The major update this week is baking soda, more formally known as Sodium Bicarbonate. In a very general sense, it is comparable to Beta-Alanine in regards to both mechanisms and overall effect size, but outperforms it on a few parameters:

• On price and availability; baking soda is available everywhere
• Can reduce the pH in the blood, whereas beta-alanine only reduces intramuscular pH

However, baking soda is worse than beta-alanine on a few parameters as well:

• Simply ingesting baking soda without much thought would result in a very high dietary sodium load (above 5 g). Although this can be attenuated greatly by taking the lowest effective dose and cutting some of the baking soda with potassium bicarbonate, there will always be a sodium load that needs to be factored into the diet and will contraindicate baking soda supplementation for those with salt-sensitive hypertension
• There are well-known intestinal side effects if too much baking soda is taken rapidly. Although there does appear to be a dosing protocol to greatly minimize side effects, this is somewhat inconvenient and requires good timing and adherence to the protocol
• In general, there are many more precautions that need to be taken (from both a health and an intestinal perspective) when using bicarbonate supplementation than with beta-alanine

Finally, the limited studies into bicarbonate and beta-alanine as a combination do not find any additive benefits. If one is already taking beta-alanine, there is likely no need to add in bicarbonate.

Overall, sodium bicarbonate does appear to work, and can potentially be a cheap and widely available ergogenic supplement; yet it requires caution in approaching supplementation.

Beyond bicarbonate, we tackle the Branched Chain Amino Acids, and establish an individual page for all three of them: Leucine, Isoleucine, and Valine. Most information is interspersed within the pages (we attempted to collect it all on the BCAA page, and then opted for a cleaner read on the individual amino acid pages).

Leucine seems to be the standard muscle-building agent, and consuming leucine (either via food, BCAAs, or individual leucine supplementation) does promote muscle protein synthesis; this appears to be more significant in persons with lower dietary protein intake.

Isoleucine seems to be a hypoglycemic agent. It is not as effective as leucine at stimulating muscle protein synthesis, but causes dose-dependent increases in glucose uptake in skeletal muscle. The conversion of glucose to energy is enhanced, but glycogen synthesis is not; thus isoleucine may make a nice pre-workout when taken with carbohydrates. It works via a relatively novel mechanism (shared by leucine, but not by many other supplements) and might work nicely with other hypoglycemic agents such as AMPK activators (like berberine) or muscle contraction itself.

Valine, due to being quite understudied, is actually very unremarkable and does not appear to have any known unique properties.

Finally, the metabolite of leucine known as HMB (beta-hydroxy-methyl-butyrate) has been updated. HMB is less effective than leucine at promoting muscle protein synthesis, yet much more potent at inhibiting muscle protein breakdown (on a gram-per-gram basis). However, the human studies using HMB are all structured to measure the muscle-protein-synthesis effects of HMB, and due to this they are quite lackluster in their results. Preliminary evidence in clinical settings (not in athletes) does suggest a relevant anti-catabolic effect, but although it should work, this is not yet demonstrated in the population most likely to supplement HMB.

HMB is technically a potent anti-catabolic but requires further testing in athletes to confirm.

This study investigates the molecule Phosphatidylcholine. The study was conducted by having subjects eat two eggs, each containing 500mg Choline, alongside 250mg of phosphatidylcholine, which was radiolabeled. Phosphatidylcholine (PC) is a phospholipid (“lecithin” is a term sometimes used to refer to all dietary phospholipids, and will be used in this blog post for simplicity) which contains choline. By using labeled PC, the study’s authors were able to confirm that dietary choline acutely increased serum TMAO, and that this was dependent on intestinal microflora (similar to what occurred with carnitine). It should also be noted that both choline and carnitine are trimethylamine compounds.

Contrary to media reports, there is no molecular link between egg consumption and TMAO in this study. The radiolabeled phosphatidylcholine was consumed via a gelatin capsule alongside two (nonlabeled) eggs, which contained free choline. However, the PC increased serum TMAO dependent on intestinal bacteria, and it is definitely plausible (and likely) that eggs can increase TMAO via the choline content; this cannot be concluded right now though.

Similarly to the carnitine study, this experiment confirmed a correlation between higher TMAO and cardiovascular risk with a cohort study design (4007 persons undergoing coronary angiography) with an adjusted hazard ratio of 1.30 and 95% CI of 1.20 to 1.41 (a weak correlation, but a positive one nonetheless).

There was a higher hazard ratio when looking only at the subset of “death from cardiovascular disease,” which was an RR of 3.37 with a 95% CI, 2.39 to 4.75; this is somewhat notable.

This study also confirmed a correlation between TMAO and cardiovascular disease risk, so it appears that TMAO may be a useful biomarker in the future for cardiovascular disease risk. Whether TMAO is increased by dietary factors or other factors, it appears to be associated with an increased risk for heart disease.

That was basically the study. This study can be used to support the correlation between TMAO and cardiovascular disease, and similar to the previous carnitine study, this was confirmed at least acutely in humans. This study can also be used to further support the link between the microbe capable of choline -> TMAO conversion as a possibly causative link in the pathology of CVD, so identifying this microbe might be therapeutic or preventative in regards to CVD in the future (via modulating the increase of TMAO from the diet).

However, this study is not sufficient evidence to blame eggs for causing CVD. This is especially true when we factor in a variety of studies that explicitly found that egg consumption was not associated with an increase in cardiovascular disease^[2][3][4]. It can lend credence to the theory that choline increases atherosclerosis (as there is a plausible mechanism in humans), but is not proof of it; a few factors (having a mixed diet, not having the microbe, other negative regulators of atherosclerosis such as exercise) could make the observations seen here in a clinical setting irrelevant in a practical setting.

More likely, the bacteria that helps convert to TMAO uses the trimethylamine structure (which both choline and carnitine are) to make TMAO. This bacteria (currently unidentified) is the causative agent here, and merely uses sources of trimethylamines (eggs being a source of choline via PC) to do its job.

While one can directly blame eggs for the increase in TMAO, it would be improper to blame egg consumption for increased TMAO (which is correlated with an increased risk for cardiovascular disease). Any blame would better be directed towards the intestinal metabolism and the bacteria that helps convert to TMAO.

Related: are eggs healthy?

At the end of the day, we care about answering one question: What does a supplement do?

And today we finally solve that problem. We've replaced the confusing and cumbersome "Human Trials Database" with a "Human Effect Matrix."

For every supplement in our database, a handy table will tell you what effect each supplement has and how noticeable that effect is.

Does Supplement X help with Y? Now you'll know.

Creatine? It has a minor effect in increasing your testosterone, but a strong effect in increasing your power output. What about fish oil? It has actually has a notable effect in decreasing depression!

Best of all, the Human Effect Matrix isn't on the supplement pages only. They are also on the effect pages themselves. Want to know which supplements impact inflammation? Done! Do any supplements help you add muscle? Now you know. (Spoiler: they all have, at most, a minor effect).

What we've done is removed all the mysticism, hyperbole, and marketing-speak used to talk about supplements. It's all tabulated and organized for your perusal, and it's all backed with citations with human-studies.

To get you going, here are a few popular and a few interesting supplements:

• Creatine
• Vitamin D
• Fish Oil
• Berberine
• Spirulina

The page on MSM as well as glucosamine (where sulfate works, but hydrochloride doesn't) having similar effect size and variability in benefits seem to suggest that the joint health is coming from sulfur provision rather than the vessel by which sulfur is provided. In this case, a high dietary protein intake (via methionine and cysteine) or supplemental N-Acetylcysteine would also be similarly effective. Future trials need to investigate effects of these supplements in persons with or without relative sulfur deficiencies.

Rhodiola Rosea is an Adaptogen compound with the main bioactive of hydroxytyrosol and its glycoside (salidroside); it appears to be highly effective for combating neural fatigue and reducing the side-effects of fatigue (reduction in cognition, increase in depressive or stress symptoms) although it currently does not have much support for improving physical fatigue associated with exercise and is mostly unexplored in chronic fatigue syndrome. Rhodiola appears to be an effective supplement for work-related 'burnout'.

There are other health benefits associated with rhodiola, and alongside Panax Ginseng rhodiola is an adaptogen that is used in research often to merely see the effects of this 'adaptogen' class. Due to this, some evidence links rhodiola to promoting longevity independent of caloric restriction but this requires mammalian evidence.

Guarana is an energy producing seed powder that is the highest naturally occurring source of Caffeine. Guarana is somewhat unique in the sense that 90mg of the seed (conferring a level of caffeine that is commonly seen as inactive) appears to promote cognition. It is not known what molecule is causing this as it has not yet been identified, but something in guarana appears to either inherently promote cognition (perhaps secondary to an anti-fatigue effect) or work synergistically with caffeine.

Despite the popularity of guarana in energy drinks, there is a surprising lack of research available in English, with most being hidden behind language barriers (Spanish) and not catalogued on main databases such as Pubmed.

Olive leaf extract is a supplement with a high concentration of tyrosol-like molecules, and appears to be a very potent antioxidant following oral ingestion of low doses that seems to protect LDL cholesterol from oxidation. There is a large body of evidence on this topic using virgin olive oil against processed (processing destroys the phenolics) where even doses as low as 9mg appear effective.

Olive leaf extract appears to be very promising for perhaps being included in combination supplements (since it is active at a low concentration) and the Examine page can be used as evidence to the benefits of virgin or cold-pressed Olive Oil over processed oil as there does appear to be significant health differences between them due to the olive leaf phenolics.

Salvia hispanica (Chia) is a grain/seed that has traditionally been used as a meal replacement and energy promoting agent. Overall, there is currently no evidence to support chia as being remarkable in any capacity. There is insufficient data on the phytonutrients in chia (so no conclusions can be made there) and human evidence so far is just not remarkable. Anecdotally, however, chia appears to be as nice for promoting good bowel movements as psyllium husk which may be a good use for it.

Krill Oil is a form of Fish Oil fatty acids where, rather than being triglycerides, the fatty acids are present in phospholipid forms (most prominent one being Phosphatidylcholine). Krill oil is better absorbed than fish oil on a per gram basis and thus requires a lower dose (if using the dosing protocols of fish oil from other fish) and supplementation is essentially combination supplement of both fish oil and phosphatidylcholine; the Astaxanthin content of krill oil has not yet been demonstrated to contribute to the benefits.

Currently, the evidence in support of krill oil is very remarkable in the magnitude of benefit (the independent study in hyperlipidemics noting a 50% increase in HDL-C) and although it is independent of any disclosed financial support all studies seem to use 'Neptune Krill Oil' and are a tad too promising. Consider the evidence preliminary, and an independent systemic review would be very valuable in the near future to assess if krill oil is 'just fish oil and PC' or something more.

And three other Ayurveda based brain boosting herbs: Jatamansi, Evolvulus alsinoides, and Convolvulus pluricaulis. The latter two are two of the four herbs referred to as 'Shankhapushpi' (alongside Clitoria Ternatea and Canscora decussata) while the former herb is simply referred to as jatamansi. All three herbs are preliminary in their evidence with no human studies, but animal studies suggest that they can increase learning and memory in otherwise healthy young rodents with potency similar to the reference drug (Piracetam) or, in the case of Jatamansi, may be exceeding Piracetam. Mechanisms are not known for these herbs, but the general phenotype of rodents following ingestion seems to be similar to Bacopa Monnieri (in regards to anxiolysis, antidepression, learning enhancement, neuroprotection, and adaptogenic effects).

TMAO is thought to be atherogenic (plaque causing) because it is associated with cardiovascular disease (i.e., people who get heart attacks tend to have more TMAO in their blood). This study itself established a correlation (n=2595 cohort) between cardiovascular disease and greater blood concentrations of TMAO.

TMAO's molecular structure is common to both carnitine and Choline, and thus it is thought they can bioconvert in the body. TMAO is thought to contribute to atherosclerosis by promoting cholesterol influx into macrophages, which then promotes foam cell formation (and then the foam cells themselves become plaque); this was confirmed in ApoE^-/- mice (genetically modified mice used for cholesterol research purposes) in this study, and appeared to influence macrophages derived from wild-type mice as well. This mechanism is plausible.

The study above noted that following consumption of l-carnitine (180mg via sirloin and 250mg via radiolabelled capsules), TMAO was confirmed in both the blood and urine. The role of intestinal microflora was confirmed when participants were put on antibiotics (to suppress the microflora), which abolished diet-induced TMAO increases. Furthermore, this increase was detected in omnivores but not long term (more than 5 years) vegetarians and vegans, and seemed to be related to a higher gut population of Prevotella bacteria.

Finally, the researchers conducted a study in APoE^-/- mice. The mice fed carnitine had roughly double the plaque buildup vs mice that were not fed carnitine. This was again abolished with antibiotic treatment (to destroy the gut:TMAO link). It should be noted that APoE^-/- mice are genetically modified to exacerbate any bad cholesterol effects (for research purposes).

Note: The previous version of this article made note of '1.3% carnitine in the diet' which was a misreading from the paper. Carnitine was supplemented at 1.3% of the drinking water. Quantification of carnitine ingested is difficult, but assuming an intake of 5mL of water daily (somewhat in the ballpark of mouse studies) this would translate to 65mg carnitine in mice (and assuming 25g in weight, which is in the ballpark for a 10 week old female mouse, 2,600mg/kg) and a preliminary human estimate of 208mg/kg. This oral dose is not practically achieved via supplementation or diet despite what the first draft stated; we apologize for any confusion

Overall, what can we conclude from this study?

• There is a correlation between higher TMAO in serum and cardiovascular disease risk in humans.
• There appears to be microbial fermentation of dietary carnitine into TMAO in non-vegetarian humans.
• TMAO in serum from dietary carnitine causes atherosclerosis in APoE^-/- mice.

What cannot be concluded from this study?

• TMAO in humans causes heart disease. ApoE^-/- mice are used since it is easy to research pro-atherogenic cholesterol metabolism, but these are mice with a specific genetic fault. This research would have to be replicated in regular mice (and then in humans). Additionally, the human correlational research does suggest there is a link but cannot state that it is a causative link, and past research on Choline does suggest that TMAO is fairly rapidly excreted via the kidneys (suggesting some effects that are differential dependent on species).
• Carnitine causes heart disease, as the link between TMAO and heart disease is not fully established in humans.
• TMAO is bad. To nip this in the bud, most molecules have good and bad associated with them (good example: Cortisol) and it would be improper to conclude that TMAO must be avoided at all cost. To reiterate as well, the correlation between TMAO and cardiovascular disease could very well be a biomarker of some other lifestyle habits.

What can plausibly be concluded, but requires future research to confirm?

• Carnitine could contribute to heart disease via pro-inflammatory mechanisms, and this pro-atherogenic effect can likely be negated by other nutraceuticals (including statin drugs such as red yeast extract or other hypocholesterolemic compounds like Berberine).
• Probiotic supplementation could modulate heart disease risk via a TMAO link, but this assumes that the TMAO link is actually relevant in humans.

TL;DR?

The study found that in genetically modified mice, a high (but not impossible) dosage of l-carnitine did double plaque buildup. This may or may not be related to TMAO, we cannot say. This may or may not happen in humans, we cannot say. Overall? It's just preliminary research that should only interest other researchers, not the layperson.

At this time, restricting your carnitine consumption is not a prudent response for most people.

Want to learn more? See if red meat causes cancer.

Echinacea has been added as somewhat of a reference for being an 'anti-cold herb.' Echinacea is technically better than placebo for reducing both sickness frequency (in those who are frequently sick) and the duration of sickness, if taken at the first signs of sickness. Echinacea does not appear to do anything to the symptoms themselves.

Overall echinacea appears to be noteworthy, but at the same time the unreliability of it reduces a lot of faith one can put into the supplement. It is likely that some of the alkylamides are more effective than others ('alkylamide' refers to the collection of more than a dozen molecules which appear to be active) and future research may require isolating these alkylamides and seeing which one does what.

So if echinacea's effectiveness is weak, do we have something that shows promise? Kan Jang capsules (a Traditional Chinese Medicine consisting of both andrographis and eleuthero) have preliminary evidence to support a strong reduction in symptoms, mostly affecting the nose, ears, and throat and also reducing sickness length. Andrographic paniculata was added a few weeks back and appears to be the active component, and we have added the other component known as Eleutherococcus senticosus (formerly known as Siberian ginseng and totally unrelated to Panax Ginseng).

Eleuthero (as its common name) does not appear to be very effective for physical exercise performance improvement, although it may possess Adaptogen-like effects and anti-fatigue effects. There are some cognitive protective effects in rats that, while not amazing, are better than other dietary supplement and perhaps deserve some more investigation.

Unrelated to both immunity supplements above is Stevia, the natural sweetener. This one is interesting as it is both bioactive (can exert benefits to the body at fairly normal doses) and is theoretically possible to overdose on stevia. An overdose of stevia is likely to negatively influence fertility before anything else, and although controlled usage of stevia is unlikely to have such negative effects, the dose of stevia that is required to induce negative effects is wholly possible (probably around 8g a day, which is still a fair bit). Other sweeteners (aspartame and sucralose) are mostly inactive until extremely high levels of dosage, which allows a great safety buffer. This appears to be absent with stevia.

Finally, our major update was to Coenzyme Q10. It is highly recommended to supplement with CoQ10 if you are using statin drugs or after a myocardial infarction, and preliminary evidence suggest very effective symptom reduction for fibromyalgia. There are a lot of other disease states that also have lower CoQ10 levels, but have less evidence for their usage. Due to the interaction with heart health, it has been added to our heart health stack.

Beyond select disease states where CoQ10 is astoundingly important, CoQ10 is mostly just a moderately potent cardioprotective agent. It can reduce artherosclerosis somewhat (somewhat novel at the level of the lipoprotein, not novel at all at the level of the blood vessel) and secondary to that may reduce Blood Pressure, but is a bit unreliable in doing so.

Due to the high safety threshold with CoQ10, supplementation is either beneficial or a waste and is likely never adverse or dangerous. Finances may be the determinant if a healthy person wants to use CoQ10 supplementation, as many of the benefits that occur without a disease state may be present but too small to notice.

In terms of traffic and reach, we continue to grow. We are on pace to easily crack 200,000 visitors this month. Those visitors will spend over two minutes each on our site, and will generate roughly 450,000 pageviews! We also have over 7000 Facebook likes across our site (not including our fan page), and Claire Yates was our 1000th follower on twitter (perfect timing, she just followed us).

On top of that, we now feature over 15,000 references. Our Human Trials database now has over 1500 studies, of which over 1000 are double blind. The Human Trials database is also getting a significant update, but that's for another day.

We’ve always focused on one goal – to be a reference site. We’ve had no desire to be in the content generation game, and other than tackling hot topics via our blog, we’ve kept to our original mission.

We do need help. While 200,000/month may seem a lot, it’s not to us. We want 10x that. The reality is that the content matter on Examine.com can be dry – we don’t engage in sensationalism and we don’t engage in top 10 lists to drive us traffic. We aren’t afraid of controversy, but by the time we get done covering nuances on any topic, we don’t really generate a lot of anger. We do get an email a day saying how useful Examine.com was, and we love those emails.

So how can you help? Spread the word. Share us on Facebook, tweet about how awesome we are (it's true!), and if you have a blog or site, link to us. We're doing our best to inform the public, but we cannot do it without you.

Have to be honest - we are really excited about the upcoming year and seeing where it takes us (we do have a few things planned ...)

From what we can tell, the authors intentions are good hearted and prudent:

"I am reticent to provide exact brand names and instructions because I am not fully convinced of the diet's safety for a physiology different than mine"

"I was home for Christmas and saw an elderly family friend get admitted to the hospital after losing an unhealthy amount of weight. He was losing strength in one of his arms and found it very difficult to cook. I started wondering why something as simple and important as food was still so inefficient, given how streamlined and optimized other modern things are. I also had an incentive to live as cheaply as possible, and I yearned for the productivity benefit of being healthy. I'd been reading a lot of books on biology, and I started to think that it's probably all the same to our cells whether it gets nutrients from a powder or a carrot."

"The body is a complex machine. There are a lot of substances and chemicals required for it's optimal operation. However, it is also extremely robust. Many people aren't getting the recommended amount of any of these substances, but the body is able to compensate via complex regulatory systems. This hurts in the long run, though. In fact, turning food in to energy is the primary process that ages the body. By giving it only what it needs, and nothing it doesn't, I am optimistic about the long term effects. The short term effects are already clear."

The closing area of his article where he states:

So...I'll just ship you some of my batch. If you are willing to consume exclusively soylent, and get a CBC, chem panel, and lipid blood test before and after the week and share your results with me it's on the house. Bonus points for getting a psych evaluation before and after. The brain is an organ. I can ship it worldwide but it would be nice if you were in San Francisco so we can meet in person

Leads us to believe that this is more about self-experimentation than anything else. Thus, this seems to be more about good intentions than some kind of money-making scheme.

That being said, there are a few complications with the soylent formulation independent of the author's intentions:

• It is indeed simplistic. Simplifying can be good, but not when you start losing critical nuances. The author notes himself that "Many people aren't getting the recommended amount of any of these substances, but the body is able to compensate via complex regulatory systems. This hurts in the long run, though" in regards to the basic vitamins and minerals, but doesn't appear to have included compounds that following vitamin-like motifs in the body (what we call Pseudovitamin compounds) that are present in food but not soylent. Absolute exclusion of Choline, Creatine, or Nitrates may have similar adverse health effects.
• Fiber isn't digested, but that doesn't mean it is not needed. Especially with a liquid formulation, there needs to be some gel forming properties in the intestines to delay intestinal transit and allow maximal absorption. If the RDA of micronutrients is barely passable, at least do what you can to aid their absorption.
• All added non-vitamin compounds are horrendously underdosed. Personally, I never knew you could dose ginseng or ginkgo in the microgram range (the dose of ginseng used is currently about 1800-fold less than the lowest recommended dose of 90mg). There does not appear to be any good rationale for adding these compounds to the shake and in these doses, and it seems merely the most popular compounds were added regardless of their benefit to soylent.
• Cholesterol was omitted solely on the basis of not finding it necessary, an incorrect idea.
• Protein set at 50g a day is sufficient for survival (according to the RDA values) although it may not be optimal for sedentary persons and definitely is not optimal for active persons. Given the benefit of physical exercise for the purpose of 'biohacking' the body, it can be expected that many active persons would want to try such a shake. Due to this, the protein content needs to be reevaluated. It should be noted that the 50g minimum was calculated for a 137.5 lb person. We've covered how much protein you need to consume every day.
• Building on that, although the debate between having a 'complete' and 'incomplete' protein source does not matter too much at the higher range of intake (as you merely overconsume the insufficient amino acids) having plant based sources with low absorption percentages paired with a low dietary intake of protein is problematic. If protein intake is not increased, the source of protein should be switched to an animal based product like Whey Protein.
• The intake of Vitamin D, and perhaps Vitamin K, need to be reevaluated.
• Some trace elements, such as Boron, are not present.
• The fat source is exclusively from Olive Oil (mostly oleic acid) rather than being a mixed source. This needs to be revisited as no omega ratio appears to be investigated and the benefit of some other fatty acids (saturated ones in Coconut Oil or particularly gamma-linoleic acid or arachidonic acid) could be included rather than blindly using one fat source
• The carbohydrate source appears to be maltodextrin (similar to starch in the sense it is a long chain of glucose), although it appears unclear if it is solely maltodextrin. This is not an ideal carbohydrate source for infrequent consumption due to its rapid absorption and high GI (although this bullet is more pedantic than the others). Switching to an alternate carbohydrate source that is absorbed slower or possible one that (with dietary fiber or other indigestible components such as cellulose) has some benefit to intestinal microflora, would be prudent

Soylent really needs a reformulation if this takes off and more people decide to 'experiment' with themselves. Bumping the fiber up to 30g and adding some pseudovitamins would be a good start, but honestly the exclusion of food is something not many people should even consider. Once that happens, then it would likely just become another standard meal replacement shake.

The inherent problem with micromanaging foods down to their molecules is that there is a remarkable amount of molecules that you need to keep track of - the essential vitamins and minerals are not enough. Meal replacement shakes have, up until now, thrived as they replace one or two meals in the day and then mention that the consumer should 'eat a healthy well balanced meal' otherwise; absolute exclusion of food has never been recommended traditionally.

Soylent is not a new concept, although the idea of a meal replacement shake may be getting a second wind due to soylent. It needs a reformulation as the current one is very loosely based on what the RDA of micronutrients. It's quite deficient in several areas, and needs a much more thorough evaluation on its contents.

• Hemp Protein is a protein source derived from hempmeal (seeds after the oil has been extracted) and is mostly marketed for its 'balanced' fatty acid content of omega-3 and omega-6 fatty acids. It does appear to have a balanced profile, but the benefit of this in practical terms is doubtful due to the omega-3 source being alpha-linoleic acid rather than the Fish Oil omega-3s (EPA and DHA). Although there is no THC content in hemp protein like there is in Marijuana, there does appear to be some limited cannabinoid content; the practical relevance of these cannabinoids in hemp protein is currently not known (and it is unsure whether one can extrapolate data from marijuana onto hemp protein).

• Psyllium has been added and is the first in the new Dietary Fiber category page. Psyllium appears to be quite effective and proven as a 'bulk laxative' (laxative secondary to forming stool) and due to its low fermentability in the colon it resorbs a fair bit of water and possible gas to increase fecal mass, softness, and regularity. At least one study has noted decreases in flatulence associated with psyllium ingestion, and although there are health effects associated with psyllium (reduced serum glucose and cholesterol) these do not appear to be unique to psyllium and instead just common to any gel-forming fiber.

• Coconut Oil is a highly saturated source of medium chain triglycerides (MCTs), and appears to be somewhat effective as both a skin and hair moisturizing agent when directly applied (although the greasiness of coconut oil might need to be accounted for. When used as a part of a fat loss diet, there appears to be sufficient evidence to support the role of coconut oil in place of other fatty acids to increase the amount of fat lost over a period of time. The effect size is not remarkable, and sometimes the benefit is small enough that the difference is not significant; however, there does appear to be a beneficial effect of coconut oil MCTs on fat loss.

Of supplements that are not food products:

• Noopept was finally added, and based on limited evidence it does appear to be very similar in mechanism to Piracetam while requiring a much lower dose. Similar to piracetam, however, it does require more evidence in otherwise healthy subjects or animals to confirm a cognitive boosting effect

• Lavender was added to round out our Aromatherapy section, and actually appears to be a much more supported aroma than all the others. The aroma of lavender appears to be able to induce a reduction in anxiety and some limited sedation in numerous trials, and oral ingestion of lavender essential oil has some surprisingly robust evidence for it for reducing generalized anxiety disorder.

• 7-Keto DHEA was taken from the DHEA page and given its own entry due to the low hormonal activity of it. While 7-keto DHEA appears to be an anti-stress molecule and mitochondrial uncoupling agent, it requires more evidence and some larger studies to validate its usage in humans as the limited evidence right now is highly confounded with conflicts of interest or other nutrient inclusion. That being said, 7-keto DHEA may be able to increase the metabolic rate or at least attenuate the rate of decline during dieting.

• Nattokinase is a dietary enzyme found in some fermented soy products that is said to be cardioprotective by reducing fibrin binding and thus reducing the risk of thrombus formation. The evidence to support this claim is very limited and currently there isn't any evidence to support the usage of nattokinase over simply eating natto (which may actually be more effective, as nattokinase is but one of many enzymes created during the fermentation process)

The major update this week is:

Beet Root, but more precisely its active ingredient known as inorganic Nitrate. Nitrate is commonly ingested in vegetables and appears to also be endogenously produced in the body to a limited degree (almost meeting the nonlegitimate criteria of our Pseudovitamin category if it can be linked back to a disease state associated with a deficiency). Nitrate's metabolite, nitrite, circulates in the blood and is readily converted to Nitric Oxide with preferential conversion in deoxygenated areas of the blood and microcirculation.

It appears to quite reliably reduce blood pressure in persons with elevated blood pressure, and although blood pressure in healthy persons at rest in unaffected it seems to attenuate the rise in blood pressure during exercise.

Nitrate supplementation at or around 500mg reduces the oxygen cost of exercise and appears to be able to make mitochondria more efficiently work (secondary to nitric oxide). Due to this, usage of nitrate supplementation before exercise that is not maximal exertion but more glycolytic in nature (sprinting, prolonged resistance training upwards of 12 reps or so, crossfit) is able to prolong time to exhaustion, improve performance on time trials, and sometimes reduce the rate of perceived exertion. The effect size of nitrate is larger in these trials, nonexistent in maximal power output, and lesser in prolonged endurance exercise but appears to be greater than that of Beta-Alanine supplementation.

Finally, nitrate is converted to nitric oxide independently of the NOS enzyme (mediates conversion of L-Arginine into nitric oxide). This suggests that nitrate supplementation would be potentially additive with L-Arginine or L-Citrulline as they do not interfere with one another, but this requires some testing.

Nitrate appears to be a potential pseudovitamin compound with cardioprotective and performance enhancing effects, with the latter being slightly more effective than beta-alanine.

The vast majority of research on glucosamine is not for general joint health, but specifically for osteoarthritis. When looking at this claim in particular, glucosamine appears to be quite reliable in regards to its statistical significance (the likelihood that the observed results are due to intervention rather than chance) and due to that it appears to be unanimous in our human trials tables, which are based on statistical significance. The clinical significance (magnitude of benefit over placebo in practical terms) appears to be present, but is not as remarkable; it is comparable to acetominophen which is the reference drug for osteoarthritis, but both options are nowhere near curative.

There appears to be concern over publication bias for glucosamine, but two separate meta-analyses have failed to find such evidence of publication bias; the concern still seems to linger though, and is really only a concern due to the social popularity of glucosamine and how that is somehow this bias was avoiding the analysis thereof (funnel plots) that it could dwindle the already small clinical significance.

For the purposes of osteoarthritis, glucosamine seems to be a safe and effective option assuming you are not looking for a cure; acetominophen (Tylenol) appears to be just as good an option if you don't mind taking a daily NSAID drug though.

For athletes, there is some evidence to support the idea that the slowing of collagen degradation applies to healthy athletes and that this may be of benefit to high impact sports involving running or jumping. The evidence is much less for this claim relative to the osteoarthritis claim, but appears to be suggesting a protective effect.

Overall, glucosamine is remarkably safe (aside from possible flatulence) and there does not appear to be a large concern in regards to the link between glucosamine and insulin resistance; not enough appears in the blood following oral ingestion to reliably induce insulin resistance, and it is likely a non-concern.

The other addition to our database this update is the entire topic of Aromatherapy: bioactives that are lost to the air and find their way to the nose. Of these, Rose appears to be somewhat anxiety reducing when inhaled and Lemon Balm appears to be able to induce calmness and sedation (at the cost of alertness) when orally ingested. Patchouli is said to be calming but has no real evidence for this claim, although it may confer some anti-viral properties (that need to be investigated more) and clary sage also appears to have some possible uses but most studies using it are confounded with the inclusions of other herbs.

Aromatherapy is an interesting topic, but the body of evidence behind it is quite lackluster.

Lastly, we also announced our advisory board today. As Examine.com continues to grow (we are nearing 200,000 unique visitors/month), it becomes more important to have a clearly defined vision. Our advisory board will help us in our continued evolution.