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Jan 23, 2004 10:04 PST

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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

---

 

Weight-losing diets appeal to the growing population of overweight

Americans.Fad diets promise rapid weight loss, easy weight loss,

limited restrictions onportion 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

 

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.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.

 

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 " (water-loss).

---

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 " .

 

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

weightloss.

 

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 lone.[6]

 

The bility of low carbohydrate intake to generate ketones has been

touted as a relative avantage for losing weight. However, this

advantage was not confirmed in a 1-month study comparing ketogenic

with nonketogenic hypocaloric diets.

 

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, others a slight advantage with a high-carbohydrate diet,[12]

but most studies have observed no statistical advantage of a

low-carbohydrate diet.

 

The preponderance of evidence suggests that as

long as caloric intake remains constant, there is no intrinsic

advantage to cutting carbohydrate intake.

--

 

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.

 

 

Because ketogenic diets " affect " 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

---

 

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.

 

--

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 apossible

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.

 

Two sailors following a low-carbohydrate, high-protein hypocaloric

diet during an extended

voyage developed " optic neuropathy " from thiamine deficiency.

 

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.

 

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.

 

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.

---

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.

 

 

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.

 

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 (kidney) 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.

 

References

 

1. Anonymous. A critique of low-carbohydrate ketogenic weight

reduction

regimens. A review of Dr. Atkins' diet revolution. JAMA

1973;224:1415-1419.

2. Johnstone AM. Effect of overfeeding macronutrients on day-to-day

food intake

in man. Eur J Clin Nutr 1996;50:418-30. Abstract

3. Yudkin J. The treatment of obesity by the high fat diet. Lancet

1960;2:939-41.

4. Kolanowski J. On the mechanisms of fasting natriuresis and of

carbohydrate-induced sodium retention. Diabetes Metab 1977;3:131-43.

5. Yang MU, Van Itallie TB. Composition of weight lost during short-

term weight

reduction. Metabolic responses of obese subjects to starvation and

low-calorie

ketogenic and nonketogenic diets. J Clin Invest 1976;58:722-30.

Abstract

6. LaRosa JC, Fry AG, Muesing R, Rosing DR. Effects of high-protein,

low-carbohydrate dieting on plasma lipoproteins and body weight. J

Am Diet Assoc

1980;77:264-70. Abstract

7. Wing RR, Vazquez J, Ryan C. Cognitive effects of ketogenic weight

reducing

diets. Int J Obes Relat Metab Disord 1995;19:811-6. Abstract

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composition on

metabolic adaptations to hypocaloric nutritioncomparison of high

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and high fat isocaloric diets. Am J Clin Nutr 1977;30:160-70.

Abstract

9. Rabast U, Kasper H, Schonborn J. Obesity and low-carbohydrate

diets-comparative studies. Nutr Metab 1977;21(suppl 1):56-9. Citation

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carbohydrate, protein, and fat content of the diet upon weight loss,

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1990;90:534-40.

Abstract

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12. Rabast U, Vornberger KH, Ehl M. Loss of weight, sodium and water

in obese

persons consuming a high- or low-carbohydrate diet. Ann Nutr Metab

1981;25:341-9. Abstract

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and

low-carbohydrate diets on nitrogen balance during calorie

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subjects. Int J Obes 1982;6:457-62. Citation

14. Piatti PM, Pontiroli AE. Insulin sensitivity and lipid levels in

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15. Rumpler WV, Seale JL. Energy intake restriction and diet

composition effects

on energy expenditure in men. Am J Clin Nutr 1995;53:430-6.

16. Low CC, Grossman EB, Gumbiner B. Potentiation of effects of

weight loss by

monounsaturated fatty acids in obese NIDDM patients. Diabetes

1996;45:569-75.

Abstract

17. Golay A, Allaz AF, Morel Y, de Tonnac N, Tankova S, Reaven G.

Similar weight

loss with low- or high-carbohydrate diets. Am J Clin Nutr

1996;63:174-8.

Abstract

18. Golay A, Eigenheer C, Morel Y, Kujawski P, Lehmann T, de Tonnac

N.

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carbohydrate in ad libitum fat reduced diet for the treatment of

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20. Shah M, Garg A. High fat and high carbohydrate diets and energy

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Diabetes Care 1996;19:1142-52. Abstract

21. Tallian K, Nahata M, Tsao CT. Role of ketogenic diet in children

with

intractable seizures. Ann Pharmacother 1998;32:349-61. Abstract

22. Rickman F, Mitchell N. Changes in serum cholesterol during the

Stillman

diet. JAMA 1974;228:54-8. Citation

23. Hoyt III CS, Billson FA. Low-carbohydrate diet optic neuropathy.

Med J Aust

1977;1:65-6. Abstract

24. Kerstetter JE, O'Brien KO, Insogna KL. Dietary protein affects

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25. Schuette SA. Studies of the mechanism of protein induced

hypercalciuria in

older men and women. J Nutr 1980;110:305-15. Abstract

26. Fellstrom B, Danielson BG, Karlstrom B, Lithell H, Ljunghall S,

Vessby B.

The influence of a high dietary intake of purine-rich animal protein

on urinary

urate excretion and supersaturation in renal stone disease. Clin Sci

1983;64:399-405. Abstract

27. Kerstetter JE, Mitnick ME, Gundberg CM, Caseria DM, Ellison AF,

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Full Text

28. Breslau NA, Brinkley L, Hill KD, Pak CY. Relationship of animal

protein-rich

diet to kidney stone formation and calcium metabolism. J Clin

Endocrinol Metab

1988;66:140-6. Abstract

29. Barzel US, Massey LK. Excess dietary protein can adversely

affect bone. J

Nutr 1998;128:1051-3. Abstract

30. Kasiske BL, lakatua JD, Ma JZ, Louis TA. A meta-analysis of the

effects of

dietary protein restriction on the rate of decline in renal

function. Am J

Kidney Dis 1998;31:954-61. Abstract

 

 

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: mde-@m...

 

Manuscript received January 16, 2000;

revised manuscript received January 6, 2001,

accepted January 6, 2001

PII S0002-9149(01)01586-7

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