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Systematic Review Question(s): What is the relationship between low

carbohydrate diets and health?

Methods
A preliminary literature search was conducted to identify studies published since 2000 that examined the
relationship between consumption of a low carbohydrate diet (<45% energy from carbohydrate) and a
variety of health outcomes, including body weight, cardiovascular disease, type 2 diabetes, cancer
(breast, colorectal, lung, prostate), bone health, neurological-pyschological illnesses, and congenital
abnormalities.

A summary of the included studies is provided below. The main reasons that studies were excluded
during screening was for having a sample size of <30 subjects per study arm, a drop-out rate >20%, and
for not examining a diet that was low-carbohdyrate (<45% carbohydrate).

Summary of Literature Search Results

Overall, it appears that there is limited evidence available to address the relationship between low-
carbohydrate diets (<45% energy from carbohydrate) and health, particularly evidence derived from U.S.-
based populations. The most evidence available focused on low-carbohydrate diets and body weight,
though the studies tended to be relatively short in duration and were conducted in small populations with
limited generalizability to the U.S. population. The following is a summary of the studies identified for each
outcome of interest, including the study designs, country in which the study was conducted, and the
specific outcomes examined.

Cardiovascular Disease
• Seven articles examined the relationship between low-carbohydrate diets and cardiovascular disease,
including 3 intervention studies and 4 prospective cohort studies.
• The intervention studies were conducted in the US, UK, and Spain, and tested the effects of diets with
differing macronutrient content on various cardiovascular disease outcomes:
o Two studies examined blood pressure
o One study examined blood lipids (LDL, HDL, and total cholesterol) and triglycerides
• The four prospective cohort studies examined the relationship between carbohydrate content of the diet
and cardiovascular disease mortality, and were conducted in Sweden and Japan.

Type 2 Diabetes
• No articles were identified that examined the relationship between low-carbohydrate diets and type 2
diabetes.

Body Weight
• Twenty-eight articles examined the relationship between low-carbohydrate diets and body weight,
including 26 randomized controlled trials, 1 non-randomized controlled trial, and 1 prospective cohort
study.
o The intervention studies were conducted in the US (10), Australia (4), Denmark (2), Israel (2),
New Zealand (2), Canada, Germany, Iran, the Netherlands, Norway, Spain, and in multiple
European sites. The prospective cohort study was conducted in the US.
o One study was conducted in children, and 27 studies were conducted in adults.

• The 2010 DGAC examine the relationship between macronutrient proportion and various body weight
outcomes. Below is a brief summary of the questions they addressed, along with the conclusion
statements and grades:
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o What is the optimal proportion of dietary fat, carbohydrate, and protein to lose weight if
overweight or obese? (DGAC 2010)
 There is strong and consistent evidence that when calorie intake is controlled, macronutrient
proportion of the diet is not related to losing weight. Grade: Strong
o What is the optimal proportion of dietary fat, carbohydrate and protein to avoid regain in weight-
reduced persons? (DGAC 2010)
 A moderate body of evidence provides no data to suggest that any one macronutrient is more
effective than any other for avoiding weight re-gain in weight reduced persons. Grade:
Moderate
o Are low-carbohydrate (less than 45%) hypocaloric diets safe and effective for long-term (more
than six months) weight loss or maintenance? (DGAC 2010)
 A moderate body of evidence demonstrates that diets with less than 45% of calories as
carbohydrates are not more successful for long-term weight loss (12 months). There is also
some evidence that they may be less safe. In shorter-term studies, low-calorie, high-protein
diets may result in greater weight loss, but these differences are not sustained over time.
Grade: Moderate
o Are high-protein (>35%) hypocaloric diets safe and effective for long term (more than six months)
weight loss or maintenance? (DGAC 2010)
 A moderate amount of evidence demonstrates that intake of dietary patterns with less than
45% calories from carbohydrate or more than 35% calories from protein are not more
effective than other diets for weight loss or weight maintenance, are difficult to maintain over
the long term, and may be less safe. Grade: Moderate

Cancer (Breast, Colorectal, Lung, Prostate)

Breast cancer
• Two prospective cohort studies examined the relationship between low-carbohydrate diets and risk of
breast cancer. The studies were conducted in the US and Sweden.

Colorectal cancer
• One prospective cohort study conducted in Sweden examined the relationship between low-
carbohydrate diets and risk of colorectal cancer.

Lung cancer
• One prospective cohort study conducted in Sweden examined the relationship between low-
carbohydrate diets and risk of lung cancer (respiratory cancer).

Prostate cancer
• Two prospective cohort studies conducted in Sweden examined the relationship between low-
carbohydrate diets and risk of prostate cancer.

Bone Health
• No articles were identified that examined the relationship between low-carbohydrate diets and bone
health.

Neurological-Psychological Illnesses
• Two prospective cohort studies examined the relationship between low-carbohydrate diets and
neurological-psychological illness. The studies were conducted in the US and Sweden.
o One study examined incident mild cognitive impairment and dementia.
o One study examined cognitive dysfunction, as indicated by Alzheimer's disease (AD), all-type
dementia, and all-type cognitive impairment.

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Congenital Abnormalities
• No articles were identified that examined the relationship between low-carbohydrate diets and
congenital abnormalities.

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5. Nilsson LM,Winkvist A,Eliasson M,Jansson JH,Hallmans G,Johansson I,Lindahl B,Lenner P,Van

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Type 2 Diabetes
No articles identified.

Body Weight
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2. Archer WR,Lamarche B,St-Pierre AC,Mauger JF,Deriaz O,Landry N,Corneau L,Despres JP,Bergeron

J,Couture P,Bergeron N. High carbohydrate and high monounsaturated fatty acid diets similarly affect
LDL electrophoretic characteristics in men who are losing weight. J Nutr. 2003;133(10):3124-9.
PMID:14519795. http://www.ncbi.nlm.nih.gov/pubmed/14519795

3. Azadbakht L,Izadi V,Surkan PJ,Esmaillzadeh A. Effect of a High Protein Weight Loss Diet on Weight,
High-Sensitivity C-Reactive Protein, and Cardiovascular Risk among Overweight and Obese Women:
A Parallel Clinical Trial. Int J Endocrinol. 2013;2013(#number#):971724. PMID:23986778.
http://www.ncbi.nlm.nih.gov/pubmed/23986778

4. Bazzano LA,Hu T,Reynolds K,Yao L,Bunol C,Liu Y,Chen CS,Klag MJ,Whelton PK,He J. Effects of
low-carbohydrate and low-fat diets: a randomized trial. Ann Intern Med. 2014;161(5):309-18.
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5. Bray GA,Smith SR,DeJonge L,de Souza R,Rood J,Champagne CM,Laranjo N,Carey V,Obarzanek
E,Loria CM,Anton SD,Ryan DH,Greenway FL,Williamson D,Sacks FM. Effect of diet composition on
energy expenditure during weight loss: the POUNDS LOST Study. Int J Obes (Lond).
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6. de Jonge L,Bray GA,Smith SR,Ryan DH,de Souza RJ,Loria CM,Champagne CM,Williamson

DA,Sacks FM. Effect of diet composition and weight loss on resting energy expenditure in the
POUNDS LOST study. Obesity (Silver Spring). 2012;20(12):2384-9. PMID:22627912.
http://www.ncbi.nlm.nih.gov/pubmed/22627912

7. de Luis DA,Aller R,Izaola O,Gonzalez Sagrado M,Bellioo D,Conde R. Effects of a low-fat versus a
low-carbohydrate diet on adipocytokines in obese adults. Horm Res. 2007;67(6):296-300.
PMID:17284923. http://www.ncbi.nlm.nih.gov/pubmed/17284923

8. Duckworth LC,Gately PJ,Radley D,Cooke CB,King RF,Hill AJ. RCT of a high-protein diet on hunger
motivation and weight-loss in obese children: an extension and replication. Obesity (Silver Spring).
2009;17(9):1808-10. PMID:19343014. http://www.ncbi.nlm.nih.gov/pubmed/19343014

9. Due A,Larsen TM,Mu H,Hermansen K,Stender S,Astrup A. Comparison of 3 ad libitum diets for
weight-loss maintenance, risk of cardiovascular disease, and diabetes: a 6-mo randomized,
controlled trial. Am J Clin Nutr. 2008;88(5):1232-41. PMID:18996857.
http://www.ncbi.nlm.nih.gov/pubmed/18996857

10. Ebbeling CB,Leidig MM,Feldman HA,Lovesky MM,Ludwig DS. Effects of a low-glycemic load vs low-
fat diet in obese young adults: a randomized trial. Jama. 2007;297(19):2092-102. PMID:17507345.
http://www.ncbi.nlm.nih.gov/pubmed/17507345

11. Eckel RH,Hernandez TL,Bell ML,Weil KM,Shepard TY,Grunwald GK,Sharp TA,Francis CC,Hill JO.
Carbohydrate balance predicts weight and fat gain in adults. Am J Clin Nutr. 2006;83(4):803-8.
PMID:16600931. http://www.ncbi.nlm.nih.gov/pubmed/16600931

12. Frisch S,Zittermann A,Berthold HK,Gotting C,Kuhn J,Kleesiek K,Stehle P,Kortke H. A randomized
controlled trial on the efficacy of carbohydrate-reduced or fat-reduced diets in patients attending a
telemedically guided weight loss program. Cardiovasc Diabetol. 2009;8(#number#):36.
PMID:19615091. http://www.ncbi.nlm.nih.gov/pubmed/19615091

13. Gardner CD,Kiazand A,Alhassan S,Kim S,Stafford RS,Balise RR,Kraemer HC,King AC. Comparison
of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among
overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. Jama.
2007;297(9):969-77. PMID:17341711. http://www.ncbi.nlm.nih.gov/pubmed/17341711

14. Greenberg I,Stampfer MJ,Schwarzfuchs D,Shai I. Adherence and success in long-term weight loss
diets: the dietary intervention randomized controlled trial (DIRECT). J Am Coll Nutr. 2009;28(2):159-
68. PMID:19828901. http://www.ncbi.nlm.nih.gov/pubmed/19828901

15. Heggen E,Klemsdal TO,Haugen F,Holme I,Tonstad S. Effect of a low-fat versus a low-gycemic-load
diet on inflammatory biomarker and adipokine concentrations. Metab Syndr Relat Disord.
2012;10(6):437-42. PMID:22889406. http://www.ncbi.nlm.nih.gov/pubmed/22889406

16. Keogh JB,Brinkworth GD,Noakes M,Belobrajdic DP,Buckley JD,Clifton PM. Effects of weight loss
from a very-low-carbohydrate diet on endothelial function and markers of cardiovascular disease risk
in subjects with abdominal obesity. Am J Clin Nutr. 2008;87(3):567-76. PMID:18326593.
http://www.ncbi.nlm.nih.gov/pubmed/18326593

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17. Krauss RM,Blanche PJ,Rawlings RS,Fernstrom HS,Williams PT. Separate effects of reduced
carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr. 2006;83(5):1025-
31; quiz 1205. PMID:16685042. http://www.ncbi.nlm.nih.gov/pubmed/16685042

18. Kreider RB,Rasmussen C,Kerksick CM,Wilborn C,Taylor Lt,Campbell B,Magrans-Courtney T,Fogt

D,Ferreira M,Li R,Galbreath M,Iosia M,Cooke M,Serra M,Gutierrez J,Byrd M,Kresta JY,Simbo
S,Oliver J,Greenwood M. A carbohydrate-restricted diet during resistance training promotes more
favorable changes in body composition and markers of health in obese women with and without
insulin resistance. Phys Sportsmed. 2011;39(2):27-40. PMID:21673483.
http://www.ncbi.nlm.nih.gov/pubmed/21673483

19. McAuley KA,Hopkins CM,Smith KJ,McLay RT,Williams SM,Taylor RW,Mann JI. Comparison of high-
fat and high-protein diets with a high-carbohydrate diet in insulin-resistant obese women.
Diabetologia. 2005;48(1):8-16. PMID:15616799. http://www.ncbi.nlm.nih.gov/pubmed/15616799

20. McMillan-Price J,Petocz P,Atkinson F,O'Neill K,Samman S,Steinbeck K,Caterson I,Brand-Miller J.

Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in
overweight and obese young adults: a randomized controlled trial. Arch Intern Med.
2006;166(14):1466-75. PMID:16864756. http://www.ncbi.nlm.nih.gov/pubmed/16864756

21. Noakes M,Keogh JB,Foster PR,Clifton PM. 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(6):1298-306.
PMID:15941879. http://www.ncbi.nlm.nih.gov/pubmed/15941879

22. Phelan S,Wyatt H,Nassery S,Dibello J,Fava JL,Hill JO,Wing RR. Three-year weight change in
successful weight losers who lost weight on a low-carbohydrate diet. Obesity (Silver Spring).
2007;15(10):2470-7. PMID:17925473. http://www.ncbi.nlm.nih.gov/pubmed/17925473

23. Sacks FM,Bray GA,Carey VJ,Smith SR,Ryan DH,Anton SD,McManus K,Champagne CM,Bishop
LM,Laranjo N,Leboff MS,Rood JC,de Jonge L,Greenway FL,Loria CM,Obarzanek E,Williamson DA.
Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl
J Med. 2009;360(9):859-73. PMID:19246357. http://www.ncbi.nlm.nih.gov/pubmed/19246357

24. Shai I,Schwarzfuchs D,Henkin Y,Shahar DR,Witkow S,Greenberg I,Golan R,Fraser D,Bolotin A,Vardi
H,Tangi-Rozental O,Zuk-Ramot R,Sarusi B,Brickner D,Schwartz Z,Sheiner E,Marko R,Katorza
E,Thiery J,Fiedler GM,Bluher M,Stumvoll M,Stampfer MJ. Weight loss with a low-carbohydrate,
Mediterranean, or low-fat diet. N Engl J Med. 2008;359(3):229-41. PMID:18635428.
http://www.ncbi.nlm.nih.gov/pubmed/18635428

25. Soenen S,Bonomi AG,Lemmens SG,Scholte J,Thijssen MA,van Berkum F,Westerterp-Plantenga MS.
Relatively high-protein or 'low-carb' energy-restricted diets for body weight loss and body weight
maintenance?. Physiol Behav. 2012;107(3):374-80. PMID:22935440.
http://www.ncbi.nlm.nih.gov/pubmed/22935440

26. Tay J,Brinkworth GD,Noakes M,Keogh J,Clifton PM. Metabolic effects of weight loss on a very-low-
carbohydrate diet compared with an isocaloric high-carbohydrate diet in abdominally obese subjects.
J Am Coll Cardiol. 2008;51(1):59-67. PMID:18174038.
http://www.ncbi.nlm.nih.gov/pubmed/18174038

27. Te Morenga LA,Levers MT,Williams SM,Brown RC,Mann J. Comparison of high protein and high fiber
weight-loss diets in women with risk factors for the metabolic syndrome: a randomized trial. Nutr J.
2011;10(#number#):40. PMID:21524314. http://www.ncbi.nlm.nih.gov/pubmed/21524314

28. Tierney AC,McMonagle J,Shaw DI,Gulseth HL,Helal O,Saris WH,Paniagua JA,Golabek-Leszczynska

I,Defoort C,Williams CM,Karsltrom B,Vessby B,Dembinska-Kiec A,Lopez-Miranda J,Blaak EE,Drevon
CA,Gibney MJ,Lovegrove JA,Roche HM. Effects of dietary fat modification on insulin sensitivity and

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on other risk factors of the metabolic syndrome--LIPGENE: a European randomized dietary

intervention study. Int J Obes (Lond). 2011;35(6):800-9. PMID:20938439.
http://www.ncbi.nlm.nih.gov/pubmed/20938439

Cancer (Breast, Colorectal, Lung, Prostate)

Breast cancer
1. Fung TT,Hu FB,Hankinson SE,Willett WC,Holmes MD. Low-carbohydrate diets, dietary approaches
to stop hypertension-style diets, and the risk of postmenopausal breast cancer. Am J Epidemiol.
2011;174(6):652-60. PMID:21832271.

2. Nilsson LM,Winkvist A,Johansson I,Lindahl B,Hallmans G,Lenner P,Van Guelpen B. Low-

carbohydrate, high-protein diet score and risk of incident cancer; a prospective cohort study. Nutr J.
2013;12(1):58. PMID:23651548.

Colorectal cancer
1. Nilsson LM,Winkvist A,Johansson I,Lindahl B,Hallmans G,Lenner P,Van Guelpen B. Low-
carbohydrate, high-protein diet score and risk of incident cancer; a prospective cohort study. Nutr J.
2013;12(1):58. PMID:23651548.

Lung cancer
1. Nilsson LM,Winkvist A,Johansson I,Lindahl B,Hallmans G,Lenner P,Van Guelpen B. Low-
carbohydrate, high-protein diet score and risk of incident cancer; a prospective cohort study. Nutr J.
2013;12(1):58. PMID:23651548.

Prostate cancer
1. Ax E,Garmo H,Grundmark B,Bill-Axelson A,Holmberg L,Becker W,Zethelius B,Cederholm T,Sjogren
P. Dietary patterns and prostate cancer risk: report from the population based ULSAM cohort study of
Swedish men. Nutr Cancer. 2014;66(1):77-87. PMID:24325263.

2. Nilsson LM,Winkvist A,Johansson I,Lindahl B,Hallmans G,Lenner P,Van Guelpen B. Low-

carbohydrate, high-protein diet score and risk of incident cancer; a prospective cohort study. Nutr J.
2013;12(1):58. PMID:23651548.

Bone Health
No articles identified.

Neurological-Psychological Illnesses
1. Olsson E,Karlstrom B,Kilander L,Byberg L,Cederholm T,Sjogren P. Dietary Patterns and Cognitive
Dysfunction in a 12-Year Follow-up Study of 70 Year Old Men. J Alzheimers Dis. 2014.
PMID:25062901. http://www.ncbi.nlm.nih.gov/pubmed/25062901

2. Roberts RO,Roberts LA,Geda YE,Cha RH,Pankratz VS,O'Connor HM,Knopman DS,Petersen RC.

Relative intake of macronutrients impacts risk of mild cognitive impairment or dementia. J Alzheimers
Dis. 2012;32(2):329-39. PMID:22810099. http://www.ncbi.nlm.nih.gov/pubmed/22810099

Congenital Abnormalities
No articles identified

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