Randomized Controlled Trials in Nutrition

This is a collection of high quality research studies in nutrition, about some of the topics we cover on this website.

All of these studies are published in respected, peer-reviewed journals.

A Randomized Controlled Trial is a type of experiment that is considered to be the gold standard for a clinical trial.

Participants in such a study are randomized into two or more groups, where each group gets a different type of treatment.

All of the studies on this page are randomized controlled trials in humans, unless otherwise noted!

Low-Carbohydrate vs. Low-Fat Diets

A low carb diet is based on foods that contain a low amount of carbohydrate. Foods that are high in sugars and starches are replaced with foods that are high in protein and fat.

A low fat diet, is based on foods that contain a low amount of fat, typically under 30% of total calories. Foods like fruits, vegetables and whole grains are emphasized.

The studies below are controlled trials where people are randomized to either a low-carb or a low-fat diet. The outcomes measured are usually body weight and risk factors for disease.

  1. Soenen, et al. Relatively high-protein or “low-carb” energy-restricted diets for body weight loss and body weight maintenance? Physiol Behav. 2012 Oct 10;107(3):374-80.

  2. Krebs NF, et al. Efficacy and safety of a high protein, low carbohydrate diet for weight loss in severely obese adolescents. J Pediatr. 2010 Aug;157(2):252-8.

  3. Hernandez, et al. Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet. Am J Clin Nutr March 2010 vol. 91 no. 3 578-585.

  4. Brinkworth GD, et al. Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. Am J Clin Nutr. 2009 Jul;90(1):23-32.

  5. Volek JS, et al. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids. 2009 Apr;44(4):297-309.

  6. Tay J, et al. 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 Jan 1;51(1):59-67.

  7. Keogh JB, et al. 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 Mar;87(3):567-76.

  8. Shai I, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008 Jul 17;359(3):229-41.

  9. Dyson PA, et al. A low-carbohydrate diet is more effective in reducing body weight than healthy eating in both diabetic and non-diabetic subjects. Diabet Med. 2007 Dec;24(12):1430-5.

  10. Halyburton AK, et al. Low- and high-carbohydrate weight-loss diets have similar effects on mood but not cognitive performance. Am J Clin Nutr. 2007 Sep;86(3):580-7.

  11. Gardner CD, et al. 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 Mar 7;297(9):969-77.

  12. McClernon FJ, et al. The effects of a low-carbohydrate ketogenic diet and a low-fat diet on mood, hunger, and other self-reported symptoms. Obesity (Silver Spring). 2007 Jan;15(1):182-7.

  13. Nickols-Richardson SM, et al. Perceived hunger is lower and weight loss is greater in overweight premenopausal women consuming a low-carbohydrate/high-protein vs high-carbohydrate/low-fat diet. J Am Diet Assoc. 2005 Sep;105(9):1433-7.

  14. Meckling KA, et al. Comparison of a low-fat diet to a low-carbohydrate diet on weight loss, body composition, and risk factors for diabetes and cardiovascular disease in free-living, overweight men and women. J Clin Endocrinol Metab. 2004 Jun;89(6):2717-23.

  15. JS Volek, et al. Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women. Nutr Metab (Lond). 2004; 1: 13.

  16. Yancy WS Jr, et al. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med. 2004 May 18;140(10):769-77.

  17. Aude YW, et al. The national cholesterol education program diet vs a diet lower in carbohydrates and higher in protein and monounsaturated fat: a randomized trial. Arch Intern Med. 2004 Oct 25;164(19):2141-6.

  18. Brehm BJ, et al. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab. 2003 Apr;88(4):1617-23.

  19. Sondike SB, et al. Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents. J Pediatr. 2003 Mar;142(3):253-8.

  20. Samaha FF, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003 May 22;348(21):2074-81.

  21. Foster GD, et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. 2003 May 22;348(21):2082-90.

    22. Low-Carb and Type II Diabetes:

  22. Guldbrand, et al. In type 2 diabetes, randomization to advice to follow a low-carbohydrate diet transiently improves glycaemic control compared with advice to follow a low-fat diet producing a similar weight loss. Diabetologia. 2012 Aug;55(8):2118-27.

  23. Westman EC, et al. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond). 2008 Dec 19;5:36.

  24. Daly ME, et al. Short-term effects of severe dietary carbohydrate-restriction advice in Type 2 diabetes – a randomized controlled trial. Diabet Med. 2006 Jan;23(1):15-20.

Main Results: Low-carb diets usually lead to more weight loss than low-fat diets, even when the low-fat groups are calorie restricted while the low-carb groups are not.

Low-carbohydrate diets also significantly improve major risk factors for diseases like cardiovascular disease and type II diabetes.

Meta-Analyses of Low-Carb Diet Studies

These studies are meta-analyses of randomized controlled trials of low-carbohydrate diets.

  1. Santos F, et al. Systematic review and meta-analysis of clinical trials of the effects of low carbohydrate diets on cardiovascular risk factors. Obesity Reviews, 13: 1048–1066.

  2. Hession M, et al. Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. Obesity Reviews, 10: 36–50.

  3. Westman EC, et al. Low-carbohydrate nutrition and metabolism. Am J Clin Nutr August 2007 86: 2 276-284
Main Results: Same as above. Low-carb diets lead to more weight loss and further improvements in metabolic health compared to the low-fat diet that is usually recommended by nutritionists and governments around the world.

The Paleolithic Diet

Randomized controlled trials of the paleolithic diet (commonly known as the paleo diet or caveman diet).

  1. Jönsson T, et al. Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study. Cardiovascular Diabetology 2009, 8:35.

  2. Lindeberg S, et al. A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease. Diabetologia. 2007 Sep;50(9):1795-807.
Main Results: The paleo diet has favorable effects on body weight and major risk factors. However, the studies available are very small so the results must be taken with a grain of salt.

Vitamin D3 Supplementation

A deficiency in Vitamin D is very common today, especially in countries where there is little sun throughout most of the year.

Vitamin D3 and cancer:

  1. Lappe JM, et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007 Jun;85(6):1586-91.

    2. Vitamin D, fractures and falls:

  2. Meta-analysis: Bischoff-Ferrari HA, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005 May 11;293(18):2257-64.

  3. Trivedi DP, et al. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 2003;326:469.

  4. Broe KE, et al. A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. J Am Geriatr Soc. 2007 Feb;55(2):234-9.

    5. Vitamin D3 and Influenza A Infections:

  5. Urashima M, et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr May 2010.
Main Results: Vitamin D supplementation reduces risk of falls and fractures in the elderly at higher doses. May reduce risk of cancer and respiratory infections.

Is This List Missing Something?

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There is no cherry picking here. All relevant studies are included. If you find something that should be included in this list, post it in the comments below.

10 Comments

  1. Anna says:
    January 3, 2013 at 2:34 pm

    Hello and thank you for this article. I’m wondering have you looked into research on vitamin D3 shortage and supplementation and it’s effects on depression symptoms/clinical depression?

    Reply
    • Kris Gunnars says:
      January 4, 2013 at 12:25 pm

      I haven’t seen much research on it but it wouldn’t surprise me if there was some effect. A Vitamin D deficiency can affect the body in many ways.

      Reply
    • Ron says:
      May 16, 2013 at 5:43 pm

      I recently started supplementing with Vitamin D3 50,000 IU capsules; I had a month or two where I just felt like garbage all the time and had a viral sinus infection that just wouldn’t go away. I performed what is referred to as a Stoss Dose (look it up for more info) and took a capsule every a.m. for three days, though it is sometimes recommended to take two or three depending upon weight. It’s made a huge difference – I feel much better, don’t need as much sleep, and don’t feel low-energy all the time. It is an immune/mood booster, and now I take a capsule every couple weeks to maintain my levels. Highly recommend it, even if only to perform the Stoss Dose.

      Reply
  2. Damon says:
    February 11, 2013 at 8:11 pm

    Do all the studies listed that compare low carb to low fat include body composition in the conclusions? I’ve read several studies that showed that low fat diets will get you more WEIGHT loss, however low carb diets get you more FAT loss. I think it’s an important distinction and you can usually tell if the study didn’t go as the researchers wanted if they did body composition at the beginning but not at the end.

    Reply
  3. Elliot says:
    March 21, 2013 at 11:55 am

    Just thought you might want to know that Dr. Lindeberg did another study comparing a Paleo diet to a Mediterranean diet:
    http://www.ncbi.nlm.nih.gov/pubmed/21118562
    As expected, the Paleo diet won.

    Reply
  4. Luke says:
    March 25, 2013 at 11:56 pm

    Hi Kris,

    What is your take on this article against saturated fat?

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572653/

    Reply
    • Kris Gunnars says:
      March 26, 2013 at 8:51 am

      I’ll have to give it a closer read when I have the time.

      Excess carbs get turned into saturated fats in the liver. On a low-carb diet, the body preferably burns saturated fat for energy, which actually leads to a reduction in the blood.

      A quick glance seems to tell me that the studies are referring to blood levels of saturated fat, not dietary intake per se. It is known that low-carb diets actually reduce blood levels, even though dietary intake may be high.

      Reply
      • Luke says:
        March 26, 2013 at 11:38 am

        Thanks A lot Kris!

        It’s nice to know that there are evidence based people with the right critical thinking skills to turn to when you have questions.

        I love the site and have got so much useful stuff and external links from it. I especially like how easy to follow and straight forward the articles are.

        Keep up the great work and I will keep sharing the site to friends and family.

        Luke

        Reply
  5. Aaron Richoux says:
    May 23, 2013 at 2:01 pm

    I would like to see evidence supporting avoiding artificial sweeteners.

    Reply
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