Examine.com Blog - Interesting Revelations on Supplements

Posted by KamalPatel on Aug 25, 2015

We’ve just updated our page on Biotin, an essential vitamin, also known as vitamin B7. It was discovered in a yeast culture at the same time as several other B-vitamins.

Biotin was initially researched in the context of skin and hair health, and today it is almost exclusively sold as a dietary supplement marketed to improve skin, nail, and hair quality. However, biotin is plentiful in food and rarely needs to be supplemented.

Apart from removing all food containing biotin from your diet (which makes it nigh impossible to maintain a healthy diet) the only way to cause a biotin deficiency is by eating excessive raw egg whites. Egg whites contain a protein called avidin, which is destroyed when the egg is cooked. Avidin binds to biotin and eliminates it from the intestines before it is absorbed.

At the moment, biotin does not have much evidence to support its use as an aesthetics supplement. Though it is biologically possible that increasing biotin intake or normalizing a deficiency could improve nail, hair, and skin quality, there is only one study to date to support this claim. This study found that women supplementing 2.5 mg of biotin over six months experienced improved nail health, as they were suffering from brittle and splitting nails. There are no strong studies to suggest healthy people supplementing biotin would experience any benefits.

There is preliminary evidence to suggest biotin could have a mild anti-diabetic effect. Much more research is needed to confirm this hypothesis.

Biotin is an essential vitamin, but it’s an underwhelming dietary supplement. There is very little evidence to support its use as a health and beauty supplement.

Posted by KamalPatel on Aug 17, 2015


With so many low-carb trial results rolling in each year, you might think that it’s case closed: everything there is to know is known. But there are still a few key pieces missing, and one of those pieces has just been released in the form of a six-day feeding study. Why only six days? That can’t tell us anything, right? Read on to see how revealing this study actually was, as well as what it can’t show (and likely wasn’t designed to show).

Low-carbohydrate diets have become even more popular in the past few years, bolstered by the so-called “carbohydrate-insulin hypothesis of obesity”. This hypothesis suggests that carbohydrates are the main culprit of weight gain. Things get complicated here, because there are both practical factors (e.g. going low-carb means limiting your food options, which typically makes snacking on junk food more difficult) and physiological factors at play. For the latter category, advocates claim that you can harness the power of decreased insulin levels (from carb restriction) and lose more fat due to factors such as elevated free fatty acid release from fat cells and increased fat oxidation.

Some low-carb advocates believe that carbohydrates are uniquely fattening, due to the effects of insulin. Despite a plethora of studies on low carb effects, there are still important areas left to research.

Lo and behold, both meta-analyses and long-term trials often show low carb diets to be as good or better than other diets for weight loss. However, participants usually self-report their food intake, and the longer the trial, the more likely life will get in the way. It’s a catch-22 of sorts: you want long trials to make sure the diet is sustainable, but the longer the trial the more likely there will be unwanted variations in diet.

Despite all the low-carb trials of recent years, there was still a lack of highly-controlled studies that solely altered carbs and fat in participants living in (aka stuck in) a metabolic ward. To address this issue, Kevin Hall’s team at the National Institutes of Health designed a short-term study to isolate the different effects of a restricted-fat diet versus restricted-carb diet on body weight, energy expenditure, and fat balance.

Low-carb performs fairly well for weight loss in trials over the course of months. A recent short-term study controlled several extra variables to isolate the effects of carb reduction on fat loss.

The Study


The participants were 19 obese volunteers (ten males and nine females) with no apparent disease.

All participants were required to reside within a metabolic unit, where they …

  • First received a baseline weight maintenance diet for five days before being randomized to either ….
  • The Restricted Fat group or Restricted Carbohydrate group, where caloric intake was reduced by 30% from baseline for six days, by either fat or carb reduction.

The carb levels ended up being 352 grams for Restricted Fat versus 140 for Restricted Carb, and the fat levels 17 versus 108. In other words, (moderately lower carb than typical diets) versus (oh my goodness I can count my fat gram intake on my fingers and toes!).

This trial wasn’t designed to explore a real-life 100-gram-and-under low carb diet and especially not a ketogenic diet. Rather, it was a mechanistic study designed so that they could reduce energy substantially and equally from fat or carbs, but without changing more than one macronutrient. If they lowered carbs much more in the Restricted Carb group (like under 100 grams), they’d then have to go into negative fat intake for the Restricted Fat group. And negative fat intake is impossible (*except for in quantum parallel universes). One more note: all participants kept dietary protein constant and exercised on a treadmill for an hour a day.

19 study participants spent six days in a metabolic unit, eating either a moderately low-carb diet (140 grams) or a really darn low-fat diet (17 grams). The trial used these specific levels in order to achieve isocaloric diets with large carb/fat reductions, without having to alter more than one macronutrient.

After the completion of this first phase, subjects went home for a two to four week washout period where they resumed their normal eating habits. Participants then returned to the study center to undertake the same protocol except with switched intervention groups. So those formerly in the restricted carbohydrate group would now be in the restricted fat group, and vice-versa.

This crossover design was one of the many ways in which this trial was more stringent than most previous studies (other reasons are shown in the above graphic), since crossing over eliminates much of the variability that normal randomized trials have. Randomized trials may be considered the gold standard, but this trial was a mix between gold, platinum, and titanium. Very strong, very valuable. They even had participants wear accelerometers on their hips to measure physical activity.

The crossover design was one of many rigorous aspects of the study, along with a relatively large sample size for a metabolic ward study, highly controlled variables, and multiple accurate measurement techniques.

Why not use just DXA for measuring body composition?

The primary method used to measure body composition was to calculate the difference between dietary fat intake and fat oxidation, as measured in a metabolic chamber by indirect calorimetry, which estimates the heat released by a person based on the amount of O2 they consumed and CO2 they produced over a specific period of time. While indirect calorimetry isn’t perfect, it’s accurate and reliable enough to be the standard method used to measure energy expenditure in these types of studies.

Body weight and a dual-energy X-ray absorptiometry (DXA) scanner were also used, but the former can’t calculate body fat, and the latter isn’t sensitive enough to detect the minute difference in body fat loss that usually occurs between eucaloric diet interventions of different macronutrients.

DXA is quite accurate for changes over the long term, but indirect calorimetry is needed for a study of this nature.

Results, limitations, and other considerations

As expected, the researchers found that the Restricted Carb diet resulted in a decrease in daily insulin secretion (by 22%) and a sustained increase in fat oxidation, whereas the Restricted Fat diet resulted in no significant change of either. Despite this, by the end of the six-day period, the Restricted Fat diet resulted in greater fat loss than did the Restricted Carb group (463g vs. 245g).

The Restricted Carb dieters also had lower energy expenditure, to the tune of 98 fewer kcal/d compared to only 50 fewer in the Restricted Fat group. This isn’t enough calories to account for the difference in fat loss though. So why exactly did the Restricted Fat group lose that much more fat than the Restricted Carb group? The paper doesn’t get into this much, but gives some hints:

"Model simulations suggest that the differences in fat loss were due to transient differences in carbohydrate balance along with persistent differences in energy and fat balance. The model also implicated small persistent changes in protein balance resulting from the fact that dietary carbohydrates preserve nitrogen balance to a greater degree than fat”

… so their mathematical model points to a few possible minor factors, including a possible small benefit from dietary carbs benefiting protein balance. The use of this complex model to extend the results out further is interesting, as it partly compensates for having a six-day-only study (which is normal in the world of metabolic ward studies), but on the other hand the model isn’t something that is easily understandable by people other than the study authors. Maybe it’s really accurate, maybe it’s not.

“Very low carbohydrate diets were predicted to result in fat losses comparable to low fat diets. Indeed, the model simulations suggest that isocaloric reduced-energy diets over a wide range of carbohydrate and fat content would lead to only small differences in body fat and energy expenditure over extended durations.”

… ah, so if the researchers were able to reduce carbs to a much lower level (which they couldn’t, due to the study design factors described earlier), the diets would have actually led to similar weight loss. That makes those “New Study Shows Low-Carb Failure!” headlines sound a bit silly. If you take a really-darn-low-fat diet like the Restricted Fat diet, and compare it to a very-low-carb diet, you’re comparing two extreme diets and are more likely to get some metabolic advantage. Our bodies are typically accustomed to a somewhat balanced mix of fuel, and extreme macronutrient diets can probably game the system a bit for a modicum of extra fat loss.

More importantly, the authors put the results really important context: the differences in body fat loss between a wide range of different carb intakes are predicted to be very small (although the Restricted Fat diet was predicted to sustain its slight advantage over the course of months). This study wasn’t meant to demonstrate that low(ish) carbs are bad or low-fat is good, it was simply testing the hypothesis that carb reduction provides some secret sauce for fat loss in highly controlled conditions.

Surprisingly, the paper doesn’t mention the term “glycogen” even once. The study participants did an hour of incline treadmill a day, and since they had an average BMI around 36, that could mean a decent amount of glycogen burn with prolonged activity at a high body weight. So if liver and muscle glycogen happened to be relatively more depleted in the Restricted Carb group (since they replenished glycogen less by fewer dietary carbs), that might mean less fat loss in the short run, which may not apply as much to the long run when glycogen is in a steady-state.

Although the Restricted Fat group lost a bit more fat, fat loss over time was predicted to be similar over a range of carb intakes based on a mathematical model of metabolism. The main application of the study may be that despite a reduction in insulin, there was no extra fat loss advantage for the Restricted Fat diet … which more so argues against the “Carbohydrate-Insulin Theory of Obesity” rather than denying the efficacy of low-carb diets.

As always, there are a few more limitations to consider.

Due to the sample population chosen, the results of this study only apply to obese adults who are otherwise healthy. Further limiting the generalizability of the results, the tightly controlled study design does not accurately represent the free-living world, as most of us do not have strict external controls on our food choices.

And to repeat a very important point: this study was not meant to inform long-run dietary choices. In the long-run, the choice between restricting fat or restricting carbs to achieve a caloric deficit may come down to one thing: diet adherence.

While preference for certain foods may dictate which diet is easier to adhere to, this isn’t always the case. For instance, it seems that insulin-resistant individuals have an easier time adhering to a low-carbohydrate diet. Nowadays, new dieters often pair low-carb with higher protein, the latter of which can boost weight loss. And since there are plenty of high-sugar but low-fat junk foods (see Mike and Ike, et al.) but not so many high-fat but low-carb junk foods, low carb intakes can sometimes mean an easier time staying away from junk food when compared to low fat diets.

What about the six day trial duration? Does that mean the results are less valid? Well, it depends on the question you want answered. There aren’t any six-month-long metabolic chamber studies because they would both be ludicrously expensive and turn into studies of hospital patients rather than free-living people. So the researchers chose to shed light onto this question:

“Could the metabolic and endocrine adaptations to carbohydrate restriction result in augmented body fat loss compared to an equal calorie reduction of dietary fat?”

Quite clearly, the answer was no in this study. Many in the low-carb blogosphere have argued that six days was too short for fat-adaptation. Maybe, but the paper also said:

“Net fat oxidation increased substantially during the RC (restricted carbohydrate) diet and reached a plateau after several days, whereas the RF (restricted fat) diet appeared to have little effect.”

So restricting fat didn’t change metabolism much, while restricting carbs increased fat oxidation at first but not after a few days. It’s possible that other physiological mechanisms (e.g. mitochondria-related factors) may take longer to adapt (especially in very low carb / keto diets), but this wasn’t a study of keto diets, it was a study testing whether carb restriction leads to extra fat loss compared with fat restriction.

And while not without their limitations, free-living studies have generally shown that the low-carb groups tend to lose a bit more fat mass by the six-month mark (even when controlling for energy intake), but weight loss at the end of the trial tends to be similar. A big part of that is likely the increased protein that is typically coupled with lower carb. Those are things that media reports won’t mention when covering the current study -- context matters, and the totality of research suggests that media harping on each low-carb trial in isolation is dumb.


As usual, don’t bother with media headlines -- this study is NOT a blow to low-carb dieting, which can be quite effective due to factors such as typically higher protein and more limited junk food options. Rather, this study shows that a low-carb diet isn’t necessary for fat loss and that lowering carbs and insulin doesn’t provide a magical metabolic advantage.

It bears repeating: if you even try to apply this study to the real world of dieting choices, you will be frowned upon strongly. Even the lead author writes:

"Translation of our results to real-world weight-loss diets for treatment of obesity is limited since the experimental design and model simulations relied on strict control of food intake, which is unrealistic in free-living individuals."

This study was strictly meant to fill in a gap in the knowledge base of diet physiology. Got it?

If you need a broad and simple takeaway from this study, here is one: weight loss does not rely on certain carb levels or manipulation of insulin, it relies on eating less. Don’t be scared that eating carbs will cause insulin to trap fat inside your fat cells.

Posted by KamalPatel on Aug 6, 2015

Our tenth issue of the Examine.com Research Digest is out and this month our sneak peek is dedicated to one of your favorite sources of dairy-- cheese.

Although both cheese and meat are lumped into the “watch out!” category in heart-health recommendations, dairy products often show neutral or positive associations with cardiovascular health. In this month's sneak peek, we look at how cheese-rich diets fare in randomized trials when compared to other diets.

Serious about nutrition? Subscribe now for the latest in nutrition research.

Posted by KamalPatel on Jul 30, 2015

Today’s competitive society is full of stressed people. Extreme and debilitating distress, along with the fear of being judged and criticized by other people can cause panic and social anxiety, characterized by intense sweating, shaking, muscular tension, confusion, and an elevated heart rate. Social anxiety can make social situations very difficult, and if it occurs often, it can severely interfere with day-to-day activities, to the point where socially anxious people will avoid social interactions all together.

Social anxiety is also known as social phobia, as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). With up to 10.7% of people experiencing this condition at some point in their life, it is the third most common lifetime anxiety and mood disorder in the United States.

Social anxiety, a debilitating disorder that makes social situations extremely distressful and difficult to navigate, is the third most common lifetime anxiety and mood disorder in the United States.

Some research suggests that phobias are, at least in part, hereditary. In fact, a recent twin-study found that the sibling more likely to develop social phobia was the one that inherited genes predisposing them to neuroticism, a personality trait characterized by the tendency to respond poorly to stressors, often leading to the experience of negative emotions, such as anger, envy, nervousness, guilt, anxiety, and depression.

Treating social anxiety

Fortunately, there are a variety of potential treatments for this disorder. Traditionally, cognitive behavioral therapy and selective serotonin reuptake inhibitors (SSRIs) are used. Recently, probiotics (defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit to the host”) have shown promise as a supplement to the traditional treatments for social anxiety. Even though the research is still in its infancy, the fact that probiotics have excellent safety profiles and traditional treatments often only provide partial symptom relief makes them enticing treatment targets.

Research suggests that social anxiety may have a hereditary component. A couple common treatments exist, but they only provide a partial relief of symptoms. Fortunately, probiotics have shown some very early promise as a potential safe supplement to traditional treatments.

A recent study has been touted in the media as providing evidence for the anti-anxiety efficacy of consuming fermented foods that are likely to contain active probiotic cultures. Tantalizing headlines included “Sauerkraut Could Be The Secret To Curing Social Anxiety”. However, there were several limitations, warranting a much deeper look than most media outlets took. Let’s see what this study can really tell us, if anything.

The study

Researchers provided surveys to 710 university students to determine their level of social anxiety, neuroticism, and agoraphobia. The survey also asked how often the students exercised, and how often they ate fermented food. As hypothesized, students that ate more fermented foods tended to experience less social anxiety. Moreover, they found that, as seen in the figure below, social anxiety and neuroticism were positively correlated, and the more neurotic a person was the greater that chance that high fermented food intake might help reduce levels of predicted social anxiety.

However, before jumping to conclusions, there are a few extremely important limitations to consider. This was a cross-sectional study, which only shows correlation, not direct causality. The authors cannot be sure if it was the high fermented food intake that led to low levels of social anxiety or if low levels of social anxiety led to increased consumption of fermented food. It is also possible that an unknown variable caused both the increased consumption of fermented foods and the decreased social anxiety.

It’s also possible that some property of the foods other than their probiotic content affected social anxiety. Furthermore, the nature of a survey or questionnaire is subject to self-report bias. The authors can’t be sure if the participants were being truthful or could even remember exactly what they ate or how much they exercised over the past thirty days. And since the sample was made up of college students, the findings may not be applicable to the general population. Finally, and most importantly, lower levels of predicted social anxiety were also observed in participants that ate more fruit and vegetables, as well as those who exercised frequently. It’s not possible to determine whether exercise or fruit and vegetable consumption are confounding variables or not. This is especially important in light of a recent randomized control trial that found a reduction in symptoms of social anxiety following two months of aerobic exercise.

Based on survey data from 710 university students, a recent study found that consumption of fermented food likely to contain active probiotic cultures was inversely associated with predicted levels of social anxiety. However, due to many limitations and confounding variables, further research is needed before any assertions can be made.

That being said, this study is consistent with other clinical trials that have also demonstrated anxiolytic effects of pre and probiotics in humans. Unfortunately, the exact biological mechanism behind this is still unclear. However, according to preclinical animal trials, there is mounting evidence that certain gut microbiota can have anxiolytic effects through gut-brain pathways, possibly via the vagus nerve. Supporting these findings, the ability of the gut and brain to bidirectionally communicate through neural, endocrine, and immune pathways, also known as the gut-brain axis, has long been recognized, and recent research has made it increasingly clear that interactions with intestinal microbiota are an important part of this communication.

Furthermore, a couple more specific potential mechanisms for how the probiotics confer their anxiolytic effects have been proposed. For instance, given that research has found a positive association between gut inflammation and anxiety-like behaviors, some have hypothesized that probiotics could potentially colonize the gut, displacing species that are harmful to health, and, in turn, may reduce gut inflammation and the associated anxiety-like behaviors. Others have proposed the involvement of the serotonergic system in the neurobiology of anxiety, especially since research surfaced suggesting that certain intestinal microbiota can increase levels of tryptophan in the blood, and therefore potentially facilitate the turnover of serotonin in the brain.

Overall, research on probiotics and anxiety is still in its early stages. According to the authors, this is the first study to provide some extremely limited observational evidence for the efficacy of probiotic supplementation to fight, specifically, social anxiety, and thus, they did not mean to infer causality. Regardless, due to several limitations imposed by the study design, and the huge number of possible confounding variables, this study should solely serve as preliminary evidence, especially considering how strong of a confounding variable exercise is, as several papers have demonstrated its anxiolytic effects. However, if further well-conducted RCTs can suggest a causal role, independent of exercise and other possible confounding variables, probiotics or fermented foods consumption could potentially serve as great low-risk supplement to traditional treatment for social anxiety.

While the study results seem to support probiotic supplementation to help treat social anxiety, they can easily be misinterpreted in the midst of several limitations and confounding variables. The only thing we can state for certain is that further well-conducted RCTs are necessary before we make any conclusions about probiotics and their possible, low-risk health benefits.

Mood involves much more than social anxiety and probiotics-- check out our Stack Guide for mood and depression to learn more.

Posted by KamalPatel on Jul 16, 2015

On June 16, 2015, the United States Food and Drug Administration (FDA) announced their decision to eliminate trans fat from food in the United States by 2018, with a gradual phase-out period beginning immediately.

Take THAT, trans fat advocates! Hold on ... are there any trans fat advocates? While some dislike government regulation of foods and nutrients, there isn’t much debate about trans fat health effects anymore.

This brings up a question … if we all know that trans fat is bad, why is it still a public and personal health issue? Well, it is true that trans fat consumption has dipped considerably, with blood levels dropping by 58% in the 2000s. But incremental consumption of industrially produced trans fat is incrementally harmful, and the National Academy of Science has concluded that there is no safe trans fat dose.

So out of all the nutrient and nutrient-like substances out there, trans fat hold the dubious distinction of being one of the only categorically harmful ones. And you might not always know that you’re consuming trans fat, since some soybean and canola oils can have hidden trans fat inside.

Trans fat is an unsaturated fatty acid and a byproduct of partially hydrogenated oils (PHOs.) It is found in many processed food products, including margarine, coffee creamer, fast food, frozen pizza, snack foods and other baked goods. Trans fat is also found in some peanut butter. It is frequently used by the food industry because it improves flavor stability and shelf life of food. Since trans fat has a different melting point depending on how processed it is, it’s also a very flexible ingredient. But aside from these benefits, it seems that the primary reason trans-fat was added into the food system was the demonization of saturated fat by the USDA in the 1950s. By the 1980s, activist organizations were denouncing food manufacturers for using ‘unhealthy’ saturated fats in their foods, and endorsing trans fat as a ‘healthier’ alternative. Considering the benefits to shelf life, flavor stability, and flexibility, manufacturers gladly made the change.

Some types of trans fat are naturally produced by ruminant animals. This group of animals includes cattle, sheep, goats, buffalo, deer, and other animals with four stomach compartments. The first, and largest, part of the stomach, called the rumen, is where trans fat is produced. Humans can create trans fat through a commercial process called hydrogenation, in which hydrogen gas is boiled through oil (usually vegetable oil) to allow the oil to saturate, which determines its thickness.

Medical professionals consider trans fat to be one of the most unhealthy compounds found in today’s food. Trans fat consumption is associated with increased low-density lipoprotein cholesterol (LDL-C and inflammation), and decreased high-density lipoprotein cholesterol (HDL-C). These health risks can speed up the development of atherosclerosis (clogging and hardening arteries) and increase the risk of diabetes, coronary heart disease, and cardiac-related sudden death. However, a recent systematic review strongly suggests that these negative health effects are primarily attributed to the consumption of industrially-produced trans fatty acids (IP-TFA), but not ruminant-derived trans fatty acids (R-TFA). In fact, most animal models have demonstrated that IP-TFA and R-TFA have different effects on CVD risk factors. For instance, a rat study showed that supplementation with an R-TFA called Vaccenic acid had either a neutral or beneficial effect on CVD risk markers such as total cholesterol, LDL-C, and fasting and postprandial triglycerides.

Trans fat can be made commercially, or naturally by certain animals. It is used in the food industry to improve flavor and shelf life, but the FDA has announced it will be phased out of the U.S. food supply because it is damaging to health.

Trans fat and disease risk

This increased risk is significant. A 2006 meta-analysis found that a 2% increase in trans fat intake is associated with a 23% increase in cardiovascular disease risk. Cutting commercial trans fat intake from 2.1% of daily energy intake to 1.1% could potentially prevent 72,000 cardiovascular deaths. A drop to 0.1% of daily energy intake could potentially prevent 228,000 cardiovascular deaths every year in the U.S.

While the evidence on ruminant-produced trans fat isn’t conclusive regarding potential heart health benefits (especially at the doses commonly ingested), a recent meta-analysis points to no detrimental impact on cardiovascular disease markers.

Even though the FDA has recognized the negative health effects of trans fat and is taking steps to remove it, trans fat is still prevalent in our food. While the American Dietetic Association (ADA) recommends no more than 1% of your daily calories come from trans fat, unclear nutrition labels can sneak a lot of trans fat onto your plate. If a nutrition label claims the product contains “partially hydrogenated” fat or “zero grams of trans fat,” that doesn’t mean there is no trans fat in the product. This is because the FDA previously allowed products to be labeled with zero grams of trans fat as long as the product had less than 0.5 grams. Multiple servings of “zero grams of trans fat” food can result in much more ingested trans fat than the ADA recommends.

Trans fat consumption is a significant contributor to cardiovascular disease. The FDA has long recognized this and finally decided to gradually eliminate it from our food system by 2018. Until then, any industrially produced trans fats still present in our food system should be avoided, though this can be quite difficult due to confusing and misleading nutritional labels.

To explore the potentially healthy side of natural trans fats, click here to see our entry on CLA.

Posted by KamalPatel on Jun 30, 2015

We all know that marijuana is a popular recreational drug- and that it’s also got a variety of medicinal uses, including reducing nausea and boosting appetite. But what, exactly is marijuana - and how does it affect the appetite and digestive system?

The answer to that first question is pretty simple, so let’s start with that. The term ‘marijuana’ refers to several plants in the cannabis genus, including sativa, indica, and ruderalis.

Doctors typically prescribe marijuana to treat inflammatory, gastrointestinal, and cognitive ailments. Marijuana is also frequently administered to cancer patients, since it helps ease the pain associated with chemotherapy while increasing the patient’s appetite. This is why marijuana is used in an effort to minimize weight loss, which could lead to further health complications.

As you can imagine, this increase in appetite is one of marijuana’s most well-known effects, you might refer to it as “the munchies”. In fact, historical sources confirm that people as early as 300 BCE knew that cannabis stimulates appetite, and noted how these cravings were for sweet and savory food. Let’s dig into why that happens.

How marijuana works

One of the main active ingredients in marijuana - a chemical compound known as tetrahydrocannabinol (THC) - is one of the main culprits responsible for “the munchies”. Once the marijuana is consumed (normally by smoking), THC activates a receptor called cannabinoid receptor type 1 (CB1), which helps increase appetite. CB1 is also involved with the receptor for ghrelin, a hormone that contributes to an increase in the sensation of hunger.

CB1 receptors appear in a variety of different areas of the body. In each of these areas, these CB1 receptors act in slightly different ways - and many of those effects help increase the desire to eat. CB1 receptors are found in all of the following areas:

  • The hypothalamus and rhombencephalon, two sections of the brain that help regulate food intake.
  • The basal ganglia, where they may help enhance the pleasure we get from eating.
  • The stomach and the small intestine, which also secrete ghrelin, speeding up digestion.
  • The limbic forebrain, where they may also influence the palatability of food.

Researchers have found that inhaling cannabis is also associated with lower levels of peptide tyrosine tyrosine (PYY), a peptide that contributes to appetite suppression. People who use marijuana recreationally tend to have increased levels of ghrelin and decreased levels of PYY, which may be one reason why their daily caloric intake tends to be greater.

Studies have also shown that a person’s method of THC consumption (oral capsules, smoke inhalation, or suppository) can influence their food choice, as well as their overall food consumption. For example, study participants who took a suppository consumed significantly more calories throughout the day than participants who took an oral capsule.

Recent research on CB1 has revealed that a synthetic form of THC (dronabinol) can activate a subset of neurons called proopiomelanocortin neurons (POMC). Though POMC are usually responsible for the feeling of fullness after a meal, these neurons can either release hormones that suppress hunger, or hormones that increase appetite. When CB1 is activated, these hormones prevent POMC from suppressing hunger, and enable it to start increasing your appetite.

Suppressing appetite through the CB1 receptor

Since activating the CB1 receptor contributes to an increase in appetite, blocking it has the opposite effect. Studies on individual cells show that blocking CB1 receptors significantly increases production of adiponectin, a hormone with anti-inflammatory effects and a negative correlation with obesity.

Researchers have also used compounds that can block the CB1 receptor - which are known as endocannabinoid antagonists - to treat obesity associated with eating disorders, which is characterized by compulsive binge eating or cravings for sweets and snacks. Animal studies show that rats given rimonabant, an endocannabinoid antagonist anti-obesity drug, experience weight loss and reduced levels of blood insulin.

Still, a lot more research is needed before we can start recommending these kinds of therapies to human patients. The CB1 drug Rimonabant, for example, failed to earn approval from the U.S. Food and Drug Administration (FDA) - and it’s no longer sold in Europe either, due to side effects associated with its use, which include severe depression and suicidal thoughts. Since CB1 receptors are found all throughout the body, it is difficult to pinpoint the cause of these side effects.

Future endocannabinoid antagonists, however, may play a role in treating obesity by blocking CB1 receptors, increasing adiponectin production, and reducing appetite.

Marijuana has been a part of our society longer than any one civilization, and researchers continue to paint a more complete picture of the compound with every passing year. Follow-up studies will not only need to investigate CB1’s effects throughout the body, but also the different ways THC functions when ingested in various ways. More research on marijuana may also lead to breakthroughs in the fight against obesity because of how effective manipulating hunger can be when it comes to controlling our daily caloric consumption.

However, we want to end this post with a reminder that marijuana use impacts more than just your appetite. If you’re curious, click here to learn more about the health benefits and risks of marijuana.

Posted by KamalPatel on Jun 23, 2015

The Examine.com page on Copper has been completed and our researchers have turned up some interesting results in the process.

The body needs dietary copper for cognitive development during infancy, as well as for optimal immune and bone health.

Too much copper, however, has been linked to Alzheimer’s disease progression. That doesn’t mean copper causes Alzheimer’s disease. Instead, some people appear to have a genetic predisposition to Alzheimer’s disease, which causes copper to harm neurons. Too much copper increases the damage done to neurons in these people.

Copper is abundant in developed countries, where it is found in most food, as well as drinking water. Copper deficiencies in otherwise healthy adults are unheard of, so supplementing copper to prevent a deficiency is not a good idea.

Although copper does play a structural role in the makeup of a potent antioxidant enzyme, Cu,Zn,-superoxide dismutase (SOD1), supplementing copper does not result in increased antioxidant defense.

Copper is an important part of a healthy diet, but supplementing copper may not provide much of a practical benefit. Though some research suggests copper may play a role in fighting heart disease, much more research is needed to confirm this hypothesis. Since too much copper can have negative health effects for older people, copper is not recommended for supplementation at this time.

Posted by KamalPatel on Jun 16, 2015

Every month, it seems like there's always a new diet drink or artificial sweetener popping up in our grocery aisles, claiming that it not only offers all the benefits of its nonfat predecessors, but it also comes with none of the downsides. Meanwhile, it’s hard to avoid the reports that claim to link various artificial sweeteners to weight gain, cancer, and other dangerous effects. So how can you separate fact from fiction?

A selection of sweeteners

The most common non-caloric artificial sweeteners (NAS) are substances with a very intense sweet taste. They’re used in small amounts to replace the sweetness of a much higher amount of sugar, or of other derivative substances.

You’ll probably recognize at least some of the following names of common artificial sweeteners:

But are any of these sweeteners really any better than the others --or perhaps, riskier? Let’s break down what the actual research has to say.

Health Benefits

The main benefit of artificial sweeteners (or non-nutritive sweeteners) is to provide a zero-calorie alternative to foods and beverages, while still giving them a sweet taste. Replacing refined sugar with artificial sweeteners in your own diet can be an effective way to lower your calorie intake - which can allow you to bring in some healthier higher-calorie foods instead. Some studies have found that this kind of adjustment can help obesity, diabetes mellitus, and similar problems.

Health Issues and Safety

The truth is that only a few artificial sweeteners have been studied in-depth: aspartame, sucralose, acesulfame-K and saccharin. The majority of existing clinical and lab data only cover these sweeteners.

1. Aspartame

The FDA first approved aspartame in 1974, in light of a large amount of evidence - from labs and clinics in the United States, as well as from more than 90 other countries around the world - that demonstrated its safety for human consumption. So why did people get so paranoid about aspartame? Most likely because of a few studies on rodents, which have found that exposure to aspartame is associated with various cancers in rats and mice.

However, experiments have shown that the doses of aspartame required to pose danger to humans are far larger than what any normal person could consume in a day. The FDA has set the acceptable daily intake (ADI) for aspartame at 50 mg/kg of bodyweight - the equivalent of a whopping 18 to 19 cans of diet soda.

Rodent studies have shown a dose-dependent increase in lymphomas, leukemias, and transitional renal cell tumors in rats and mice who received doses of aspartame lower than the ADI - but while rodents and humans do share some metabolic similarities, the mechanisms our bodies use to process aspartame and other relevant compounds are different from those in rats. This fact has led most researchers to conclude that a comparison between rodent and human effects would be invalid in the case of aspartame.

For people born with phenylketonuria (PKU), a rare inherited disease, aspartame can help create dangerously high levels of the naturally occurring essential amino acid phenylalanine - and there’s also some evidence pointing to a possible relationship between aspartame and migraine headaches. For most people, though, aspartame has always been perfectly safe at reasonable doses.

2. Acesulfame-K

The human body doesn’t metabolize Ace-k at all, so it provides no calories - but it’s 200 times sweeter than table sugar. One breakdown product of ace-k is a chemical known as acetoacetamide, which is known to be toxic if consumed in very large doses - but the amounts of acetoacetamide found in spoonfuls of Ace-k are far below dangerous levels. Still, although plenty of research has found that Ace-k is safe for animals, human studies are still rare.

3. Sucralose

Although sucralose is made from sugar, the human body doesn’t recognize it as sugar, so it’s not metabolized - which means it provides no calories. Most of the sucralose we consume is excreted as waste - while another 11% to 27% of it gets absorbed into the bloodstream through the gastrointestinal tract, removed from the blood by the kidneys, and eliminated through our urine.

The acceptable daily intake (ADI) for sucralose is 5 mg/kg bodyweight per day, but the typical person’s estimated daily intake is a significantly lower 1.6 mg/kg per day. Human trials haven’t reported any significant dangerous effects for sucralose at all - but similarly to studies on aspartame, some research has found a relationship between sucralose intake and migraine headaches.

4. Saccharin

Among all the artificial sweeteners listed here, saccharine is the only one that deserves a stain on its reputation. The FDA tried to ban saccharin in 1977, in the wake of a series of animal studies that found close linkages between saccharin intake and the development of cancer in rodents. And while no study has ever shown a clear causal relationship between saccharin consumption and health risks in humans at normal doses, some studies do show a correlation between saccharine consumption and human cancer incidence.

More recently, researchers have found that saccharine can impair glucose metabolism in rodents. This has become a fairly controversial idea, though, and it’s probably the origin for the bad rap that all artificial sweeteners tend to catch.

A recent study by Suez et al. pooled evidence from animal studies to demonstrate several dangerous effects of saccharine - and those same authors also performed a study in which they administered high doses of saccharin to human subjects, then transplanted feces from two human subjects to two rodents. This transplant, the researchers found, caused some damage to the rats’ intestinal microbes, which in turn lowered their tolerance for glucose.

The news media grabbed the results of this single study and blew them out of all proportion to the facts, spawning outrageous headlines like “Diet Soda Causes Diabetes.” The truth is, a lot more research is needed to determine the effects of saccharin (and most other artificial sweeteners) on the human microbiome in vivo. For now, there’s no compelling evidence to suggest that normal doses of saccharin pose any harm to humans.

Aside from that, saccharin is nearly non-existent in today’s diet foods and beverages. Aspartame and sucralose are found all over the place - but saccharin is only found in Tab and a few other fountain drinks, and in the sweetener Sweet’N Low, where it’s present in tiny amounts. In order to match the dose that Suez et al. found to be dangerous for humans, you’d have to drink four cans of Tab, ten packets of Sweet’N Low, or fifty servings of a saccharin-containing fountain drink. So on the whole, even saccharine is a pretty low-risk sweetener.

Weight Management and Diet

What about the effects of artificial sweeteners on your weight-loss plans? Most short-term and long-term studies on humans have found that consuming artificial sweeteners doesn’t seem to decrease dieters’ energy intake - and randomized trials have found that people who use these sweeteners in place of refined sugar can successfully reduce both their weight and their body fat. Only been a few studies have examined the overall effects of artificial sweeteners on body weight - but every study has found reductions in weight and body fat in groups of people who use artificial sweeteners, as opposed to normal calorically dense ones.

So, should you be concerned? Maybe. Generally speaking, the only people who should be worried about artificial sweetener intake are children, pregnant women, nursing mothers, and those prone to seizures, headaches or migraines. If you don’t fall into one of those groups, then you probably shouldn’t be worried about opting for diet soda instead of regular soda.

However, if you’re concerned about high blood pressure, there’s another reason to worry about that can of pop.

Posted by KamalPatel on Jun 9, 2015

Our eighth issue of the Examine.com Research Digest is finally out and this month we dive into gut health, vitamin K2 and yet another study on meal-timing.

June’s sneak peek breaks down a recent trial on probiotics and how it might improve cognitive reactivity.

Click here to see this month's complete line up.

Serious about nutrition? Subscribe now for the latest in nutrition research.

Posted by Sol on Jun 2, 2015

With our recent hiring call, we thought it would be useful to our readers and fans to understand exactly how we hire. With over 500 applicants, it's important we do it right.

While we are not an organization that puts a lot of weight into a resume, the resume and cover letter is important to us as it lets us understand the background a person is coming from. It is most important to us that we work with people who are well-rounded individuals and have relevant experience in the field. It's easy to say "I'm passionate about nutrition," but experience helps you understand and appreciate the nuances and nitty gritty that self-interest does not always expose.

Once we have been able to discern who the potential candidates are, we then operate on a very simple premise: show us your abilities.

We are not interested in how well someone interviews, or how amazing their resume looks, or the full sequence of credentials found after their name. We care about the work you can do.

For a copyeditor, we may give them something a researcher has recently written that needs to be cleaned up and made reader-friendly. For a researcher, we'll send over a study and say "analyze this study." A subject matter expert would be given a few documents and say "make notes on anything that stands out."

None of what we send over is written up specifically for them. We always assign actual work. So if we gave a copyeditor something to clean up, it's something we recently completed and have also cleaned up (we just have not published it). So not only is it real work, it lets us compare and contrast with the work we're already producing.

One important step we do take is that there is always a middlewoman (more specifically, Carolyn, our Director of Ops) between the applicants and the rest of our team. Carolyn then anonymizes all of the applicants so that our team that reviews the work has no clue who they are reviewing. This is our way of ensuring that we remain as unbiased as possible - no consideration for friendship, for gender, for race, for name, for anything.

We care for just the work.

Once we have received completed work, an internal team goes over the work, and judges it based on a variety of criteria, including depth, nuance, clarity, brevity, and more. Comments and concerns are also included by each team member. This information is then passed onto Carolyn and Kamal (our Director), to make the call on which applicants are still under consideration.

It is through this iterative process that we are able to select the best candidates and make sure that Examine.com continues to deliver the highest quality analysis for everyone!