Is Advil Preventing You From Getting Pregnant?

This month, I’m taking a break from diet to explore another important area in health and wellness: fertility. Any girl who’s ever turned to Google or Pinterest in search of increasing fertility has no doubt encountered hundreds of tips and tricks. As usual, some are reliable and others are based on myth and anecdote.

Eat vegan. Eat Paleo. Eat whole-30. No smoking. No alcohol. Some alcohol. No caffeine. Some caffeine. Prenatal vitamins. Ovulation predictors. Work out more. Work out less. Yoga. Acupuncture. Hypnosis. Basal body temperature. Do it every day. Don’t do it every day. Test for STDs. Get a semen analysis. Test your tubes. Test for endometriosis.

One recommendation in particular caught my attention. I came across a headline saying that NSAIDs (non-steroidal anti-inflammatory drugs) can prevent ovulation. I had never heard about this before and decided to take a deeper look.

NSAIDs are over-the-counter pain medications that work by blocking enzymes that make prostaglandins (which cause swelling and are interpreted as pain). Many people take these medications fairly often for headaches, backaches, joint pain, menstrual cramps, toothaches, other injuries, and even heart disease.

Some common OTC NSAIDs are: Aspirin (Bayer, Excedrin), Ibuprofen (Advil, Motrin, Nuprin), Ketoprofen (Actron, Orudis), and Naproxen (Aleve). Others are available with a prescription.

The Claim: Taking NSAIDs can reduce fertility by preventing ovulation.

Initial Search: A quick Google search came up with the following results:

WebMD: NSAIDs may hinder ovulation and lower levels of the female hormone progesterone. They cite a study by Sami Salman, MD, from the University of Baghdad. This study is available below in the peer-reviewed research section. Essentially, he studied 39 women taking either an NSAID or a placebo for 10 consecutive days, beginning on day 10 of the menstrual cycle. Ovulation was reduced by 75-93% depending on which drug the patients were taking compared to the control group. He stated that progesterone levels also dropped for the experimental groups. After discontinuing treatment, all of the women ovulated normally during their next cycle. Dr. Salman even proposed that these findings could help them develop a new contraceptive.

Medscape: Pharmacist Darrell Hullsz describes how some side effects of NSAIDs are well known including gastrointestinal, cardiovascular, and renal problems as well as problems toward the end of pregnancy. He says that problems with ovulation have been reported for several decades, but that these problems are still not widely known. An enzyme, COX-2, that is active in the ovaries during follicular development, is blocked by NSAIDs. This prevents the follicule from rupturing (egg from being released). Women see all the other signs of ovulation including elevated body temperature and progesterone levels, but the egg is never released. He goes a step further stating that COX-2 inhibitors may also disrupt fertilization, implantation, and establishment of the placenta. He references the study mentioned above by WebMD as well as two other studies listed below in the peer-reviewed section that oppose the claim by suggesting that delayed follicular rupture is unlikely to cause infertility.

Many other popular health news websites also cite Dr. Salman’s study including: ScienceDaily, Daily Mail, Pharmaceutical Journal, Holistic Primary Care, TheraSpecs, and many fertility blogs and centers.

Follow-up Questions:

If NSAIDs really do affect fertility, does timing and dosage matter? Would it be ok to take NSAIDs during your period, but avoid it during the middle and end of your cycle? Is a lower dose safer?

Are there other painkillers that are safer to take when trying to conceive?

Peer reviewed Research:

These are all of the relevant studies I found. Most did not have full text available. I have provided abstracts with the most important findings from each study in bold.



Background: NSAIDs are popular and used as analgesics, antipyretics and anti-inflammatory agents for more than a century. They are sold without a prescription and taken by millions of patients every day all over the world. There has been recent concerns as to their use in females at child bearing age, as many animal studies showed unfavourable effects on ovulation.

Objectives: To study the effects of short term use of NSADs at their conventional dosages on ovulation.

Methods: Thirty nine women at fertile age were chosen as volunteers to take part in this study, they visited the Rheumatology consultation clinic in Baghdad Hospital, suffering from minor backpain and received one of the three test drugs (diclofenac 100mg once daily, naproxen 500mg twice daily & etoricoxib 90mg once daily). Treatment with the above drugs was given for ten days starting at day ten of the onset of the menstrual cycle. A blood sample was taken from each patients for hormonal analysis (progesterone level) together with an ultra sonsography to assess the mean diameter of the dominant follicle. At day twenty the patient came back for another ultra sonography & to give a blood sample for another check for progesterone level. A fourth group served as controls, who received no treatment (control volunteers).

Results: There was significant inhibition of ovulation in patients treated with diclofenac, naproxen & etoricoxib. Diclofenac was the highest inhibitor of ovulation compared to the other two drugs (naproxen & etoricoxib). A significant decrease in progesterone level in all three groups in compared to the control group was found. Functional cysts have been observed in one third of patients by the end of the treatment period with diclofenac, naproxen & etoricoxib due to unruptured follicles these disappeared at the next cycle.

Conclusions: The findings may serve as an alarm of the harmful effects of these drugs on female fertility and be taken into consideration in females planning to have a child. The above results may open the door for looking for an emergency contraceptive safer than those at use.



Ovulation constitutes the central event in ovarian physiology, and ovulatory disfunction is a relevant cause of female infertility. Non-steroidal anti-inflammatory drugs (NSAIDs), widely used due to their analgesic and anti-inflammatory properties, consistently inhibit ovulation in all mammalian species investigated so far, likely due to the inhibition of cyclooxygenase 2 (COX-2), the inducible isoform of COX, that is the rate-limiting enzyme in prostaglandin (PG) synthesis. COX-2 inhibition has major effects on ovulation, fertilization and implantation, and NSAID therapy is likely implicated in human infertility and could be an important, frequently overlooked, cause of ovulatory disfunction in women. Although there is compelling evidence for a role of PGs in ovulation, the molecular targets and the precise role of these compounds in the ovulatory process are not fully understood. Morphological studies from rats treated with indomethacin (INDO), a potent inhibitor of PG synthesis, provide evidence on the actions of NSAIDs in ovulation, as well as on the possible roles of PGs in the ovulatory process. Cycling rats treated with INDO during the preovulatory period show abnormal ovulation, due to disruption of the spatial targeting of follicle rupture at the apex. Noticeably, gonadotropin-primed immature rats (widely used as a model for the study of ovulation) show age-dependent ovulatory defects similar to those of cycling rats treated with INDO. These data suggest that NSAID treatment disrupts physiological mechanisms underlying spatial targeting of follicle rupture at the apex, which are not fully established in very young rats. We summarize herein the ovulatory defects after pharmacologic COX-2 inhibition, and discuss the possible mechanisms underlying the anti-ovulatory actions of NSAIDs.



Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed to women of child-bearing age. Three case series highlight the possibility of a link between NSAIDs and reversible infertility. The pharmacological target of NSAIDs is cyclo-oxygenase (COX), which catalyses the first rate-limiting step in the production of prostaglandins. COX-2, one of two isoenzymes, is active in the ovaries during follicular development. Its inhibition is thought to cause luteinised unruptured follicle (LUF) syndrome, an anovulatory condition characterised by clinical signs of ovulation but in the absence of follicular rupture and ovum release. The evidence linking regular NSAID use to reversible LUF syndrome comes from animal studies and three clinical studies. COX-2-deficient mice have severely compromised ovulation in the presence of apparently normal follicular development. Experimental administration of prostaglandins induced ovulation in rabbits and this was blocked by the administration of indomethacin. The three clinical studies demonstrated the induction of delayed follicular rupture or LUF in previously ovulating women by the administration of NSAIDs. A link can therefore be identified between NSAID use and reversible female infertility and NSAID withdrawal should be considered prior to or concurrent with fertility investigations.



BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors may interfere with ovulation and the rupture of the follicle, causing reversible infertility.

METHOD: Literature review.

RESULTS: Reversible infertility is shown both in animal and human studies of these drugs. As determined by ultrasound, the drugs may delay or inhibit ovulation. These findings are also confirmed by a few randomized controlled studies showing an increase in time from the luteinizing hormone surge to rupture of the follicle and an increased size of the unruptured follicle. Most of the hormone analyses show values in accordance with the ovulation/menstrual cycle. Also, two epidemiological studies have shown an association between NSAID use and spontaneous abortion. These studies have methodological weaknesses and their findings have to be elucidated in future studies.

INTERPRETATION: Women with fertility problems should avoid not only the selective cyclooxygenase-2 inhibitors, but also the traditional NSAIDs. However, women with rheumatic disease responding well to therapy should consult their physicians before stopping treatment. Reduced dose of a NSAID and temporary stop of drug treatment early in the menstrual cycle, or alternative drug treatment, may be a solution. NSAIDs should not be used in the last eight weeks of pregnancy.

  • 5. Reversible ovulatory failure associated with the development of luteinized unruptured follicles in women with inflammatory arthritis taking non-steroidal anti-inflammatory drugs. (1996)



The case histories of three young women with ankylosing spondylitis, rheumatoid arthritis and a seronegative inflammatory polyarthritis undergoing investigations for infertility are presented. In each, non-steroidal anti-inflammatory drug (NSAID) therapy was associated with the recurrent development of luteinized unruptured ovarian follicles and normal ovulation following drug withdrawal. It is suggested that NSAID therapy may be an important and frequently overlooked cause of anovulation and infertility.


Abstract (1) There have been isolated reports of reversible female infertility linked to NSAIDs. The likely mechanism is ovulatory failure due to non rupture of mature follicles. (2) If a woman who presents with infertility is found to be taking a NSAID, the role of the drug should be considered before launching costly, invasive investigations or starting medically assisted reproduction.



OBJECTIVE: To highlight the possible association between infertility and treatment with long-term non-steroidal anti-inflammatory drug (NSAIDs). NSAIDs act mainly through the inhibition of cyclooxygenase, the enzyme that catalyses the synthesis of prostaglandins, which are essential mediators of ovulation, implantation and placentation of the conceptus.

METHODS: Case reports of four women suffering from severe arthritis, on long-term NSAIDs and undergoing extensive investigation and treatment for infertility.

RESULTS: During the last 2 yr, four out of five women with severe arthritis and difficulty conceiving were counselled to stop NSAIDs, and they successfully conceived shortly after the withdrawal of NSAIDs.

CONCLUSION: NSAIDs, used largely for the treatment of rheumatological conditions, may be responsible for some cases of infertility.


Abstract: Non-steroidal anti-inflammatory drugs are widely used in the treatment of inflammatory joint diseases. Many patients suffering from these disorders are young women during their childbearing years. We report three cases of infertility where the cause may have been NSAID-induced ‘luteinized unruptured follicle’ syndrome. This phenomenon is well recognized in obstetric circles, and we would like to bring it to the attention of rheumatologists since it is not documented in the rheumatological literature.



STUDY QUESTION: Does use of commonly used over-the-counter (OTC) pain medication affect reproductive hormones and ovulatory function in premenopausal women?

SUMMARY ANSWER: Few associations were found between analgesic medication use and reproductive hormones, but use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for potential confounders.

WHAT IS KNOWN ALREADY: Analgesic medications are the most commonly used OTC drugs among women, but their potential effects on reproductive function are unclear.

STUDY DESIGN, SIZE, DURATION: The BioCycle Study was a prospective, observational cohort study (2005-2007) which followed 259 women for one (n = 9) or two (n = 250) menstrual cycles.

PARTICIPANTS, SETTING, METHODS: Two hundred and fifty-nine healthy, premenopausal women not using hormonal contraception and living in western New York state. Study visits took place at the University at Buffalo.

MAIN RESULTS AND THE ROLE OF CHANCE: During study participation, 68% (n = 175) of women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33% acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for age, race, body mass index, perceived stress level and alcohol consumption (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for potential confounding by indication by adjusting for ‘healthy’ cycle indicators such as amount of blood loss and menstrual pain during the preceding menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, -1.6-32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no associations were observed with estradiol, LH or FSH.

LIMITATIONS, REASONS FOR CAUTION: Self-report daily diaries are not validated measures of medication usage, which could lead to some classification error of medication use. We were also limited in our evaluation of aspirin and naproxen which were used by few women.

WIDER IMPLICATIONS OF THE FINDINGS: The observed associations between follicular phase analgesic use and higher progesterone and a lower probability of sporadic anovulation indicate that OTC pain medication use is likely not harmful to reproduction function, and certain medications possibly improve ovulatory function.



OBJECTIVE: To assess the effect of ibuprofen, a nonspecific inhibitor of prostaglandin synthesis, on ovulation.

DESIGN: Prospective, randomized, double-blind, placebo-controlled cross-over study.

SETTING: University Medical Center.

PATIENT(S): Twelve normally cycling women between ages 20 and 40.

INTERVENTION(S): Subjects were randomized to either oral ibuprofen (800 mg) or placebo three times per day, beginning when the maximum diameter of the leading follicle reached 16 mm by ultrasound, and continuing for 10 days total. The second cycle was a washout period, and in the third cycle, the subjects were crossed over to the alternate regimen from the first cycle. The probability of delayed follicular collapse was determined using the binomial distribution, and changes in P levels were compared using the paired t test.

MAIN OUTCOME MEASURE(S): Urinary LH surge, follicular collapse by serial transvaginal ultrasonography, and serum midluteal P levels.

RESULT(S): Eleven of 12 subjects detected an LH surge with both ibuprofen and placebo. Five of 11 women demonstrated a >or=2-day increase in time interval from detection of the LH surge to follicular collapse, and 3 of those 5 had been randomized to ibuprofen. This represents a 27% (3 of 11; 95% confidence limits: 1%, 53%) rate of delay for follicular collapse for ibuprofen. There was no difference in average midluteal P levels for ibuprofen or placebo.

CONCLUSION(S): If ibuprofen inhibits follicular collapse, this effect is seen in a small group of study subjects, and this information should be clinically reassuring to patients who take nonsteroidal anti-inflammatory drugs. Serum midluteal P levels were unaffected by administration of ibuprofen.

What we know and don’t know

The research I found doesn’t give us a very definitive answer. 8 out of the 10 studies or reviews point to a strong association between NSAIDs and ovulation problems. However, in most of these studies, subjects took high doses for an extended period of time (at least 10 consecutive days). Some of them used NSAIDs that are unpopular or unavailable in the US. 1 out of the 10 studies suggests a weak association between NSAIDs and ovulation problems and 1 out of the 10 studies actually suggests that NSAIDs can improve ovulation.

Here is a table to help make the findings more clear

Study number Number/description of subjects Type of study Outcome with NSAIDs
1 39 women Control trial (non-random) poor
2 rats Unsure, review? poor
3 3 women Case studies poor
4 unsure Review poor
5 3 women Case studies poor
6 “isolated reports” Review poor
7 4 women Case studies poor
8 3 women Case studies poor
9 259 women Control trial (non-random) good
10 12 women Randomized control trial Poor in a small group


The majority of studies reporting poor outcomes are case studies involving 3 or 4 women. They may even be citing the same 3 or 4 women in multiple articles. It is difficult to know details (such as exactly which medications the women were taking and for how long) from the abstracts. However, we do know that in study 1 most of the women were taking medications not available in the US. In study 9 however, the women were mostly using Advil. This might make findings from study 9 more relevant. Study 10 is the highest quality in terms of research design, but with only 12 subjects, the results may not be reliable.

The possible mechanism responsible for ovulation problems while using NSAIDs is well described and seems plausible. According to this research, it has been observed in all mammals. However, studies involving mice and rats may still not be relevant to humans.


Overall, it seems like there is some good evidence to suggest that taking NSAIDs regularly can cause problems with ovulation. Unfortunately, there is still some controversy. I wasn’t able to find any good information on lower doses or the importance of timing, but subjects in these studies all took the medications around the time of ovulation.

I was also unable to find any information on good alternatives. Study 9, which claimed painkillers do not cause ovulation problems, didn’t separate out NSAIDs and acetaminophen. A quick Google search suggests that acetaminophen (like Tylenol) is safe during pregnancy, but may reduce estrogen and luteinizing hormones in the body. This could affect fertility.  I have yet to look deeper into this claim.


My recommendation would be for anyone who has had unexplained infertility for more than 3 months to stop taking NSAIDs and use Tylenol for mild/occasional pain relief (unless your doctor doesn’t think this would be safe). Fertility treatments are often very expensive and might be avoided by simply switching pain medication.

Is Paleo Best for Avoiding Metabolic Syndrome?

The Paleolithic (Paleo) diet has become incredibly popular over the past decade. I even tried it myself for about a year. The enthusiastic supporters and wild claims surrounding this diet are similar to what we see in the vegan diet. Just in case you’ve been living under a rock (or have never entered a CrossFit gym), here is a brief description of the Paleo diet.

The idea is to eat things that would have been available to cave men, before agriculture. This would include meat, seafood, vegetables, fruits, eggs, nuts and seeds. It would exclude grains, legumes, dairy, refined sugars and oils, and all processed foods. Some versions of the diet include potatoes, whole unpasteurized dairy, saturated fats, organ meats, salt, red wine, and very dark chocolate, while others do not.

The Claim

The best way to achieve optimal nutrition and prevent/reverse markers of metabolic syndrome is to eat a Paleo diet consisting of meat, seafood, vegetables, fruits, eggs, nuts, and seeds.

Initial Google Search

Dr. Loren Cordain is considered to be the founder of the “Paleo movement”. He has authored many peer reviewed articles and written several popular books over the past few decades promoting the diet. Other popular Paleo experts include: Robb Wolf (author of The Paleo Solution and credited for popularizing the Paleo diet through the CrossFit community), Mark Sission (author of The Primal Blueprint and website Mark’s Daily Apple), Gary Taubes (author of Good Calories, Bad Calories and Why We Get Fat), Dave Asprey (of Bulletproof Coffee), David Perlmutter (author of Wheat Belly), Melissa Hartwig (of Whole30), and Diane Sanfilippo (author of Practical Paleo).

These and other supporters of the diet say you can eat Paleo foods until you’re full without counting calories and you’ll lose weight, build muscle, and reduce or eliminate markers of metabolic syndrome. They also postulate that many humans are gluten and lactose intolerant. They think eating gluten/grains causes leaky gut and inflammation while dairy products cause allergies, digestive problems, inflammation and autoimmune diseases. They say that with the Paleo diet, the body learns to fuel itself with fat more efficiently and that fat is a better source of energy because it keeps you feeling full longer and prevents energy crashes. Some make even more extreme claims such as that variations of the diet cure autism, autoimmune conditions, and mental illness.

For the purpose of this blog, I will focus on the more traditional Paleo diet which focuses on lean meats, fish, vegetables, fruits, eggs, nuts and seeds; and the claim that eating this way will reduce or prevent metabolic syndrome.

Follow-up Questions

Does the Paleo diet work better than the Vegan diet for weight loss, diabetes, and heart disease?

Are there some variations of the diet that are better than others?

Peer Reviewed Research

Inclusion criteria: clinical trial or review of multiple clinical trials that compare the Paleo diet to another “healthy” control diet. Outcomes must measure markers of metabolic syndrome.

1. Metabolic and physiologic effects from consuming a hunter-gatherer (Paleolithic)-type diet in type 2 diabetes. (2015)

Interpretation: Researchers studied 24 patients with type 2 diabetes. 14 ate a Paleo diet and 10 ate the American Diabetes Association (ADA) diet for 14 days. Both groups had improved metabolic profiles. The Paleo group did better in terms of glucose control and cholesterol.

2.  Favourable effects of consuming a Palaeolithic-type diet on characteristics of the metabolic syndrome: a randomized controlled pilot-study. (2014)

Interpretation: Researchers studied 34 people with at least two characteristics of metabolic syndrome. 18 were assigned to the Paleo group and 14 to the healthy reference diet. 32 people completed the study for 2 weeks. The Paleo group had lower blood pressure, lower total cholesterol, lower triglycerides, and higher HDL than the reference group. No changes were observed for intestinal permeability, inflammation, and salivary cortisol.

3. Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis. (2015)

Interpretation: 4 randomized control trials with a total of 159 participants were reviewed to determine whether a Paleo diet improved metabolic syndrome better than a typical healthy diet. The diets were tested for between 1 week and 3 months. Overall, the Paleo diet improved waist circumference, blood pressure, triglycerides, HDL cholesterol and fasting blood pressure (all measures) better than the typical healthy diet.

4. Cardiovascular, Metabolic Effects and Dietary Composition of Ad-Libitum Paleolithic vs. Australian Guide to Healthy Eating Diets: A 4-Week Randomised Trial. (2016)

Interpretation: 39 healthy women were studied. 22 ate a Paleo diet and 17 ate the recommended Australian healthy diet for 4 weeks. There were no differences in cardiovascular or metabolic markers between the groups at the end of the study.

5. Paleolithic nutrition improves plasma lipid concentrations of hypercholesterolemic adults to a greater extent than traditional heart-healthy dietary recommendations. (2015)

Interpretation: 20 adults with poor cholesterol profiles were studied. They ate an ADA heart healthy diet for 4 months and then a Paleo diet for 4 months. The Paleo diet resulted in lowered total cholesterol, LDL and triglycerides and raised HDL better than the traditional heart healthy diet.

6. Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study. (2009)

Interpretation: 13 patients with type 2 diabetes were studied. They ate a Paleo diet for 3 months and then the standard recommended diabetes diet for 3 months. The Paleo diet showed better outcomes than the diabetes diet in: blood glucose, triacylglycerol, diastolic blood pressure, weight, BMI, waist circumference, and HDL (all measures).

What We Know and Don’t Know

These studies certainly have their limitations. They have few participants and they study changes over short durations. However, the findings are very consistent. For people with markers of metabolic syndrome, the Paleo diet works better than the recommended healthy diet to improve their condition.

Interestingly, we found the same results with the Vegan diet. It seems that both the Paleo diet AND the Vegan diet are better choices than the ADA diet (commonly recommended healthy diet) to control metabolic syndrome. This finding led me to wonder what exactly the ADA diet consists of.

Their website recommends meals that consist of non-starchy vegetables on half your plate and lean meats and whole grains on the other half. They encourage consumption of beans, dark leafy greens, citrus fruits, berries, sweet potatoes, nuts, fish, low fat milk, and yogurt. They discourage consumption of saturated fats, foods high in cholesterol, alcohol, refined grains, and sugar. In short, the ADA diet is the perfect combination of everything included in the Vegan and Paleo diets with the addition of low fat dairy.

This leaves us with another whole list of questions. Is dairy the culprit for metabolic disease? Are there studies directly comparing Paleo and Vegan diets? Is the success of these diets simply reflecting that people lose more weight and improve their health by cutting out more things from their diets? Should some people cut everything from their diets except for the foods represented by both the Vegan AND Paleo diets?

There was one study from the group above that had different results from the rest. Study number 4 was the only one that found no significant differences between participants who ate a Paleo diet and participants who ate the standard healthy diet. This study was also the only one to use healthy participants rather than people with metabolic syndrome. Additionally, the study only used women while the other studies included both men and women (although a few were primarily women). This study may suggest that different populations benefit differently from the diets.

Conclusions and Applications

After completing this research, I am more curious than ever to start investigating dairy. I’d like to see whether the ADA diet without dairy works better than the ADA diet with dairy. I’d also like to see how the ADA diet without dairy would compare to the Vegan and Paleo diets. I’m not sure what I’ll find in the research since these questions are pretty specific.

Also, I’d like more information on which diets might be best for specific populations. I’m a young healthy woman who likes to lift weights. I may not need to be eating the same way as an older overweight, sedentary man. Or, maybe I do.

For now, I won’t be making any changes. Eat food. Mostly plants. Not too much.

Please share your comments and insights!

Can Common Foods Stop Cancer?

Hippocrates said it first, “Let food be thy medicine”. People have been trying to heal disease with food for thousands of years. Several prominent doctors have claimed that food can even heal cancer. Today I am going to explore one of these claims.

Internal medicine doctor, William Li, gave a viral TED Talk in 2012 describing how he believes food can prevent and even help cure many kinds of cancer. A reader provided me with the link to the talk below and asked for my thoughts.

In order to understand his hypothesis, a little bit of background info on a process called angiogenesis is needed. Here is the description from the National Cancer Institute:

“What is angiogenesis?

Angiogenesis is the formation of new blood vessels. This process involves the migration, growth, and differentiation of endothelial cells, which line the inside wall of blood vessels.

The process of angiogenesis is controlled by chemical signals in the body. These signals can stimulate both the repair of damaged blood vessels and the formation of new blood vessels. Other chemical signals, called angiogenesis inhibitors, interfere with blood vessel formation. Normally, the stimulating and inhibiting effects of these chemical signals are balanced so that blood vessels form only when and where they are needed.

Why is angiogenesis important in cancer?

Angiogenesis plays a critical role in the growth and spread of cancer. A blood supply is necessary for tumors to grow beyond a few millimeters in size. Tumors can cause this blood supply to form by giving off chemical signals that stimulate angiogenesis. Tumors can also stimulate nearby normal cells to produce angiogenesis signaling molecules. The resulting new blood vessels “feed” growing tumors with oxygen and nutrients, allowing the cancer cells to invade nearby tissue, to move throughout the body, and to form new colonies of cancer cells, called metastases.

Because tumors cannot grow beyond a certain size or spread without a blood supply, scientists are trying to find ways to block tumor angiogenesis. They are studying natural and synthetic angiogenesis inhibitors, also called antiangiogenic agents, with the idea that these molecules will prevent or slow the growth of cancer.”

There are many FDA approved drugs that treat cancer by preventing or slowing angiogenesis. Dr. Li promotes these drugs. However, he also makes the claim that many foods work just as well or even better than these drugs at inhibiting angiogenesis.

The Claim

Certain foods can inhibit angiogenesis just as well as or better than drugs to treat cancer patients.

Initial Search

After spending several hours googling things like “cancer diet” and “angiogenesis food”, I kept coming up with results leading me back to Dr. Li’s TED Talk. I also came across several websites and foundations represented by Dr. Li including: Eat to Beat, The Angiogenesis Foundation, Alternative Daily, Forks Over Knives, Food Revolution, Collective Evolution, and everyone’s favorite doctor, Dr. Oz.

Interestingly, not one mainstream reputable source mentioned his hypothesis and I was unable to find other doctors in his line of work. Could it be a conspiracy? Big Pharma? Or…….MONSANTO??? Kidding. But really, he seems to be the only one out there peddling this stuff.

Some of his associations provide links to articles by other professionals. However, you have to register to get access to them and many of the authors don’t have doctorates or even any credentials at all.

Several more reputable sources including: MD Anderson, the American Institute of Cancer Research, the World Cancer Research Fund, and WebMD do list foods that can help lower your risk of cancer. However, they do not discuss angiogenesis. I can’t tell whether it’s because the topic is too scientific or because they help prevent cancer through another mechanism or because they just don’t know how the foods help. None of these sources claim that foods can cure cancer or that foods work as well as or better than drugs for prevention and/or treatment. It’s worth noting that many of the foods are similar to those Dr. Li recommends. All of the food lists are heavy on fruits, veggies, legumes and spices. Some include coffees, teas, nuts and even yogurt and sea foods.

Follow-up Questions

What is the quality of the research to support this claim? Are we going to find a bunch of retrospective observational studies that rely on people to remember what they ate over long periods of time?

Do any animal foods also have anti-angiogenic properties?

Do any studies compare outcomes of cancer patients who treated with diet to those who treated with anti-angiogenic drugs?

Reader Comments (see link above to Dr. Li’s TED Talk via Forks Over Knives)

Peer Reviewed Research

1.Tumor Angiogenesis as a Target for Dietary Cancer Prevention (2012)

This is the only peer reviewed article I found directly linking diet to angiogenesis and cancer treatment. Dr. Li from the TED Talk is the first author. It is not a clinical trial, but a review of how specific micronutrients in specific plant foods promote anti-angiogenesis or otherwise inhibit cancer.

First he presents a list of “angiogenic factors” that have been discovered. He then lists “endogenous inhibitors of angiogenesis” that suppress cancer growth. He then describes how genes work to control when new blood vessels are formed. He states that small cancers are common once people reach about 40-50 years of age and that the inhibitors of angiogenesis prevent these cancers from growing too much and becoming dangerous.

Li goes on to describe how some cancers progress to hyperplasia, dysplasia, and then invasive carcinoma by recruiting surrounding blood vessels and enabling new vessels to form. New blood vessels are able to form “by the production and release of one or more angiogenic growth factors…”. He describes how cancers grow and metastasize from there.

Dr. Li discusses current angiogenic therapies that have been proposed and that are in use today. He stresses early treatment before new blood vessels are able to start forming.

Finally, he lists antiangiogenic factors in common foods. For each food, he cites research that supports how they might be preventing cancer in mice, in vitro (test tube), or in human observational epidemiologic or prospective cohort studies. He provides links to all of the studies cited. The factors he describes include:

Green tea catechins, genistein (found in soy beans), resveratrol (found in mulberries, peanuts, grapes, and grape products), lycopene (found in tomatoes, watermelon, and papaya), omega-3 polyunsaturated fatty acids (found in salmon, herring, mackerel, anchovies, sardines and trout), glucosinolates, isothiocynates and indole-3-carbinol (found in cruciferous vegetables such as cabbage, broccoli, cauliflower, collard greens, mustard greens, radishes, brussel sprouts, bok choy, and kale), flavonoids and quercetin (found in many fruits and vegetables), anthocyanins (pigments in berries and grapes), proanthocyanidins (found in cacao and some fruits and vegetables), ellagitannins (found in fruits, vegetables and nuts), manaquinone (vitamin K2 found in dark leafy vegetables and cheese), curcumin (turmeric), beta-cryptoxanthin (found in brightly colored foods).

In the discussion section, Dr. Li does state some of the flaws in the types of studies he reviewed. No human controlled experimental trials have been done. However, he still trusts overall that foods with antiangiogenic factors will help prevent cancer. Interestingly, his paper does not make the claim that these foods work as good as or better than cancer treatments that are already on the market. Instead, he suggests that these foods should be used to help prevent cancer rather than to treat. The paper also never makes bold claims that eating these foods will prevent cancer; only that they may lower one’s chances. Most of the studies he cited showed modest reductions in specific forms of cancer paired with study designs that are known to have high rates of error.

Many other studies address how certain diets can impact cancer. However, I did not find anything other than Dr. Li’s article that claims that the diets are working by inhibiting the growth of new blood vessels. Here are a few reviews, meta-analyses, and one randomized trial I found related to the general question of how diets may cause or help prevent cancer.

2. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women’s Healthy Eating and Living (WHEL) randomized trial. (2007)

CONCLUSION: Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period.

3. Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: a systematic review and meta-analysis. (2014)

CONCLUSIONS: Caloric restriction and ketogenic diet are effective against cancer in animal experiments while the role of intermittent fasting is doubtful and still needs exploration. More clinical experiments are needed and more suitable patterns for humans should be investigated.

4. Vegetarian diets, low-meat diets and health: a review. (2012)

RESULTS: Both vegetarian diets and prudent diets allowing small amounts of red meat are associated with reduced risk of diseases, particularly CHD and type 2 diabetes. There is limited evidence of an association between vegetarian diets and cancer prevention. Evidence linking red meat intake, particularly processed meat, and increased risk of CHD, cancer and type 2 diabetes is convincing and provides indirect support for consumption of a plant-based diet.

5. Diet and cancer: risk factors and epidemiological evidence. (2014)

CONCLUSIONS: There is a direct relationship between unhealthy diet and lifestyle with the increase of tumor development and cancer risk. For this reason, a good nutritional status based on a balanced diet constitutes one of the main preventive factors from tumors. However the mixed results from epidemiologic studies hinder to get unequivocal and consistent evidence about the interaction between diet and cancer risk. More epidemiological studies will be needed in the future to clarify this issue.

6. Diet and Colorectal Cancer Risk in Asia–a Systematic Review.

ABSTRACT SELECTION: We found that red meats, processed meats, preserved foods, saturated/animal fats, cholesterol, high sugar foods, spicy foods, tubers or refined carbohydrates have been found by most studies to have a positive association with colorectal cancer risk. Inversely, calcium/dairy foods, vitamin D, general vegetable/fruit/fiber consumption, cruciferous vegetables, soy bean/soy products, selenium, vitamins C,E and B12, lycophene, alpha-carotene, beta-carotene, folic acid and many other vitamins and minerals play a protective role against colorectal cancer risk. Associations of fish and seafood consumption with colorectal cancer risk are still inconclusive due to many varying findings, and require further more detailed studies to pinpoint the actual correlation. There is either a positive or no association for total meat consumption or white meats, however their influence is not as strong as with red and processed meats.

7. Nutrition and cancer. (2015) translated from Spanish

RESULTS: Fruits and vegetables are the foods that can prevent from cancer disease, soya and fishes also have demonstrated as preventive from some types of malignancies. Clear factors causing cancer are red meat and processed meat, dairy products and alcohol. The protective roles of vitamins, antioxidants and micronutrients still have to be deeply investigated. Obesity is a clear risk factor for cancer, calorie reduction has been proposed as a factor that has protective properties in laboratory studies, but this has to be demonstrated in a clinical scenario.

8. Meat, dairy, and cancer. (2014)

ABSTRACT: In 2007 the World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) report judged that the evidence for an association between red and processed meat consumption and colorectal cancer was convincing. In addition, the effect of other animal products on cancer risk has been studied, and the WCRF/AICR report concluded that milk probably decreases the risk of colorectal cancer but diets high in calcium probably increase the risk of prostate cancer, whereas there was limited evidence for an association between milk and bladder cancer and insufficient evidence for other cancers. There are several potential mechanisms relating meat to cancer, including heterocyclic amines, polycyclic aromatic hydrocarbons, N-nitroso compounds, and heme iron. Although the evidence in favor of a link between red and processed meat and colorectal cancer is convincing, the relations with other cancers are unclear. In this review, we summarize cohort studies conducted by the National Cancer Institute on meat and dairy intake in relation to cancer since the 2007 WCRF/AICR report. We also report the findings of meta-analyses published since 2007.

9. Dairy products and cancer. (2011)

ABSTRACT SELECTION: Based on a systematic review of the epidemiologic literature, the World Cancer Research Fund and American Institute for Cancer Research report concluded there was a probable association between milk intake and lower risk of colorectal cancer, a probable association between diets high in calcium and increased risk of prostate cancer, and limited evidence of an association between milk intake and lower risk of bladder cancer. For other cancers, the evidence was mixed or lacking.

10. Adherence to Mediterranean diet and risk of cancer: an updated systematic review and meta-analysis of observational studies. (2015)

ABSTRACT SELECTION: The aim of the present systematic review and meta-analysis of observational studies was to gain further insight into the effects of adherence to Mediterranean Diet (MD) on overall cancer mortality, incidence of different types of cancer, and cancer mortality risk in cancer survivors. An overall population of 1,784,404 subjects was included in the present update. The highest adherence score to an MD was significantly associated with a lower risk of all-cause cancer mortality, colorectal cancer, breast cancer, gastric cancer, prostate cancer, liver cancer, head and neck cancer, pancreatic cancer, and respiratory cancer. No significant association could be observed for esophageal/ovarian/endometrial/and bladder cancer, respectively. Among cancer survivors, the association between the adherence to the highest MD category and risk of cancer mortality, and cancer recurrence was not statistically significant. The updated meta-analyses confirm a prominent and consistent inverse association provided by adherence to an MD in relation to cancer mortality and risk of several cancer types.

11. Mediterranean diet and cancer: epidemiological evidence and mechanism of selected aspects. (2013)

DISCUSSION: The most recent pooled analyses of epidemiological studies supported strongly the hypothesis that the Mediterranean diet may play a role in preventing several types of cancers, especially those of digestive tract, whereas contrasting results were reported for hormone-dependent cancers. Specific aspects of the Mediterranean diet such as high fruit and vegetables and low red processed meat intake may explain such protective effects. Moreover, evidence regarding olive oil and whole grains increase the beneficial effects of such dietary pattern against cancer.

12. Nutrition and prostate cancer: an overview. (2014)

ABSTRACT SELECTION: Obesity and metabolic syndrome are important risk factors for prostate cancer and their management is key. The amount and type of fats consumed are also clearly related to prostate cancer risk. Saturated fats and trans fats are identified as having a negative impact. Nutraceuticals and supplements, particularly antioxidants, polyphenols and soy have evidence for benefit for prevention of prostate cancer and progression of the disease.

13. Ketogenic Diet and Cancer-a Perspective. (2016)

ABSTRACT SELECTION: Exercise or severe restriction of caloric intake is not always advisable for patients, in particular those suffering from cancer. The ketogenic diet (KD), characterized by high fat, moderate protein and very low carbohydrate composition can evoke a physiological state similar to that triggered by exercise or fasting. These attributes of KD prompted its possible use in treatment of a number of metabolic diseases, including several types of malignancies. Although results from clinical studies employing KD in the treatment of cancer are still limited, the results obtained from animal models are encouraging and show that KD presents a viable option as an adjunct therapy for cancer.

14. The role of dietary factors in prevention and progression of breast cancer. (2014)

RESULTS: Consumption of well-done red meat appears to be associated with increased risk of BC, whereas fish may be protective. Total cholesterol, triglyceride levels and glycaemic load should be monitored and controlled in at risk populations because they may be associated with increased risk of BC, although the exact mechanisms involved are not clear. Alcohol intake should be minimized since it is a risk factor for BC. High intake of polyphenol/phyto-oestrogen -rich food (i.e. flavonoids, soya products), as well as fibres, fruits and vegetables, may have potential protective effects against BC occurrence but the results might vary according to hormonal status. Vitamin D supplements appear protective against BC development and similarly other vitamins and oligo-elements might decrease BC risk, although further large prospective studies are required.

15. Dietary intake and ovarian cancer risk: a systematic review. (2014)

ABSTRACT SELECTION: Higher risk for ovarian cancer was shown for total, animal, and dairy fat (five of nine studies), as well as total nitrate and possibly total vitamin C. No associations were demonstrated for red meat, fiber, vitamin A, vitamin E, β-carotene, or folate. Vegetables were associated with lower risk in one of three studies; fruit showed no association, although risk estimates were all greater than 1.0. Isoflavones and flavonoids were associated with modestly lower risk in two studies and tea intake was associated with lower risk in one of two studies. This review suggests that no specific dietary factors are consistently associated with ovarian cancer risk.

What we know and don’t know:

After the research, we can see that angiogenesis is a necessary process for cancers to grow and become dangerous. We know there are FDA approved drugs to help slow this process. We also know that people who eat a lot of fruits, vegetables, fish, soy, and tea tend to have lower chances of developing most types of cancer than people who drink a lot of alcohol, eat a lot of red and processed meat, eat a lot of trans and saturated fat, and eat foods cooked at high temperatures. There is quite a bit of data to support these general ideas, but few randomized control trials. That means it may be hard to assign cause and effect and the studies may have other various flaws making them less reliable.

Research does not directly support that eating certain properties of plant foods can prevent cancer from establishing a blood supply. However, the research does not directly deny that this is happening. I wasn’t able to find any studies to directly test this hypothesis. No studies were found that compare treating patients with medication to treating patients with diet.

Even if plants are helping to protect people from cancer by way of antiangiogenic properties, it is highly unlikely that plant foods could replace medications. Dr. Li himself doesn’t even suggest this in his own paper. Additionally, Dr. Li’s research supports consumption of certain animal products such as fish, which is conveniently overlooked when presented by vegan groups.

Another common theme throughout the research in the relationship between cancer and diet is simply that eating less can help. Several studies show that reducing calories lowers the chance of developing cancer and that being overweight is a huge cancer risk factor. Some studies also show that a ketogenic diet can prevent and even help treat cancer. In fact, I was able to find more support for ketogenic diets as a cancer treatment than for vegan or nearly vegan diets.

Conclusions and applications:

What should we do with this information? Here’s my list of ideas based on my research:


  • Eat lots of fruits and vegetables every day
  • Eat fish several times a week
  • Soy products are probably good for you, although this is another hot topic
  • Avoid processed meat
  • Eat less red meat and opt for cuts that don’t need to be well done
  • Avoid processed foods, trans fats and sugar
  • Avoid alcohol
  • Maintain a healthy weight
  • If you already have cancer, traditional treatments work better than a plant-based diet, although a ketogenic diet may be helpful.

Should I go Vegan?

Every few years, Netflix stirs the pot with another vegan “documentary”. First it was Food Inc. and Forks Over Knives, then Cowspiracy, and, most recently, What the Health. I’m sure there have been others. These films can be pretty convincing and surely do tempt some people to try veganism for themselves. They do a great job of presenting peer reviewed studies to support their claims. They also show remarkable recoveries from chronic disease.

However, as I’m sure you suspect, they use some pretty sneaky tactics to overstate their claims. They usually cherry pick their studies while ignoring everything that might conflict with their agenda. They report relative rather than absolute risks. They interview doctors who have personal biases. They malign research and medical agencies that refuse to change their policies based on cherry-picked evidence. They try to convince people that correlation is causation. And sometimes, they even lie outright.

Many bloggers and YouTubers have already “debunked” a lot of the points in these films. My purpose in this blog, therefore, is not to repeat what many have already said. My purpose is to determine what the research really says about vegan diets.

The Claim:

If you eat a whole-foods, plant-based vegan diet, you will not get heart disease, diabetes, or other symptoms of metabolic syndrome. If you already have these diseases, a vegan diet will cure them.

Results from initial search:

There are many reasons why people might choose a vegan diet. Some believe it’s healthier than eating meat while others are more concerned about the environment and animal welfare. It’s widely accepted a vegan diet can be a very healthy option as long as you are sure to get a variety of proteins from different grain and legume combinations, supplement with vitamin B12, and possibly add other supplements to get essential fatty acids.

Most experts also agree that farmed animals are causing plenty of environmental harm, not to mention harm caused to the animals themselves. These concerns are certainly valid. Some people argue that if you purchase animal products from local farmers markets, you can avoid supporting factory farming and have less impact on the environment. Others disagree, stating that all animals fear death and should not be slaughtered for food.

The environmental and animal welfare aspects of a vegan diet, while important, are not within the scope of this blog. I will say that personally, I believe it’s important to support local farms and farms that allow animals to live as naturally as possible. The “Certified Humane” stamp on some animal products is the best indicator of humane animal treatment that can be found at typical grocery stores. Other markers such as “pasture-raised” or “free range” are misleading and practically meaningless when issued by the USDA.

 When it comes to the health benefits of a vegan diet, there is quite a bit more controversy. Some pro-vegan arguments include:

  • Vegan diets help mitigate some of the world’s biggest health issues such as obesity, diabetes, heart disease and cancer because plants are high in fiber, vitamins, minerals, and antioxidants while being low in saturated fat.
  • Processed meat causes cancer.
  • Animal products contain saturated fat which caused heart disease.
  • You can get more than enough protein by eating and combining high protein grains and legumes.
  • Groups of people who live the longest usually eat vegetarian or vegan diets.
  • Vegan diets are better for you gut health.

Some pro-omnivore arguments include:

  • Iron, zinc, calcium, vitamin B12, DHA and EPA are lacking in vegan diets. Over time, these cause bone loss, heart disease, and other health problems.
  • People have been eating meat and animal products for thousands of years. Refined grains and sugar are really what’s causing increased rates of metabolic syndrome and cancer.
  • It can be difficult to get enough complete protein through plant sources alone.

Follow-up questions

  • If you supplement and make sure you’re eating foods high in protein, is it really that hard to get all your nutrition from a vegan diet?
  • It seems the jury is still out on saturated fat. Could it affect different people differently?
  • Have studies compared vegan diets to other whole food diets that include meat or just to the standard American diet?
  • If vegans really do have better metabolic profiles, how much better are they?
  • Many studies may claim to demonstrate health benefits of vegan diets. Are there other studies that claim equivalent or even better health benefits of other diets?

Reader comments and questions (send me some!)

Peer-reviewed research

Inclusion criteria: search terms “vegan diet” on PubMed. Published in last 10 years. Reviewed first 5 pages of results. Vegan diet compared to another diet considered to be healthy. Outcomes related to disease markers for diabetes and heart disease in humans. Italics are my interpretation.

1.Veganism Is a Viable Alternative to Conventional Diet Therapy for Improving Blood Lipids and Glycemic Control. (2015)

No access to full text. Conclusion suggests vegan diets are somewhat better than healthy omnivorous diets to help people with type 2 diabetes and/or high cholesterol. The authors seem to have reviewed several studies to come to this conclusion. We can’t tell how much better vegan diets are or whether or not the results were clinically significant.

2. Beyond meatless, the health effects of vegan diets: findings from the Adventist cohorts. (2014)

Full text available. This study compares large groups of vegan/vegetarian, and omnivorous Adventists from several different studies. Vegetarians had a 55% lower chance of developing hypertension and a 25-49% lower chance of developing type-2 diabetes than omnivores. Vegetarians had a 23% lower chance of developing GI cancers, a 50% lower chance of developing colon cancer, and a 35% lower chance of developing prostate cancer. When vegans and vegetarians were separated out, the vegans had even lower chances of developing these diseases. This study only reported relative percentages, not absolute percentages. This study makes a good argument that a vegetarian diet is at least slightly healthier than a diet that includes meat in terms of chronic disease.

3. Vegan diet and blood lipid profiles: a cross-sectional study of pre and postmenopausal women. (2014)

Full text available. This study measured different types of cholesterol in vegetarians, vegans, and omnivores. We now know that HDL cholesterol is good and LDL cholesterol is bad. Many doctors look at the ratio of LDL to HDL and consider it to be a much better measure of health than looking at total cholesterol or LDL or HDL alone. This study says that in premenopausal women, a vegan diet decreases HDL, but does not decrease LDL. The vegetarian diet decreases HDL, but decreases LDL even more. Therefore, the vegetarians would have a better ratio than the vegans. The omnivore ratio was comparable to the vegetarians. The findings only applied to the premenopausal group.

4. Effect of a 6-month vegan low-carbohydrate (‘Eco-Atkins’) diet on cardiovascular risk factors and body weight in hyperlipidaemic adults: a randomised controlled trial. (2014)

Full text available. 50 people were divided into 2 groups of 25 (one group ate a low carb vegan diet while the other group ate a high carb vegan diet). After 6 months, only 13 people were left in the high carb group and 10 in the low carb group. It seems that the main finding in this study is that the diets aren’t easy to stick to. In the end, most people in the low carb group had better cholesterol than those in the high carb group. However, people in both groups made significant progress in terms of weight loss and cholesterol.

5. Effect of a Brown Rice Based Vegan Diet and Conventional Diabetic Diet on Glycemic Control of Patients with Type 2 Diabetes: A 12-Week Randomized Clinical Trial. (2016)

Full text available. A strict vegan diet controls blood sugar better than a healthy omnivorous diet, but for most people, it’s very hard to stick to. The difference between how much each diet decreased blood sugar was relatively small. However, the sample size was small and compliance with the diets varied.

6. Comparison of a Restricted and Unrestricted Vegan Diet Plan with a Restricted Omnivorous Diet Plan on Health-Specific Measures. (2015)

Full text available. 12 people ate a plant based vegan diet with no refined grains, sugar, or sweeteners. 12 people ate a similar diet, but were allowed lean protein and skim milk. 11 people ate a vegan diet, but were allowed refined grains, sugar, and sweeteners. Participants ate these diets for 21 days. All 3 diets showed improvements in health. Cholesterol was improved in the vegan and non-vegan groups who avoided refined grains and sugar. Cholesterol did not improve in the vegan group that continued eating refined grains and sugar. Blood pressure was reduced in all groups, but most in the vegan group that avoided refined grains and sugar.

7. Effect of diet on type 2 diabetes mellitus: a review. (2014)

No access to full text. Vegan, vegetarian, low carb, and Mediterranean diets have all helped people with type 2 diabetes to control their blood sugar. Different people respond differently.

8. A low-fat vegan diet and a conventional diabetes diet in the treatment of type 2 diabetes: a randomized, controlled, 74-wk clinical trial. (2009)

Full text available. 49 people were assigned to the low-glycemic vegan group and 50 to the conventional healthy diet group. The study lasted 74 weeks. Both groups improved in terms of weight, blood sugar, and cholesterol. Blood sugar and cholesterol improved significantly more in the vegan group than the conventional group.

9. Vegetarian diets and incidence of diabetes in the Adventist Health Study-2. (2013)

More than 40,000 healthy people were studied. They were categorized as either: vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). The researchers wanted to see how many developed diabetes over the next 2 years. Diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. After other lifestyle factors were controlled for, vegan and vegetarian diets (but not ones including fish) still offered protection against diabetes. Black people were more likely to develop diabetes than white people, but all people benefited from a vegetarian diet.

10. A two-year randomized weight loss trial comparing a vegan diet to a more moderate low-fat diet. (2007)

This is a randomized trial which can provide more reliable evidence than retrospective or observational studies. The researchers compared a low fat mostly vegan diet to a more traditional low fat/low cholesterol diet. However, the vegan diet did allow for a very small amount of meat and dairy. They also studied whether group support meetings were helpful. All participants were postmenopausal women. After 2 years, the vegan group had kept off about 3 kilograms whereas the control group had kept off about 1. This study only measured weight loss, but we know that being overweight is strongly associated with metabolic syndrome.

11. Comparative effectiveness of plant-based diets for weight loss: a randomized controlled trial of five different diets.

Full text not available. This study assigned 63 overweight people to vegan, vegetarian, pesco-vegetarian, semi-vegetarian or omnivorous diets. The vegan group lost an average of 7.5% of their body weight after 6 months. The other groups lost about 3%. Calories were not purposefully restricted.

What we know and don’t know

Looking at these studies, we can see that a vegan diet may be a good idea for some people. But, as expected, the results were not as incredible as our favorite Netflix documentaries would suggest.

All of the research I found supports a vegan diet in people who are at risk for metabolic syndrome. However, the effects of the diet were modest and some studies show the diet can be hard to stick to. When people are allowed to eat freely without counting calories, they tend to lose only 5-10% of their body weight by switching to a vegan diet. This moderate amount of weight loss does seem to help reduce other markers of disease, so a vegan diet is likely to help people at risk. However, it is an overstatement to say that a vegan diet cures metabolic diseases.

The studies here did present a few flaws/risks that should be mentioned. First, vegan diets tend to lower good cholesterol (HDL) more than bad cholesterol (LDL) in some people. This may actually give some people a worse overall cholesterol profile. Additionally, most of these studies didn’t parse out different populations of people. For example, we know the diet can help middle aged people who are overweight, but is it also good for children, athletes, or expectant mothers? There are studies available to address these questions, but they were not reviewed here. It does seem that for the populations studied, it is reasonable to get all your nutrition from a vegan diet plus a vitamin B12 supplement.

Several of these studies found that reducing or eliminating refined grains and sugars had equal or even better results than avoiding animal products on health outcomes. Many did not allow the vegan group or the control group to eat refined carbohydrates because they purpose was to compare a vegan diet with another “healthy” diet. This suggests that a diet low in processed foods is healthier than a diet low in animal products, but, that a diet low in both categories of foods may be best.

In these studies, saturated fat was assumed to be “unhealthy” from the beginning. Therefore, it is difficult to determine what effects would be seen if saturated fat levels were increased. Other studies do address this question, but not within the context of a vegan diet.

It is important to remember that in all studies that are not double-blind, randomized, controlled, and include placebo, there is some room for bias. These studies generally found somewhat better health outcomes for vegans than for other groups. There are other studies that show better outcomes for other diets such as Mediterranean or paleo. These diets could each deserve their own blogs.

Conclusions and Applications

This research confirms one of my favorite quotes by author Michael Pollan.

Eat food, mostly plants, not too much.

Over and over we see that these are words of wisdom to live by if you want to be as healthy as possible. I might add slightly alter the quote to include the words “ethically sourced” if it were me.

Please share your comments and thoughts!


Does Sensory Integration Therapy Work?

Fidget toys are all the rage these days. You probably know someone who swears they help kids focus. You may even use them yourself. Fidget toys are just one of the many compensatory items that may be recommended for children with sensory processing disorder. If you’ve never heard of sensory processing disorder, here’s what you need to know. In the 1970s, Dr. A. Jean Ayres, occupational therapist, first described sensory processing difficulties. She explained that people make sense of the world through 7 senses: vision, hearing, taste, smell, touch, proprioception (sense of body awareness) and vestibular sense (sense of movement).  A person may be overly (hyper) or under (hypo) sensitive to one or more of the 7 senses.

The Claim:

Sensory integration therapy (SIT) teaches the brain to respond in a more organized (appropriate) way to sensations and movement.

Let’s dig in!

Results from initial search:

A sensory processing disorder (also called sensory integration disorder/dysfunction) diagnosis is usually made by an occupational therapist through a series of checklists by observing the child and interviewing the caregivers. The sensory problems generally affect the child’s ability to learn, interact with others, and participate in daily activities. Most children on the autism spectrum are reported to have sensory processing disorder as well as many children with ADHD and even some children with no other conditions. Here are some examples of what sensory processing disorder might look like:

Hypersensitivity to sound: extreme responses to or fear of common sounds like flushing toilets, coughing, or clanking silverware; inability to tune out background noises

Hypersensitivity to touch: Avoidance of touching or hugging people; refusal to wear many types of clothing or extreme discomfort when tags are not cut from clothing; fear of touching messy things like food, glue or play-doh

Hyposensitive vestibular sense and/or proprioceptive sense: desire to run and crash into furniture or other objects constantly; Constant need to jump or swing; no fear of getting hurt

Sensory processing disorder is not recognized as a mental disorder in the ICD-10 and many doctors do not believe it really exists as a disorder on its own. Most psychologists do recognize that children have sensory challenges, but see them as part of another developmental disorder or delay, such as autism.

Occupational therapists, as well as some other educators and professionals believe sensory processing disorder is at the root of many behavioral and learning challenges and that it can be treated, to some extent, with sensory integration therapy. Sensory integration therapy looks at how a child processes each type of sensory input and recommends things that can be done to help the child normalize the way he or she interprets the input.

They believe they are helping to literally reorganize the sensory system in the brain rather than simply provide coping mechanisms and compensatory strategies.

This is thought to be achieved through a prescribed “sensory diet” individualized for each child. When the sensory diet is followed, the child is expected to become more tolerant of sensory input and more calm, alert and focused. Different activities are assigned depending on whether the sense needs to be heightened or attenuated. Here is an example of a sensory diet:

To help calm and organize the proprioceptive and vestibular senses: rock on a chair or horse, climb stairs, push a grocery cart or something heavy, wear weighted vests or blankets

To help arouse hyposensitive proprioceptive and vestibular senses: use more erratic motion such as running, playing catch, and spinning around

To help organize touch, use textures and deep pressures such as: swaddles, bear hugs, joint compressions, finger paint, glitter glue, putty, rice bins

To organize the auditory sense, use: calming our arousing music, white noise, noise canceling head phones

To organize vision, use: sunglasses, lava lamps, mobiles, drawing, minimal patterns and clutter, non-fluorescent lighting

To organize smell and taste, use: essential oils, candles, warm and cold foods, blow bubbles, suck through straws

Follow-up questions:

    • How are brains of people with sensory problems different?
    • Does SIT really make changes to the brains of these people? Can we see the changes or measure them indirectly?
    • Even if the brain isn’t actually changing, can sensory diets help children learn, focus, and be more successful in relationships with others?

Reader comments

    • Most of my readers claim to either: work with or know people with sensory challenges, or have sensory challenges of their own. I would love to hear what’s worked for you! If you are an occupational therapist, your expertise is welcome!

Peer reviewed research:

  • Sensory integration therapies for children with developmental and behavioral disorders. (2012)
    • Summary of report: It is unclear whether children who present with sensory-based problems have an actual “disorder” of the sensory pathways of the brain or whether these deficits are characteristics associated with other developmental and behavioral disorders. Because there is no universally accepted framework for diagnosis, sensory processing disorder generally should not be diagnosed. Other developmental and behavioral disorders must always be considered, and a thorough evaluation should be completed. Difficulty tolerating or processing sensory information is a characteristic that may be seen in many developmental behavioral disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, developmental coordination disorders, and childhood anxiety disorders. Occupational therapy with the use of sensory-based therapies may be acceptable as one of the components of a comprehensive treatment plan.
  • Occupational therapy and sensory integration for children with autism: a feasibility, safety, acceptability and fidelity study. (2012)
    • Ten children diagnosed with autism spectrum disorder ages 4-8 years received intensive occupational therapy intervention using sensory integration principles following a manualized protocol. Measures of feasibility, acceptability and safety were collected from parents and interveners, and fidelity was measured using a valid and reliable fidelity instrument.
    • The intervention is safe and feasible to implement, acceptable to parents and therapist, and therapists were able to implement protocol with adequate fidelity.
    • This study did not measure whether the therapy actual worked as purported.
  • Pilot study: efficacy of sensory integration therapy for Japanese children with high-functioning autism spectrum disorder. (2014)
    • 20 children with high functioning autism (IQ of 70 or above) who had previously received therapy were studied. 8 children had received individualized sensory integration therapy and 12 children had received traditional group therapy.
    • The Miller Assessment for Preschoolers (Japanese version) was given to each child before and after 8-10 months of treatment. The results showed that Total score and all Index scores except for Verbal Index increased significantly in the SIT group, while only Total score increased in the GT group. Furthermore, the SIT group showed more improvement compared with the GT group in Total score and on Coordination, Non-verbal, and Complex Index scores.
    • The study had several limitations including testing group vs. individual therapy and being an analysis of previously collected data. Evidence for the efficacy of sensory integration therapy based on this study is present, but weak.
  • Parents’ explanatory models and hopes for outcomes of occupational therapy using a sensory integration approach. (2014)
    • Summary: 275 Parents hoped occupational therapy would help their children develop self-understanding and frustration tolerance to self-regulate their behavior in socially acceptable ways. They specifically wished for improvements in: self-regulation, interaction with peers, improvement in skilled motor activities, and self-confidence.
    • This study did not test whether sensory integration therapy worked; only what outcomes parents hoped for.
  • State of measurement in occupational therapy using sensory integration. (2014)
    • This article discussed how sensory integration therapy is being measured. The authors stated the need for additional measurement tools that take into account: descriptions of the child, how well the therapist or patient adhered to the treatment, dosage of treatment, outcome measurements with qualitative and quantitative data.
    • This article basically stated that sensory integration therapy needs to be measured more accurately.
  • An intervention for sensory difficulties in children with autism: a randomized trial. (2014)
    • 32 children ages 4-8 with autism and IQ greater than 65 were divided into treatment and control groups. The treatment group received sensory integration therapy and the control group did not. Some members of both groups received other types of therapy too, such as ABA.
    • The sensory integration group scored significantly better than the control group on several measures of the Goal Attainment Scale including self-care, social activities, and decreased caregiver assistance.
    • This study used more rigorous methods than most others, but still had flaws. The number of participants was small and all patients had a relatively high IQ.
  • A systematic review of sensory-based treatments for children with disabilities. (2015)
    • Thirty studies involving 856 participants met our inclusion criteria and were included in this review. Considerable heterogeneity was noted across studies in implementation, measurement, and study rigor. This means the studies were very different in quality and how the therapy was carried out.
    • The research on sensory-based treatments is limited due to insubstantial treatment outcomes, weak experimental designs, or high risk of bias.
    • The systematic review concluded that there is insufficient evidence to support the use of sensory integration therapy.
  • A systematic review of sensory processing interventions for children with autism spectrum disorders. (2015)
    • This systematic review examined the research evidence (2000-2012) of two forms of sensory interventions, sensory integration therapy and sensory-based intervention, for children with autism spectrum disorders and concurrent sensory processing problems.
    • “Sensory integration therapy” was defined as clinic-based interventions that use sensory-rich, child-directed activities to improve a child’s adaptive responses to sensory experiences. “Sensory-based interventions were characterized as classroom-based interventions that use single-sensory strategies, for example, weighted vests or therapy balls, to influence a child’s state of arousal.
    • 5 studies used sensory integration therapy and 14 studies used sensory-based intervention. Two randomized control trials using sensory integration therapy found positive effects using Goal Attainment Scaling (a popular and reliable way test to measure progress). The other 3 studies found positive effects for reducing behaviors linked to sensory problems. Few positive effects were found in sensory-based intervention studies.
    • This study also emphasized the need for more rigorous trials and better measurements.

What we know and don’t know:

  • These 8 articles were the only relevant studies I could find when searching PubMed. I would imagine there may be more research out there in journals specific to occupational therapy. I’m not sure why my search didn’t yield more results, especially since some of the studies I found were reviews of several others.
  • From what I found, it seems like the way SIT is implemented varies greatly and is hard to measure. Many measurements are subjective (looking at results such as whether the parents think the intervention is working). It may also be hard to tease out whether the SIT was what helped the child make progress or whether it might have been something else like behavior modification or maturity.
  • None of the research I found attempted to prove that children with sensory processing disorder had real neurological differences. They also did not attempt to show that after treatment, the children’s brains looked more like those of children without sensory processing disorder.
  • A few studies had promising results. Here’s what they had in common:
    • They measured pre and post treatment via the goal attainment scales which breaks down precisely how proficient a child is at a task/skill and how much help they need.
    • Therapy was provided to each child individually and not in a group setting.
    • Progress was reported in terms of the child getting better at functional skills, not having a more “normal” sensory processing system.

Conclusions and applications:

  • So, does sensory integration therapy change the brain? I wasn’t able to find any evidence that this is true. Does sensory integration therapy work? Maybe. From what I’ve learned, it seems that some children get better at things like self-care skills, social skills, and compliant behavior when they have SIT. My inclination is that the sensory diet can help get a child’s body and mind in a state more ready to learn. For example, some people are able to focus on school work better when Mozart is playing in the background while other people need complete silence. Many children are able to sit at their desks and focus much better after an hour of recess than without. I may be wrong, but right now, the theory that sensory integration therapy changes the sensory system neurologically is more of a hypothesis. There is not any evidence to support that notion.
  • Should occupational therapists continue using SIT? There definitely needs to be more high quality research in this area. For now, though, I think SIT should be used as a strategy or technique to help children improve other skills. This is the way I see SIT used most commonly today. Therapists often use sensory organizing strategies like brushing or weighted vests to help a child calm down and focus on a task. So, indirectly, it’s probably making a difference, at least for some kids. However, if the therapist, for example, said they were having a child swing in order to organize the child’s vestibular system, there may be a problem. There isn’t any evidence to support that swinging (or any other activity) can change the vestibular system.

That’s my 2 cents based on what I found in the research so far. I’m always open to learn more. What do my OT friends think about SIT and how it should be used?






Are Diet Sodas Really That Bad?

Today I’m reviewing one of the topics that interest me the most: Diet Coke. I’m one of the weirdos who actually likes the taste of Diet Coke better than regular Coke. I think it’s because Diet was usually what we had in my house growing up. And also because it doesn’t leave my teeth feeling all grimy like regular Coke. I gave up Diet Coke all together from about 2012-2015 after hearing about how terrible it was, even compared to sugary drinks. However, lately I’ve been skeptical of most health claims and decided it probably wasn’t a big deal. Out of my own curiosity and because of requests from other readers, today I’m giving artificial sweeteners the full review.

  1. The Claim

Regular soda is bad for you, but diet soda is even worse. It makes you gain even more weight and causes cancer. It’s a neurotoxin and is basically the same as drinking formaldehyde.

  1. Results from Initial Search

I trolled the internet for hours just to see what I would find. The internet was pretty split, just as it is for most controversial health claims. A few of the sites making diet drinks out to be the devil were:,, Dr. Axe,, and MD

These sites made claims that diet drinks trick your taste buds into craving sweeter foods and overcompensating for the calories not provided in the drink. Some state diet drinks trigger insulin and glucose intolerance leading to type 2 diabetes, weight gain, heart disease, and other symptoms of metabolic syndrome.

Other health problems they considered to be associated with diet drinks included: kidney damage, tooth erosion, compromised lungs, migraines, depression, anxiety, short term memory loss, multiple sclerosis, fibromyalgia, hearing loss, fatigue, brain tumors, epilepsy, chronic fatigue syndrome, birth defects, Alzheimer’s, ADHD, Parkinson’s, gut dysbiosis, DNA damage causing breast cancer, liver cancer, lymphoma, and leukemia, urinary and bladder cancer, depression, and lower bone density.

Some sites, such as WebMD,, and were more cautious with their claims. They generally agreed that drinking diet soda didn’t help people lose weight and that it only caused cancer when given to lab animals in amounts that greatly exceed the acceptable daily intake (ADI). However, they supported the notion that people probably give themselves permission to eat other unhealthy foods to compensate for the diet soda. They also agreed that diet soda increases a person’s risk for diabetes. These sites were careful to say that just because conditions like diabetes and weight gain were associated with drinking diet soda, diet soda was not necessarily the cause. Perhaps people who know they are at risk for metabolic syndrome choose to drink diet soda more often than the general population.

Finally, several sites claim diet soda probably doesn’t cause any health problems if limited to 1-2 cans per day, with the exception of tooth decay. However, tooth decay is caused by the acidity of the drink, not the artificial sweetener.  These sites include: Mayo Clinic,, and (American Cancer Society).  They say there is no evidence to suggest diet soda causes weight gain, spikes insulin levels, or inhibits fat loss. Evidence for overcompensation is mixed and metabolic syndrome associations are confounded by other dietary behaviors. The American Cancer Society fights the formaldehyde claim by explaining that the amounts are not harmful. Methanol from fruit juice breaks down into 10 times more formaldehyde than aspartame. They also state that the FDA sets a max daily safe amount of each artificial sweetener (acceptable daily intake) which is set to many times less than the smallest amount that could cause concerns in lab animals. An average size person would need to drink 19 cans of diet soda per day to reach levels that might be dangerous. The exception to this is people with Phenylketonuria (PKU). This is a rare genetic disorder where people can’t break down phenylalanine found in many foods. These people should avoid diet soda.

  1. Follow-Up Questions

Once again, I’ve found that I need to narrow my focus. How should I do this? I decided to focus on the middle group from the list above. This is the group that regards diet soda with caution. They don’t claim it causes every health problem known to man, but they are concerned that it may paradoxically contribute more to weight gain than weight loss. They also believe diet soda may contribute to metabolic syndrome, especially type 2 diabetes. This seems like the area with the most debate and valid health concerns.

There may be evidence to link artificial sweeteners to other health risks, but these will have to be explored more in depth at another time. My peer reviewed research below was narrowed to focus mainly on artificial sweeteners and weight gain/metabolic syndrome. You will notice that some of the experimental designs I reviewed looked at other health effects along with weight gain and metabolic syndrome markers.

  1. Reader Comments

None yet. Please leave me questions and/or articles you’ve found on topics you’d like me to explore!

  1. Primary Source Review

The first group of studies is in chronological order and generally concludes that artificial sweeteners are safe and may help with weight loss. The second group is also in chronological order and generally concludes that artificial sweeteners may be harmful and do not help with weight loss.

Group 1

  • Effect of drinking soda sweetened with aspartame or high-fructose corn syrup on food intake and body weight. (1990)
    • Healthy, normal-weight people were divided into groups that were given either aspartame sweetened soda or soda with high fructose corn syrup. They were allowed to eat their regular diets. A control group that was not given soda was also included.
    • Results: The group that got diet soda ate fewer calories than the control group during the 3-week study. The males that drank diet soda lost weight, but not the females. All members of the group that drank regular soda gained weight. Both the diet and regular soda groups ate less sugar in other forms than the control group without affecting intake of other nutrients. Researchers concluded that diet soda reduces sugar intake and may help control calorie intake and body weight.
  • Effects of consumption of caloric vs noncaloric sweet drinks on indices of hunger and food consumption in normal adults. (1991)
    • 20 healthy subjects consumed water, aspartame, saccharin or sucrose (sugar) sweetened drinks 3 hours after breakfast.  The subjects recorded how hungry they felt 15 and 45 minutes after their drink. Researchers also measured how much they ate at lunch.
    • Hunger reports were highest for the people who drank water and lowest for the people that drank sugar. There were no differences in how much people ate at lunch.
    • Results: artificial sweeteners do not increase hunger or food intake.
  • The effect of aspartame as part of a multidisciplinary weight-control program on short- and long-term control of body weight. (1997)
    • 163 obese women were divided into an aspartame group and a non-aspartame group during a 19 week weight loss program, a 1 year maintenance program, and a 2 year follow up period.
    • During the weight loss program, both groups lost about 10% of initial body weight.
    • After the 1 year maintenance, the aspartame group regained 2.6% of the weight and the non-aspartame group regained 5.4% of the weight.
    • After the 2 year follow up, the aspartame group regained 4.6% of the weight and the non-aspartame group regained 9.4% of the weight.
    • Researchers suggest including aspartame in a long term weight loss program may help with maintenance.
  • Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. (2009)
    • Literature review conclusions: People who consume artificial sweeteners generally do not compensate by eating more. The addition of artificial sugar poses no benefit for weight loss or reduced weight gain without purposeful calorie restriction. Consuming artificial sweeteners probably does not contribute to weight gain or obesity.
  • Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies. (2014)
    • 15 randomized control trials (RCT) and 9 prospective cohort studies (PCS) that looked at the relationship between low-calorie sweeteners and body weight were reviewed.
    • The randomized control trials associated low calorie sweeteners with reduced body weight, BMI, fat mass, and waist circumference.
    • The prospective cohort studies found that low calorie sweeteners were not associated with body weight or fat mass, but were associated with higher BMI.
    • RCTs provide more reliable evidence than PCSs. Therefore, researchers suggest substituting artificially sweetened beverages for regular calorie versions may result in moderate weight loss and be useful on a maintenance plan.
  • Substitution of sugar-sweetened beverages with other beverage alternatives: a review of long-term health outcomes. (2015)
    • 6 cohort studies and 4 RCTs with acceptable to high quality ratings through 2013 were analyzed.
    • All studies associated substituting sugar sweetened beverages with other types of beverages (did not specify) with lower weight gain.

Group 2

  • Effects of artificial sweeteners on body weight, food and drink intake. (2010)
    • Mice were divided into 2 groups: control and artificial sweetener. The mice who were fed artificial sweeteners were given the acceptable daily intake which can be compared to reasonable human consumption. All mice were allowed to eat as much regular chow as they wanted.
    • Results: consumption of artificial sweeteners resulted in significantly increased body weight even though food intake was the same for all groups.
  • Cytotoxic effect of aspartame (diet sweet) on the histological and genetic structures of female albino rats and their offspring. (2012)
    • Rats were divided into control groups and experimental groups. Experimental groups were fed the acceptable daily intake of aspartame.
    • Every 2 weeks, measurements were taken. Researchers found that the experimental groups had decreased body weight, high histological lesions, increases in chromosomal aberration and DNA fragmentation compared to controls.
  • Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake levels. (2013)
    • Rats were divided into 3 groups and fed either: yogurt with sucrose (sugar), yogurt with saccharin, or yogurt with aspartame. Amounts of sweetener were a reasonable amount that could compare to levels of human consumption. Physical activity was restrained
    • Conclusion: After 12 weeks, there was no difference in caloric intake among groups. The groups fed artificial sweeteners gained more weight than the group fed sugar. Researchers think this is due to either retention in fluid or decreased physical activity.
  • Effects of a nonnutritive sweetener on body adiposity and energy metabolism in mice with diet-induced obesity. (2014)
    • Obese mice were divided into 3 groups: sugar, artificial sweetener, and water. Amounts were consistent with what might be consumed by a human. After 4 weeks, measurements were taken.
    • Results: The mice that drank sugar had increased weight, body fat and hyperglycemia compared to the others. The group that drank artificial sugar had increased body fat, hyperinsulinemia, leptin levels and triglycerides compared to controls.
  • Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach. (2015)
    • Rats were divided into 5 groups: control, acceptable daily dose aspartame, acceptable daily dose saccharin, 4 times daily dose aspartame and 4 times daily dose saccharin
    • After 8 weeks, rats given artificial sweeteners had significantly reduced weight. However, they also had increased risk of liver cancer due to decreased suppression of a tumor gene, lower antioxidant levels, and “histological changes reflecting the hepatoxic effect of aspartame and saccharin”.
  • Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame. (2015)
    • I did not have access to the full article
    • Results: When female animals consume artificial sweetener during pregnancy, their offspring are more likely to have negative outcomes in adulthood including: higher consumption of sweet foods, increased blood glucose, LDL and triglycerides. The effects were more pronounced in males than females.
  • Artificial sweeteners are not the answer to childhood obesity (2015)
    • I did not have access to the full article
    • Artificial sweeteners are associated with increased risk of the same chronic diseases as sugar consumption. Researchers are not sure exactly why, but make several suggestions:
      • Diminished release of hormones involved in blood glucose regulation
      • Altered gut microbiota which also may impair glucose regulation
      • Exposure to hyper-sweet foods may increase preference for sweetness
  • Low-calorie sweetener use and energy balance: Results from experimental studies in animals, and large-scale prospective studies in humans. (2016)
    • This is a review of animal and human studies.
    • Researchers state that both animal and human studies find that low calorie sweeteners are associated with weight and fat gain, obesity, cardiometabolic risk, and even total mortality even when other lifestyle factors are controlled for.
  • Aspartame intake is associated with greater glucose intolerance in individuals with obesity. (2016)
    • Cross-sectional survey, nationally representative sample. 2856 adults tested. Results are based on what people in the study reported that they ate or drank within the last 24 hours.
    • Discussion: aspartame is associated with obesity-related deteriorations in glucose tolerance and fasting glucose. Consumption of aspartame may be associated with greater diabetes risk in people who are obese. Aspartame was related to impairments in glucose tolerance for overweight people, but not lean people. However, very few lean people reported consuming aspartame.
    • Conclusion: aspartame may be associated with greater glucose intolerance, particularly for those with obesity.
    • The authors don’t think people with diabetes purposefully chose diet sodas because they only included people who were not already diagnosed with diabetes.
  • Effects of long-term administration of aspartame on biochemical indices, lipid profile and redox status of cellular system of male rats. (2016)
    • Rats were divided into 4 groups and given either: water, 15 mg/kg aspartame, 35 mg/kg or 70 mg/kg daily for 9 weeks.
    • Results: the groups receiving 15, 35 and 70 mg/kg aspartame had “increased lipid peroxidation products in the kidney, liver and brain”. The 35 and 70 mg/kg groups had increased levels of total cholesterol, triglycerides, and LDL as well as other health problems.
  1. What We Know and Don’t Know

Looking at these studies, we can see a few trends. First of all, diet soda seems to be pretty bad for rodents. Not a single study using mice or rats found the artificial sweetener to be harmless. The studies I reviewed all gave the rodents small amounts of sweetener that could reasonably be consumed in an equivalent ratio by humans. So, if mice and rats have fat gain, higher LDL and triglycerides, glucose intolerance, liver cancer, and chromosomal problems at low levels of consumption, are humans at risk too? Maybe. All of these rodent studies have been done fairly recently (many published in 2015 and 2016) and have not been repeated on humans. I’d be willing to bet this is because humans are harder to control and have much longer life spans. 3 weeks in mouse time is probably something like 3 decades in human.

The studies involving humans were mostly done in the 90’s. They looked at large groups of people and collectively determined mild weight benefits for people drinking diet sodas compared to regular sodas. They didn’t usually measure the same other kinds of health outcomes as the rodent studies. We don’t really know how artificial sweeteners affect us at a metabolic level over long periods of time because there are so many confounding variables.  There is some consistency when it comes to people who are already overweight or diabetic. These people seem to experience more glucose intolerance related to artificial sweeteners than healthy people at lower body weights.

During my research I didn’t come across any overt conflicts of interest. However, some may exist on either side of the fence.

  1. Conclusions and Applications

I was actually quite surprised at the end of this one. I had initially thought the research would show artificial sweeteners to be harmless at reasonable doses. I figured the rodent studies would reflect very high levels of sweetener being force fed until poor health outcomes were reached. I was wrong about this. Mice and rats had some pretty alarming health outcomes at fairly low doses after just a few weeks. As the dose increased, health decreased. The human studies, even the RCTs, were broad and outdated. They relied on measurements such as BMI which have little to do with actual health. Their outcomes showed very modest weight reductions and didn’t delve deeply into other components of metabolic syndrome.

In my review, I mainly focused on weight, diabetes, and metabolic markers. I didn’t get into the other issues such as cancer and neurotoxicity. Admittedly, I think arguments claiming diet soda causes these problems are fairly weak, but I might be surprised to see what I find here as well.

My personal conclusion is that diet sodas are probably just as bad for a person’s health as regular sodas, possibly in different ways. However, neither diet nor regular soda is going to kill you if consumed occasionally. Both diet and regular soda can be treated like dessert. Eat sparingly. I’d rather have ice cream for dessert anyway. As for beverages, Topo Chico for the win!

I would love to hear some opinions on this!

Does Gluten Cause Leaky Gut?

When I asked people for topics they’d like me to research, gluten was by far the most popular. We’ve all heard so much about gluten lately! Many people assume it’s unhealthy, but have no idea what it is. Companies are labeling their water “gluten free”.  Let’s clear up the mess.


To simplify, gluten is a protein found in wheat, rye and barley. It helps these foods maintain their shape and makes them light, fluffy and elastic.

So, if gluten is just a fluffy delicious protein, why do so many people insist it will make you sick?

Well, because in some people, it can cause celiac disease or maybe even other autoimmune diseases. In celiac disease, an immune response is triggered when people eat gluten which causes damage to the lining of the small intestine, bloating, diarrhea, cramping, heartburn, skin rashes, and other health problems.

But wait a minute you say, I know people who insist gluten will make EVERYONE sick, not just people who have celiac disease.  I’ve heard gluten causes leaky gut and leaky gut can cause all kinds of problems from inflammation to cancer to autism. Let’s investigate.

  1. The Claim

A large percentage of the population (generally somewhere between 10 and 100%) should not eat gluten because it can cause inflammation, leaky gut, digestive problems, learning disabilities, autoimmune diseases, cancer, autism, or other health problems.

  1.  Results from Initial Search

Just like when I first started researching GMO’s, I found an overwhelming number of blogs and websites discussing the dangers of gluten. Most of what I found focused on celiac disease and “non-celiac gluten sensitivity” which was described as something that may or may not exist on popular sites such as WebMD. Some sites described FODMAPS (Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols.) which are present in many foods and can be difficult to digest. They suggested these could actually be what’s causing sensitivity rather than the gluten. Some naturopathic, functional medicine and holistic medicine practitioners linked gluten to SIBO (small intestine bacterial overgrowth), candida (yeast), fungal overgrowth, and parasitic infections, all via leaky gut.

Then, I arrived on something I had never heard of called: ZONULIN.  After digging in deeper, zonulin seemed to be the most promising explanation for the possibility of gluten sensitivity. Therefore, I narrowed my search to focus on how gluten triggers zonulin and zonulin triggers leaky gut. Keep in mind, other things besides gluten may cause leaky gut. Gluten may cause other problems besides leaky gut. AND other things besides gluten may trigger zonulin. But, to keep it manageable, I decided to focus only on how gluten triggers zonulin which then triggers leaky gut.

  1. Follow-Up Questions

What is zonulin? Zonulin is a protein that modulates the permeability of tight junctions between cells of the wall of the digestive tract. In other words, it is a protein that opens and closes spaces between cells in the gut lining to let nutrients out into the bloodstream while keeping toxins in the intestine. It was discovered in 2000 by Alessio Fasano, M.D. Dr. Fasano found that when people eat gluten, one of the gluten proteins (gliadin) triggers the body to release large amounts of zonulin. This was especially true for celiac patients. The zonulin then opens the spaces in the gut lining. Then, gluten and other molecules are released out into the bloodstream. In people with celiac disease, the body sees the gliadin as an intruder and responds by creating antibodies which attack the intestine. This “attack” does not occur in all people. These processes have been widely researched and accepted by the scientific and medical communities as they relate to celiac disease.  Research is being conducted to determine who might be susceptible to gluten-related diseases in addition to those with celiac. The research is now focusing on how/whether zonulin (and gluten) may be linked to other autoimmune conditions such as insulin dependent diabetes, multiple sclerosis, and rheumatoid arthritis.

  1. Reader Comments

I was provided with 2 peer-reviewed research articles describing how zonulin works by my CrossFit coach. These are discussed in the primary source review below.

  1. Primary Source Review

(Note that these studies are out of chronological order. I have them listed in the order that I reviewed them which is completely random. I tried to rearrange them into chronological order, but found I would need to re-write definitions and explain ideas that I had already explained elsewhere. So I left them out of order. Some parts of the review would make more sense if they were described in chronological order. This blog is definitely a learning process.)

  • Zonulin, regulation of tight junctions, and autoimmune disease (2102)
    • This article claims that the “upregulation” of zonulin in genetically susceptible people leads to a variety of autoimmune diseases. Zonulin upregulation is most commonly caused by ingesting gluten (gliadin) or by bacteria in the small intestine. When the opening of the gut lining is triggered by the bacteria, it is thought to be a defense mechanism to flush out unwanted microorganisms.
    • Celiac disease: This is fairly well understood. Gliadin triggers zonulin. Zonulin opens tight junctions between cells. Harmful proteins, bacteria, toxins, etc. escape. An immune response attacks both the escaped toxins AND the intestine. It is important to note that celiac patients have much higher zonulin levels than controls EVEN when on a gluten free diet.
    • Type 1 diabetes: I have to admit this portion was difficult to understand. The best way I can explain it is that the study found that increased intestinal permeability occurred 2-3 weeks before the onset of type 1 diabetes in mice. Similar findings occurred in studies with children. This suggests that the intestinal permeability is triggering islet autoimmunity (type 1 diabetes).
    • Treatment: Zonulin inhibitor AT 1001 is a drug that inhibits the release of zonulin. It has been shown to be very effective in human trials at preventing loss of tight junctions in the intestine. It prevented or lessened gastrointestinal symptoms of 2/3 of the participants. In rat studies, it prevented the “insult of pancreatic islets”, therefore preventing the onset of type 1 diabetes.
    • Conclusion of review:  Genetic predisposition, mis-communication between innate and adaptive immunity, exposure to environmental triggers, and loss of intestinal barrier function secondary to the activation of the zonulin pathway by food derived environmental triggers or changes in gut microbiota, all seem to be key ingredients involved in the pathogenesis of inflammation, autoimmunity, and cancer. In other words, you need certain genes, plus exposure to gluten, plus leaky gut in order to develop inflammation, autoimmunity and certain cancers.
    • Note: cancer, Crohn’s disease, schizophrenia, and chronic kidney disease were briefly discussed in association with the HP2 gene (described as alias zonulin) in this report. I was unable to interpret the content. If anyone wants to take a stab at it, feel free to help me understand.
  • Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms (2009)
    • This article is very similar to the one above.
    • It supports the hypothesis that a combination of genetic factors, environmental factors AND loss of intestinal barrier function are all necessary in order to develop an autoimmune condition, especially celiac disease and type 1 diabetes.
    • Conclusion of review: Loss of intestinal barrier function is needed in order to develop autoimmunity. Reestablishing the intestinal barrier function could then treat the autoimmunity.
  • Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines (2006)
    • Celiac and non-celiac ex vivo (outside of the body) human small intestines were exposed to gliadin. The intestines of celiac patients had sustained zonulin release whereas non-celiac intestines had a limited transient zonulin release.
    • The non-celiac intestines still experienced an increase in intestinal permeability, but it never reached the level of permeability of the celiac intestines.
    • Conclusion of study: gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules. This means that in test tubes, gluten caused some degree of “leaky gut” in all types of people. However, it was much more severe in celiac tissue.
  • Dietary intake of wheat and other cereal grains and their role in inflammation (2013)
    • Conclusions: The effects of gliadin on intestinal permeability and the immune system have been confirmed in humans. In celiac disease and gluten-sensitive individuals, adverse reactions are apparent. They recommend highly controlled clinical studies involving patients suffering from other “inflammation-related diseases” and healthy people.  They state that most studies we have are confounded by other variables in people’s diets.
  • Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. (2011)
    • This article goes into great detail about how zonulin works. It’s way over my head.
    • It describes how zonulin has been proven to be involved in the development of: celiac disease and type 1 diabetes.
    • The authors hypothesize about how zonulin is playing a role in: asthma, multiple sclerosis, glioma, and inflammatory bowel disease.
    • They described how zonulin is a biomarker in autoimmune diseases, diseases of the nervous system, and neoplastic conditions.
    • Conclusions: Exactly the same as the first two articles. Increased permeability occurs before disease. Therefore, disease might be prevented or treated by decreasing permeability.
  • Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. (2008)
    • Researchers studied ex-vivo small intestines from mice. They found that gliadin binds to CXCR3 (a receptor protein) and leads to MyD88-dependent zonulin release and increased intestinal permeability.
    • This means, they figured out a little more about how zonulin causes the spaces between cells in the gut lining to open. Keep in mind, they used mouse intestines in test tubes.
  • Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. (2015)
    • 23 patients total were studied. They were split into 4 groups: celiac patients with active disease, celiac patients in remission, non-celiac patients with gluten sensitivity, and non-celiac controls.
    • Ex-vivo human duodenal biopsies were incubated with either gliadin or media alone (control)
    • Conclusion: All groups showed a greater increase in permeability when incubated with gliadin vs. media alone. The highest rates of increased permeability were in the patients with active celiac disease and the patients who reported to be gluten sensitive.
  • A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. (2013)
    • A 4 week randomized control trial involving people with diarrhea-predominant irritable bowel syndrome (IBS-D) found that gluten alters bowel barrier functions, especially in genetically susceptible patients.
  • (2011)Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.
    • 34 patients with IBS, but not celiac disease, participated in a trial. They found that the group that received gluten rather than the placebo did experience more severe gastrointestinal symptoms.
    • However, they could not determine why. The groups showed no difference in intestinal permeability or other celiac markers.
  • (2011) Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity
    • This study had 3 groups: celiac disease, gluten sensitive, and gluten tolerant controls. They evaluated intestinal permeability using a “lactulose and mannitol probe”. This is a test to determine whether someone has increased intestinal permeability and is reported to have high sensitivity and specificity (it is good at identifying the people with leaky gut and the people without leaky gut).
    • They found that gluten sensitivity was not associated with increased intestinal permeability. In fact, the people with gluten sensitivity had LESS intestinal permeability than the CONTROL group.
  • (2016) Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases.
    • I did not have access to this article, but the abstract states, “This review focuses on the recent research implicating zonulin as a master regulator of intestinal permeability linked to the development of several chronic inflammatory disorders”.
  1. What we know and don’t know
  • We know…
    • Based on the research, I can say with certainty that intestinal permeability or “leaky gut” is a REAL thing. It’s not made up. Not pseudoscience. Many well-respected researchers have published studies proving that the spaces between the cells in the gut can be opened.
    • Zonulin is the only protein we know of right now that can cause the spaces to open.
    • People with celiac disease have higher levels of zonulin in their blood than other people, even when they have been on a gluten-free diet for years.
    • Gliadin (from gluten) causes increased production of zonulin in ALL people, but it causes a much greater increase in people with celiac disease.
  • We don’t really know…
    • If gliadin causes an increase in zonulin production in all people, and zonulin binds to receptors in the gut lining in all people to open the spaces, why doesn’t everyone test positive for leaky gut after eating gluten? According to test-tube studies, it seems like all people should be experiencing leaky gut in response to gluten. However, only people with celiac disease test positive for leaky gut given the lactulose-mannitol probe. Is there a problem with the test? Is something in the living body somehow preventing or quickly “cleaning up” the damage in healthy people? Were the test tube studies flawed?
    • If only people with celiac disease test positive for leaky gut after eating gluten, why does a gluten-free diet seem to help many people with IBS-D or self-reported gluten sensitivity?
    • If people with celiac disease continue to have much higher serum zonulin than controls years after starting a gluten-free diet, why don’t they continue to have symptoms?
    • Are there more independent studies to prove that a leaky gut is one of the key components in type 1 diabetes and other autoimmune disorders? Dr. Alessio Fasano is the lead author in the majority of these studies and reviews. Every study I’ve found related to leaky gut or intestinal permeability over the past 20 years references his work. He has created a medication to help prevent leaky gut. Is there a conflict of interest? Could he be exaggerating his claims?
      • Note: Dr. Fasano DOES NOT recommend a gluten free diet for everyone. He states that about 1 in 100 people has celiac disease, many more have an autoimmune disorder or gluten sensitivity, and these numbers are rising. He suggests a gluten free diet is only necessary for these populations. He also wants his treatment to be approved only as a backup for when these people may unknowingly encounter gluten (like when they eat at a restaurant). He also feels that gluten has been “sensationalized” as causing a number of unrelated conditions. As far as I can tell, he is widely respected among both the scientific/medical and naturopathic/functional medicine communities. Please let me know if you have any more information on how he’s received in the medical community.
    • We know that gut bacteria play a role in zonulin upregulation. Are there any other conditions or factors that may cause zonulin upregulation or leaky gut in some other way? Lifestyle factors have been proposed such as diets high in sugar and alcohol or obesity.
    • What is the current research on how zonulin or leaky gut might be associated with other conditions?
  1. Conclusions and applications
    • Wow, what do we do with all this knowledge and all this uncertainty? Here’s what I think. There is a LOT of well-respected, published research to show that gluten may be linked to autoimmune diseases for genetically susceptible people. There is also a lot of published research that shows that a gluten free diet can help people with IBS-D. And obviously, if you have celiac disease, you should not eat gluten.
    • I’d say it’s a good idea for people with a family history of celiac, IBS-D, type 1 diabetes, or even other autoimmune diseases to give the gluten-free thing a shot, if they think it might help. I would even say that ANYONE who wanted to give it a shot should go ahead and do so. There’s really no harm in replacing gluten containing foods with rice, oats, potatoes, or gluten free alternatives. See how you feel. If you like it, great. If it makes no difference to you, great. If it keeps you from eating junk food, great. Go FOR IT!
    • If you feel fine when you eat gluten (or drink beer), you’re probably really fine. Keep consuming gluten without guilt or worry. The evidence that gluten causes leaky gut in all people is limited to test tube studies only. In living healthy people, the testing shows gluten does not cause leaky gut, even in people who claim to feel much better when they don’t eat gluten. The lactulose/mannitol test is reported to have high sensitivity and specificity. This means it is good at telling who has a leaky gut and who doesn’t have a leaky gut. Researchers don’t have any clue why some people feel better when they go gluten free, but they acknowledge that these people aren’t making it up. It’s not in their heads.
    • There’s one guy, Dr. Alessio Fasano, who is really a leader in all this research. Some of his peers disagree with him and think he’s gone a bit too far in suggesting there could be links between gluten and say, cancer or asthma. Even he says he would not recommend a gluten-free diet to the majority of the population. THIS GUY EATS BURGERS…with the bun. And he thinks most people can do so with no problem.
    • Don’t waste your money. If you’re spending extra money to buy gluten-free alternatives and you can’t really tell a difference in the way you feel, you’re not doing yourself any favors.
    • So, what will I do with this information? I have chronic digestive problems, but I’ve already gone long periods of time without eating gluten (like 3 months at a time). I never noticed an improvement in my digestion. In fact, it got worse. I might try it again at some point if more convincing research comes out pertaining to my specific symptoms. Otherwise, I’ll rest assured that the alcohol in my beer and the sugar in my cupcake are definitely doing more harm than the gluten. That’s probably the simple truth for most of us. At the same time, your friend that swears she doesn’t feel good when she eats gluten probably isn’t a nut case. Respect that science doesn’t have all the answers to why gluten makes some people feel some kinda way.