients who

needed diuresis. As the basic understanding of nutrition and essential vitamins

developed, these diets fell out of favor. They regained popularity in the late

1960s and early 1970s with the publication of the Atkins' Diet, Stillman's Diet,

The Drinking Man's Diet, the Scarsdale Diet, and the Air Force Diet. The

American Medical Association strongly criticized these diets,[1] leading to

their submergence on the popular diet trend.

 

Resurgence of low carbohydrate diets has been fueled by rising obesity and

insulin resistance in the general population. Although the Atkins' Diet is the

prototype of the low carbohydrate diet, The Sugar Busters Diet, Carbohydrate

Addicts Diet, Protein Power Diet, and the Zone Diet are all variations on this

common theme.

 

Several diets promise that, as long as you restrict carbohydrates, you will lose

weight and you can eat as much food as you want. There may be a kernel of truth

to this claim. For some patients, high-protein intake suppresses appetite.[2]

For other patients, ketosis from carbohydrate restriction suppresses appetite.

Restricting carbohydrate eliminates some popular foods that are often consumed

in excess such as bread, cereal, soft drinks, french fries, and pizza. By simply

excluding carbohydrate foods, patients following the Atkins diet typically

consume 500 fewer calories a day.[3]

 

How low-carbohydrate diets produce initially greater weight loss

Reducing caloric intake by 500 kcal/day should result in a 0.45- to 0.9-kg

weight loss each week. However, low-carbohydrate, high-protein diets typically

produce a 2- to 3-kg weight loss in the first week. This added weight loss is

not due to the miracle of " switching the body's metabolism over to burning fat

stores. " It is due to a diet-induced diuresis. When carbohydrate intake is

restricted, 2 metabolic processes occur, both of which simultaneously reduce

total body water content. The first process is mobilization of glycogen stores

in liver and muscle. Each gram of glycogen is mobilized with approximately 2 g

of water. The liver stores approximately 100 g of glycogen and muscle has 400 g

of glycogen. Mobilization glycogen stores result in a weight loss of

approximately 1 kg. Patients notice this change as a reduction in symptoms of

" bloating " and are very pleased with the effect. The second process is

generation of ketone bodies from catabolism of dietary and endogenous fat.

Ketone bodies are filtered by the kidney as nonreabsorbable anions.[4] Their

presence in renal lumenal fluids increase distal sodium delivery to the lumen,

and therefore increase renal sodium and water loss.

 

In a study comparing an 800-calorie mixed diet with an 800-calorie

low-carbohydrate, high fat diet,[5] 10-day weight loss was 4.6 kg on the

ketogenic diet and 2.8 kg on the mixed diet. Energy-nitrogen balanced studies

documented that the difference in weight lost was all accounted for by losses in

total body water.

 

Long-term weight loss is influenced by caloric restriction, not carbohydrate

restriction

The diuretic effect of low-carbohydrate intake is limited to the first week of

the diet. The remaining weight loss is a function of the laws of energy balance.

Calories from any source determine the success of additional weight loss.

 

In the only published study of Atkins diet, patients following the diet reduced

caloric intake by 500 kcal/day. The average weight loss was 7.7 kg at 8 weeks,

which is no greater than that expected from caloric restriction alone.[6] The

ability of low carbohydrate intake to generate ketones has been touted as a

relative advantage for losing weight. However, this advantage was not confirmed

in a 1-month study comparing ketogenic with nonketogenic hypocaloric diets.[7]

Most comparison studies have evaluated the relative advantages of either a low

carbohydrate or low fat hypocaloric diets; some studies found a slight 1- to

3-kg greater weight loss on a low-carbohydrate diet,[8] [9] [10] [11] others a

slight advantage with a high-carbohydrate diet,[12] but most studies have

observed no statistical advantage of a low-carbohydrate diet.[13] [14] [15] [16]

[17] [18] The preponderance of evidence suggests that as long as caloric intake

remains constant,[19] there is no intrinsic advantage to cutting carbohydrate

intake.[20]

 

Untoward metabolic effects

 

Complications from ketosis

Eucaloric ketogenic diets have been prescribed as part of an antiepileptic

regimen in children with refractory seizure disorders. Children following these

ketogenic diets have higher rates of dehydration, constipation, and kidney

stones. Other reported adverse effects include hyperlipidemia, impaired

neutrophil function, optic neuropathy, osteoporosis, and protein deficiency.[21]

 

Because ketogenic diets effect the central nervous system, it has been suspected

that ketogenic diets may alter cognitive function. In a randomized weight loss

study comparing a ketogenic with a nonketogenic hypocaloric diet, subjects

consuming the ketogenic diet had impairments in higher order mental processing

and flexibility than those following the nonketogenic diet.[7]

 

 

Complications from high saturated fat intake

Despite the beneficial effects of weight loss, diets that promote liberal intake

of high fat meats and dairy products raise cholesterol levels. In a study 24

subjects following the Atkins'-type 4-week induction diet, then 4 weeks

maintenance diet,[6] low-density lipoprotein cholesterol levels increased

significantly from 127 to 151 mg/dl. Similar increases in total cholesterol

(13%) were reported in a study of patients following the Stillman diet.[22]

 

 

Complications from high fat intake

High fat diets increase free fatty acid flux and circulating free fatty acids.

Fasting plasma free fatty acids may have a pro-arrhythmic effect in cardiac

muscle. A number of mechanisms have been suggested including a possible

detergent effect of circulating free fatty acids on cell membranes and direct

effects of acylcarnitine on cellular ion channels and exchangers.

 

 

Complications from exclusion of fruits, vegetables, and grains

Because they exclude fruits, vegetables, and grains, low-carbohydrate,

high-protein diets are deficient in micronutrients. Children consuming

low-carbohydrate ketogenic diets have reduced intakes of calcium, magnesium, and

iron.[21] Two sailors following a low-carbohydrate, high-protein hypocaloric

diet during an extended voyage developed optic neuropathy from thiamine

deficiency.[23] Although vitamin deficiencies can be circumvented by

supplemental multivitamins, even supplemented low-carbohydrate diets will still

be deficient in a growing number of important, biologically active

phytochemicals present in fruits, vegetables, and grains.

 

 

Complications from high-protein intake

Increasing the protein content of a diet significantly increases glomerular

filtration rate.[24] [25] Increases in glomerular filtration rate are likely

explained by increased renal capillary permeability. Unfortunately, this

compensatory response to the greater production of nitrogen is insufficient to

clear protein by-products, and blood urea nitrogen levels increase. High protein

diets significantly lower urinary pH by increasing titratable acid

concentrations.[25] [26] High protein intakes provide a greater uric acid load

to the kidney. Despite increases in urinary uric acid excretion, increases in

serum uric acid are observed.[6] [26]

 

Untoward long-term effects

 

Development of nephrolithiasis

Hypercalciuria is a risk factor for nephrolithiasis. High-protein diets induce

hypercalciuria by several different mechanisms. High-protein diets increase

glomerular filtration rate and decrease renal tubular reabsorption of calcium.

The relation between dietary protein intake and calcium excretion (Table 1) is

clearly linear.[27]

 

 

 

TABLE 1. Graded Effects of High-Protein Diets on Urinary Calcium

Excretion

* Percent calories calculated assuming 70-kg average subject weight,

2,400-calorie diet.

? Significantly different from low-protein diet.

Diet Duration

% Calories from Protein*

No.

Creatinine Clearance (ml/min)

Urinary Calcium Excretion (mg/24 h)

 

Low Medium High Low Medium High

15 d 1%/12%/25% 6 98 105 122 51 99 161

4 d 8%/12%/25% 16 85 95 107 108 129? 196?

15 d 8%/16%/24% 33 168 240? 301?

15 d 8%/16%/24% 9 217 303? 426?

15 d 8%/16%/24% 9 168 240? 301?

 

 

The stone-forming propensity of the hypercalciuria induced by high-protein diets

is aggravated by other changes in urine composition. A high animal protein diet

reduces gastrointestinal alkali absorption, leading to reduced urinary

citrate.[28] Hyperuricemia and hyperuricosuria are also associated with excess

intake of animal protein. Animal protein is a rich source of sulfur-containing

amino acids; amino acids have a greater propensity to lower urinary pH.

 

Adding a carbohydrate restriction to a high-protein diet exacerbates many of

these parameters. Low-carbohydrate intake further reduces urinary pH by inducing

ketosis. Limiting the intake of vegetables and fruits further reduces urinary

citrate by reducing dietary sources of alkali. Thus, high-protein,

low-carbohydrate diets are associated with hypercalciuria, hyperuricosuria, and

hypocitraturia, which can all contribute to renal calculi formation.

 

 

Development of osteoporosis

High-protein, low-carbohydrate diets generate a high acid load, resulting in a

subclinical chronic metabolic acidosis. Metabolic acidosis promotes calcium

mobilization from bone.[29] Osteoclasts and osteoblasts respond to small changes

in pH in cell culture; thus, a small decrease in pH results in a large burst of

bone resorption.

 

The effects of varying dietary protein intakes on bone turnover has been

carefully documented in young women consuming metabolic diets. High-protein

diets increase renal calcium excretion, raised parathyroid hormone levels, and

raise urinary N-telopeptide concentrations. Markers of bone formation (alkaline

phosphatase and osteocalcin) remain steady, suggesting that high-protein diets

increase bone resorption without affecting the rate of bone formation.[27] These

effects may be exaggerated in older persons who tend to have decrements in renal

clearance of acid and higher serum parathyroid hormone concentrations.[29]

 

 

Progression of chronic renal insufficiency

In several small, randomized, controlled dietary trials, dietary protein

restriction retarded the progression of diabetic nephropathy to end-stage renal

disease.[30] High-protein, low-carbohydrate diets have a weak effect at reducing

creatinine clearance over time, and could potentially hasten renal failure in

patients with baseline renal insufficiency.

 

Patients are inherently attracted to the simple, permissive dietary

instructions: eat as much as you want of foods containing fat and protein, but

don't eat foods containing carbohydrate. As promised, almost everyone loses

weight during the first week. Low-carbohydrate diets cause a greater initial

weight loss from a physiologic diuresis accompanying the obligate loss of

glycogen stores and renal clearance of ketone bodies. Once glycogen stores have

been liberated, and a new steady state for total body sodium has been achieved,

these diets hold no greater promise for weight loss than any other caloric

restricted diet. High-fat, low-carbohydrate diets can be harmful. The diet plan

is deficient in micronutrients. Consuming ad libitum fatty meats raises total

and low-density lipoprotein cholesterol levels. High-protein, low-carbohydrate

intakes create a subclinical metabolic acidosis, and increase blood urea

nitrogen and uric acid levels. Resultant urine acidification, hyperuricosuria,

and hypercalciuria increase urine lithogenicity. Trying to convince a devotee to

stop the diet uncovers yet another deleterious effect; ketogenic diets impair

higher order cognitive function. High-protein, low-carbohydrate diets have

untoward clinical consequences for patients with coronary artery disease,

including progression of diabetic nephropathy, exacerbation of gouty diathesis,

increases in circulating free fatty acids, and increases in low-density

lipoprotein cholesterol levels. High-protein, lowcarbohydrate diets are not

superior weight-losing diets and should not be recommended.

 

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