Fat Loss Biology
Intermittent Fasting Clock

Wouldn’t it be nice to see what the real science is behind intermittent fasting so you can cut through all the marketing hype about it? A recent article in the Wall Street Journal sort of helps, even though it was a bit shallow. Here is how to find some truths on the topic, based on scientific research. And it doesn’t cost anything!


Intermittent Fasting News

The article in question was titled, ‘What Science Says About Mini-Fasts for Weight Loss’. It followed some typical journalistic protocol by citing comments by a couple of researchers and by one or two regular folks who have some personal experience. The biggest missing part of the article was the usual comment by an additional expert about how we really don’t know enough about it to do any good.

The article was definitely slanted favorably toward mini-fast, which is fine. And it did provide a couple of flighty references to research. The nice thing about such references is that, if sufficient detail is included about them, they can be dug up in the journals where they were published. Anyone who is super-interested in the details and what may have been overlooked or misconstrued in the media about the research can find out by accessing the research articles at the U.S. Government’s public medical database, PubMed.

All you have to do is know how to look. This post is about how to get started, with comments on what to make of the research behind intermittent fasting as far as your own health decisions go.

Intermittent Fasting Research

First off, it is important to narrow down the topic. If you simply enter a search for ‘intermittent fasting’ (in quotes), you will get a list of more than 160 published articles that entail this topic in some way. An easier and more efficient way to find useful research is to search on the name of a researcher who has published studies on the subject of interest.

The WSJ article cited a bit of research by a ‘Krista Varady’ as one of its sources. She is an Assistant Professor in the Dept. of Kinesiology and Nutrition at the University of Illinois at Chicago. A little more digging about her will reach her faculty website there (Varady, Krista at UIC). It provides an impressive overview of her overall research, a few selected publications, her grant funding sources, and her educational background.

Prof. Varady is clearly a young scientist of note who has done some research on intermittent fasting. Now let’s see what her work tells us.

To get a more complete picture from the PubMed database, just plug in varady-ka in the search box. (This is how you do an author search; names do not have to be capitalized.) At this time the result lists 43 publications with KA Varady as an author. (There are reasons why an author shows up first, last, or in between in a multi-author publication. This entails a fascinating subject concerning how faculty get credit for their work.)

Not all of Prof. Varady’s publications are directly about intermittent fasting. If you are looking over the complete search results, you can almost tell by the titles which ones are. The neat thing is that you can expand the list to include published abstracts, which gives you a better idea of the topic of each article. An added bonus is that some of the articles are available in full without charge.

Just in case you want to see the entire list, with published abstracts, and are a little intimidated by the PubMed site, here is a download of all of Prof. Varady’s articles with abstracts (in text format): Varady References.

If you are looking for some quick answers to basic questions, you will see some trends in the results of selected articles by Prof. Varady. For the public at large, these questions might include: Is intermittent fasting worthwhile for me? If it is, what can I expect from it? And how do I go about doing it most effectively?

Now let’s see what we can find in Prof. Varady’s publications that might provide some answers.

The Most Informative Articles

The following might be the articles that best answer the practical questions that you have about intermittent fasting. The abbreviated format, for simplicity, in the following is, 1) the journal citation data (author list, article title, journal name publication year and volume); and, 2) the single line summary or conclusion from the abstract that is most informative. You may also see bracketed terms added in where necessary for explaining abbreviations.

The highlighted text accompanying any article is included to provide additional perspective not directly stated in the article itself. This is mostly important for cutting through some of the scientific jargon.

Note that the list starts with the most recent publications and goes backwards in time. On occasion you can see how an earlier study asks questions and lays the groundwork for later studies.

Varady KA, Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Haus JM, Hoddy KK, Calvo Y. Alternate day fasting for weight loss in normal weight and overweight subjects: a randomized controlled trial. Nutr J. 2013 Nov 12(1):146. [Epub ahead of print]

CONCLUSION: These findings suggest that ADF [alternate day fasting] is effective for weight loss and cardioprotection in normal weight and overweight adults, though further research implementing larger sample sizes is required before solid conclusion can be reached.

Aha! This is great news! Weight loss AND heart benefits for heart health.

Bhutani S, Klempel MC, Kroeger CM, Aggour E, Calvo Y, Trepanowski JF, Hoddy KK, Varady KA. Effect of exercising while fasting on eating behaviors and food intake. J Int Soc Sports Nutr. 2013 10(1):50. [Epub ahead of print]

CONCLUSION: These findings suggest that endurance exercise is an excellent adjunct therapy to ADF, as it leads to positive behavioral changes that may contribute to long-term steady weight loss.

Most folks are not going to do endurance exercise. It would be wonderful to see how high-intensity interval training would compare, since research in HIIT shows how much easier and more effective it is for endurance fitness that actual endurance training.

Klempel MC, Kroeger CM, Varady KA. Alternate day fasting increases LDL particle size independently of dietary fat content in obese humans. Eur J Clin Nutr. 2013 67(7):783-5.

Thus, our results suggest that the ADF-HF [alternate day fasting – high fat] diet is equally as effective as the ADF-LF [alternate day fasting – low fat] diet in improving LDL particle size and distribution.

LDL levels alone are now known to be almost irrelevant. The key health indicator is the size of the LDL particles. The smaller the more dangerous. ADF improves the proportion of larger vs. smaller LDL particles. The amount of dietary fat, low or high, makes no difference.

Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA. Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans. Obesity (Silver Spring). 2013 21(7):1370-9.

CONCLUSIONS: These findings suggest that the combination produces superior changes in body weight, body composition, and lipid indicators of heart disease risk, when compared to individual treatments.

Klempel MC, Kroeger CM, Bhutani S, Trepanowski JF, Varady KA. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women. Nutr J. 2012 11:98.

CONCLUSION: These findings suggest that IF [intermittent fasting] combined with CR [caloric restriction] and liquid meals is an effective strategy to help obese women lose weight and lower CHD risk.

Kroeger CM, Klempel MC, Bhutani S, Trepanowski JF, Tangney CC, Varady KA. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations. Nutr Metab (Lond). 2012 9(1):98.

CONCLUSION: These findings suggest that IFCR with a liquid diet favorably modulates visceral fat and adipokines in a way that may confer protection against CHD.

Klempel MC, Kroeger CM, Varady KA. Alternate day fasting (ADF) with a high-fat diet produces similar weight loss and cardio-protection as ADF with a low-fat diet. Metabolism. 2013 Jan;62(1):137-43.

CONCLUSION: These findings suggest that an ADF-HF diet is equally as effective as an ADF-LF diet in helping obese subjects lose weight and improve CHD risk factors.

Varady KA, Bhutani S, Klempel MC, Kroeger CM. Comparison of effects of diet versus exercise weight loss regimens on LDL and HDL particle size in obese adults. Lipids Health Dis. 2011 10:119.

CONCLUSION: These results indicate that dietary restriction increases LDL particle size, while endurance training augments HDL particle size, with minimal weight loss. None of these interventions concomitantly increased both LDL and HDL particle size, however.

Varady KA. Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss? Obes Rev. 2011 12(7):593-601.

These findings suggest that these diets are equally as effective in decreasing body weight and fat mass, although intermittent CR may be more effective for the retention of lean mass.

Varady KA, Bhutani S, Klempel MC, Lamarche B. Improvements in LDL particle size and distribution by short-term alternate day modified fasting in obese adults. Br J Nutr. 2011 105(4):580-3.

These findings suggest that ADMF is an effective diet strategy for increasing LDL particle size and decreasing the proportion of small, dense LDL particles in obese adults.

Varady KA, Bhutani S, Church EC, Klempel MC. Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults. Am J Clin Nutr. 2009 90(5):1138-43.

CONCLUSION: These findings suggest that ADF is a viable diet option to help obese individuals lose weight and decrease CAD [coronary artery disease] risk.

Varady KA, Hudak CS, Hellerstein MK. Modified alternate-day fasting and cardioprotection: relation to adipose tissue dynamics and dietary fat intake. Metabolism. 2009 58(6):803-11.

In summary, modified ADF regimens alter adipose tissue physiology (ie, body fat distribution, TG metabolism, and adipokines) in a way that may protect against coronary heart disease. These beneficial effects were noted over a wide range of fat intake, suggesting that ADF may be protective even in the presence of HF diets.

Varady KA, Allister CA, Roohk DJ, Hellerstein MK. Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restriction. J Nutr Biochem. 2010 21(3):188-95.

These findings indicate that ADF (both modified and true) produces similar beneficial modulations in body fat distribution and adiponectin levels as daily CR.

Varady KA, Roohk DJ, Bruss M, Hellerstein MK. Alternate-day fasting reduces global cell proliferation rates independently of dietary fat content in mice. Nutrition. 2009 25(4):486-91.

CONCLUSION: These findings indicate that ADF has an antiproliferative effect over a wide range of fat intakes, which may enhance adherence to ADF in humans.

‘Antiproliferative effect’ is the fancy way that scientists refer to inhibition of cellular reproduction that may be associated with tumors, either cancerous or non-cancerous. An antiproliferative effect is accepted as a health benefit.

Varady KA, Roohk DJ, McEvoy-Hein BK, Gaylinn BD, Thorner MO, Hellerstein MK. Modified alternate-day fasting regimens reduce cell proliferation rates to a similar extent as daily calorie restriction in mice. FASEB J. 2008 22(6):2090-6.

In summary, modified ADF, allowing the consumption of 15% of energy needs on the restricted intake day, decreases global cell proliferation similarly as true ADF and daily CR without reducing body weight.

Varady KA, Roohk DJ, Loe YC, McEvoy-Hein BK, Hellerstein MK. Effects of modified alternate-day fasting regimens on adipocyte size, triglyceride metabolism, and plasma adiponectin levels in mice. J Lipid Res. 2007 48(10):2212-9.

In summary, modified ADF (ADF-50%) and complete ADF (ADF-100%) regimens modulate adipocyte function, despite there being no change in body weight or adipose tissue weight in the former group.

Varady KA, Roohk DJ, Hellerstein MK. Dose effects of modified alternate-day fasting regimens on in vivo cell proliferation and plasma insulin-like growth factor-1 in mice. J Appl Physiol (1985). 2007 Aug;103(2):547-51.

These findings confirm the beneficial effects of ADF-100% on cancer risk by decreasing cell proliferation and IGF-1 levels and suggest that modified ADF regimens comprising 25-50% CR on the fast day do not replicate these effects.

This article makes a crucial point about the comparative ineffectiveness of reducing calories by only 25-50% on fasting days.

Varady KA, Lamarche B, Santosa S, Demonty I, Charest A, Jones PJ. Effect of weight loss resulting from a combined low-fat diet/exercise regimen on low-density lipoprotein particle size and distribution in obese women. Metabolism. 2006 55(10):1302-7.

In conclusion, these findings suggest that weight loss, resulting from a low-fat diet/exercise program, has only a minimal effect on LDL particle size and distribution.

This 2006 article is particularly interesting in light of more recent research (cited above) that shows an improvement in LDL particle sizes distribution with alternate day fasting. Weight loss alone doesn’t do the trick.


Of course, this is just a thumbnail sketch of the topic of intermittent fasting through the research of one scientist. What this sketch shows is helpful, though. Alternate day fasting or alternate day caloric restriction of at least 75% (i,e., consuming 25% of daily calories on alternate days) are obviously of benefit in several ways. Weight loss is just one of them.

The actual approach to fasting can be done differently. Every other day with caloric restriction, every other day with 100% fasting, or just constant caloric restriction (meaning eliminating at least one-third of of what you normally eat, every meal, every day) are just some of the possibilities.

The main advantage of intermittent fasting vs. constant caloric restriction is that people stick with it better. Who wants to be hungry all the time? Constant hunger is one of the factors that undermines CR.

Who can tolerate and adapt to fasting every other day, or 2-3 times per week, or at least just once per week? Especially if the fasting is only partial – such as 75% reduction of food consumption? At lot more people, it turns out.

Much of the research on the health benefits of intermittent fasting, including weight/fat management, are based on a pattern of 100% fasting for 18-24 hours at a time. Based on my personal experience, this is the easiest and most effective way to gain the benefits of fasting.

Beneficial effects from this pattern are also age-related. Effects diminish as we age. Older folks must fast more often to get the same benefits as younger folks. Two to three times per week (some recommend four!) are more helpful for us ‘mature’ adults (50s, 60s, 70s, and beyond).

If is seems to you that not all the answers you wanted are clear, well, that is the way scientific research goes. It is slow and methodical and provides only the tiniest progress on a subject in any one publication. Sometimes you just have to do the experiments on yourself to see what works and what doesn’t.

All the best with YOUR intermittent fasting,

Dr. D

4 Comments so far »

  1. by Ed


    I have read a lot about Resveratral the past few years and have been taking it regularly. My cholesterol level is high, including the LDL. Some of the abstracts I’ve read about Resveratral seem to indicate it helps to prevent the LDL from sticking to artery walls. Do you have an opinion on this?

  2. by Dr. Dennis Clark


    Hi, Ed…You ask very good questions. Yes, resveratrol can be helpful in its role as an antioxidant. Many related phytochemicals among the flavonoids can do the same. This puts a premium on getting lots of colored veggies into your diet. The way the protect is not necessarily to stop LDL from sticking to artery walls directly. Antioxidants counteract oxidative damage to artery walls that enable all kinds of things to stick to them, not just LDL. More importantly, antioxidants help to keep the small particle LDL, the really dangerous type, from oxidizing. The combination of damaged artery walls, too much small particle LDL, and oxidized LDL is the toxic mix that antioxidants help with. Resveratrol is one of the better ones.

    All the best,

  3. by smmus.es


    The upsides: Some people find it easier to have bulletproof willpower for just part of the time than to eat more moderately all of the time. Several small studies have found lower blood sugar, blood pressure and cholesterol levels with fasting.

  4. by Dr. Dennis Clark


    Good point, smmus.es. In fact an interview with Ray Wolford (maybe the “father of calorie restriction), he and his daughter said they were hungry all the time. This doesn’t appeal to most people, including me.

    All the best,

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