Proven benefits of natural foods, products, and remedies

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Proven benefits of natural foods, products, and remedies

Postby BioWizard on October 22nd, 2015, 12:46 pm 

Prelim definitions:

Drug: a chemical substance that can interact with a biological component (ex a protein or enzyme) to elicit a biological effect

Drug target:
a biological component which, when engaged by a drug, elicits a biological effect

An example of a drug is aspirin (acetylsalicylic acid). The drug target of aspirin is cyclooxygenase, and enzyme that catalyzes a biochemical reaction that mediates inflammation and pain. https://en.wikipedia.org/wiki/Aspirin

Introduction:

For several decades now, the pharmaceutical industry has been obsessed with finding extremely selective drugs. i.e. Everybody wants to find molecules that specifically engage individual drug targets, without engaging any other biological targets in the cell/body. The motivation behind the one molecule -> one target approach is the toxicity and side effects that can result from a drug engaging targets that shouldn't be engaged. For example, if the drug that is designed to inhibit an enzyme that mediates inflammation (such as pain killers) but also inhibits an ion channel in heart muscles, it's going to have nasty cardiac side effects. So for the longest time, people thought that hyper-selective drugs would be the holy grail of modern medicine.

The challenge, however, was finding such molecules - given that the absolute majority of drug-like molecules tend to be promiscuous (engage multiple targets). Why? The simple answer: because if you throw thousands of different sized objects into a large container and shuffle them around, many of them are going to fit into one another by random chance. A more biochemically detailed answer goes something like this:

Proteins are three dimensional structures made from polymers of amino acids folded onto themselves. This creates a structure with bumps and clefts. On top of having surface topology, these structures also have electric charge and hydrogen bonding capabilities distributed over them (due to the presence of oxygen and nitrogen atoms in the amino acids). This is what allows proteins to be such efficient enzymes. This combination of physical and chemical topology allows proteins to have clefts where "substrate" molecules can come into and "fit". In simplest terms, these substrates fit for two reasons: 1- their geometric shape fits within the volume of the cleft, and 2- the chemical interactions on the inner surface of the cleft match up with the chemical surface of the substrate molecule (for example, each electrically charged point on the substrate molecule snugs up against an oppositely charged area inside the cleft, etc). And this kind of fitting holds a substrate molecule in place and makes it easier for the enzyme to "break" that molecule, which wouldn't otherwise be as readily to fall apart on its own. Think of how you wrap your fingers around a bar of chocolate in order to snap it in half. Once you break stuff up, you can rejoin them in a different conformation, or you can join them up with broken parts from other molecules. Basically, you got yourself some catalysis. And a lot of drugs work by going into, and occupying, the catalytic pockets of enzymatic proteins and preventing the substrates from entering to be reacted. The enzyme is said to be inhibited by the drug. If an enzyme is doing something that is mediating a disease condition, this enzyme is now your drug target, and a molecule that can inhibit the enzyme and reverse disease symptoms can be a drug.

So why is it so hard to find small molecules that would fit into the clefts of only specific enzymes? There is a large number of proteins, some with very different catalytic pockets, and some with very similar ones. Those with similar ones will tend to bind the same inhibitors. Also, a lot of proteins evolved from common ancestral genes. So even if they currently carry out different biochemical functions, they can still share a lot of their structural elements. Finally, many enzymes catalyze reactions for molecules that have similar structures. In order to fit those similar molecules, they need to have similar catalytic pocket topologies. The list goes on, but the point is that finding hyperselective drugs is difficult.

Nevertheless, the great minds of biochemistry, chemistry, and computational sciences came together, and eventually started creating those really selective molecules. The assumption was that such molecules would have the best efficacy and the least amount of side effects. Right? Wrong. A lot of these drugs failed clinical trials. They just weren’t efficacious enough. Reason? Biological systems are ROBUST. In other words, biology has evolved to be able to resist perturbation. Without that property, the slightest disturbance will throw a cell of balance and cause it to fall apart. So how do biological systems become robust? The same way any other system does, by creating a lot of failsafe mechanisms. One way to do that is by having a lot of redundancy. If you send three emails from three different accounts each time you want to contact somebody, chances are you will be less likely to fail reaching them. Similarly, if you block a single street in a city, you aren’t likely to cause as much traffic as you would if you block a strategically selected COLLECTION of streets. Why? Because road networks have lots of intersections which allow a very large number of ways to go from A to B. A single roadblock isn’t going to prevent that. However, if you insert several roadblocks such that you trap traffic trying to escape from the first roadblock, you can place the whole system in a gridlock.

So what does this all mean for drug discovery? Biology relies on signaling networks to get anything done. Cells have receptors on their surface and inside them that sense their chemical environment, and relay signals to their nucleus via robust biochemical networks. The nucleus interprets those signals and responds by altering its gene expression profile in a way that generates the proper ensemble of protein products that can execute the cell’s response to the chemical cue that it sensed. This means that taking one node out of these networks may have an effect, at first, but the cell will quickly learn to overcome it by ramping up two or three other pathways around it (a.k.a tolerance will be developed). Think of it as the cell sensing the block in one road, and opening up a couple others to allow the signal to go around it. This means that hyperselective drugs may have less side effects, yes, though at the cost of being entirely useless (long term).

One possible conclusion from this is that molecules that engage multiple targets can make better drugs, IF this promiscuity can be TUNED such that the multiples of targets engaged are acting together to create a real “jam” in the pathway(s) mediating a disease event, without influencing other healthy functions. Interestingly, retrospective studies done on most FDA approved drugs show that most of the engage multiple targets, and that these additional targets may be important for the efficacy of those drugs.

So now the question is how do we find drugs with “tuned promiscuity”? Well, that’s the challenge for the field at the moment, and a major research focus of mine. However, I didn’t want to specifically talk about that here. Rather, I wanted to use this as a segue to remind us of why natural products are important bioactives and why it is important to continue researching their medicinal properties. Naturally derived foods or extracts are often mixtures of tens or hundreds of bioactive molecules. This means that rather than having a single strong active ingredient, they have collections of ingredients that can be individually acting on a different targets, such that neither of them is singularly effective, but together can elicit significant therapeutic effects. And because we’re trying to achieve those effects with a collection of low potency compounds, it is less likely to get severe side effect or toxicity from any one of them. The idea is to find those mixtures that synergize on the good without adding up on the bad. This multi-mode of action also means that probability of developing tolerance is lower than when using an individual compound for the given indication.

Now granted, pharmaceutical drugs WORK, and that is why the industry will only continue to grow and become better at finding new, more effective, and safe drugs – I have no doubt about that. Add to that the fact that we may not find a cure or prophylactic for everything in nature. But I do believe that what does exist out there is worth learning about, whether in purified or (preferably) more native mixed forms. Clearly, pharmaceutical companies can't be motivated to conduct that research, because it’s not a viable model for them. But that doesn’t mean that academic researchers can’t investigate these things, given public support - I suppose. Even if they're not full on cures for anything, but can support and potentiate other treatments or help alleviate minor symptoms to promote a sense of well being, then there's no reason to not want to learn about them.

It's important to keep in mind that not all naturally derived products are safe, and that "natural" isn't necessarily better than "synthetic" or "processed".

About this thread:

I’ve been reading about a lot of folk treatments lately, some of which appear to have already been backed up by scientific studies. I would like to use this thread to share some of those natural remedies, what they have been traditionally used for, and what portions of those indications have been backed up by research. If anyone would like to jump in and post links, articles, questions, or add anything to the thread, please feel free and welcome to do so. We can use this as a forum to discuss folk claims and try to separate truth from fiction (including the natural supplement scam industry) given what is known so far.
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Re: Health benefits of natural foods, products, and remedies

Postby Braininvat on October 22nd, 2015, 1:58 pm 

http://www.bloodpressureuk.org/mediacen ... odpressure

This meta paper looks at the need for longer term studies. I think garlic is a good candidate for more research. It was a folk remedy that one of my grandmas used.
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Re: Health benefits of natural foods, products, and remedies

Postby BioWizard on October 22nd, 2015, 2:00 pm 

Garlic is definitely up there and one of the things I had in mind. Others include raw honey, black seed oil, fish oil and other omega-3s, cumin, and turmeric. Probably lots more but that's what came to mind right now.
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Re: Health benefits of natural foods, products, and remedies

Postby SciameriKen on October 22nd, 2015, 2:10 pm 

One of my research interest are micronutrients (e.g. reseveratrol) found in fruits and vegetables. Although for the most part the impacts of these are quickly dismissed in normal diet (something like 2000 glasses of wine must be drunk in order to have a pharmacologic dose of resveratrol!). However, I wonder if a diet based heavily in fruits and vegetables and the synergistic effects of such molecules can confer benefits.

That being said and jumping back to your example - I add this from wikipedia:

The therapeutic properties of willow tree bark have been known for at least 2,400 years, with Hippocrates prescribing it for headaches.[12] Salicylic acid, the active ingredient of aspirin, was first isolated from the bark of the willow tree in 1763 by Edward Stone of Wadham College, University of Oxford.[13] Felix Hoffmann, a chemist at Bayer, is credited with the synthesis of aspirin in 1897, though whether this was of his own initiative or under the direction of Arthur Eichengrün is controversial.[14][15] Aspirin is one of the most widely used medications in the world with an estimated 40,000 tonnes of it being consumed each year.[16] In countries where "Aspirin" is a registered trademark owned by Bayer, the generic term is acetylsalicylic acid (ASA).[17] It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[18]


Indeed this is a drug with roots in natural remedy. I think it is important to note that Aspirin is not salicylic acid in the sense that the acetyl moiety allows for the "blood thinning" impacts of aspirin(Through Cox inhibition), The Salicyclic moiety imparts dramatic anti-inflammatory properties (through NFkB inhibition), yet aspirin at this same does would be very dangerous and potentially deadly due to blood thinning. At least this was I learned at a conference a few years back from a lecture by Steven Sheldon. Just crazy how a couple itty bitty atoms can completely change everything!
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Re: Health benefits of natural foods, products, and remedies

Postby BioWizard on October 22nd, 2015, 2:19 pm 

SciameriKen » 22 Oct 2015 01:10 pm wrote:Indeed this is a drug with roots in natural remedy. I think it is important to note that Aspirin is not salicylic acid in the sense that the acetyl moiety allows for the "blood thinning" impacts of aspirin(Through Cox inhibition), The Salicyclic moiety imparts dramatic anti-inflammatory properties (through NFkB inhibition), yet aspirin at this same does would be very dangerous and potentially deadly due to blood thinning. At least this was I learned at a conference a few years back from a lecture by Steven Sheldon. Just crazy how a couple itty bitty atoms can completely change everything!


I'm not entirely sure what you're saying there SK :] The aceytyl moiety is what makes aspirin an irreversible inhibitor of COX (it gets transferred covalently from salicylate onto the enzyme). IIRC the blood thinning is caused by inhibition of prostaglandin synthesis (particularly the one that mediates platelet function).
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Re: Health benefits of natural foods, products, and remedies

Postby SciameriKen on October 22nd, 2015, 2:36 pm 

BioWizard » Thu Oct 22, 2015 6:19 pm wrote:
SciameriKen » 22 Oct 2015 01:10 pm wrote:Indeed this is a drug with roots in natural remedy. I think it is important to note that Aspirin is not salicylic acid in the sense that the acetyl moiety allows for the "blood thinning" impacts of aspirin(Through Cox inhibition), The Salicyclic moiety imparts dramatic anti-inflammatory properties (through NFkB inhibition), yet aspirin at this same does would be very dangerous and potentially deadly due to blood thinning. At least this was I learned at a conference a few years back from a lecture by Steven Sheldon. Just crazy how a couple itty bitty atoms can completely change everything!


I'm not entirely sure what you're saying there SK :] The aceytyl moiety is what makes aspirin an irreversible inhibitor of COX (it gets transferred covalently from salicylate onto the enzyme). IIRC the blood thinning is cause by inhibition of prostaglandin synthesis (particularly the one that mediates platelet function).


I wasn't sure of the mechanism of the COX inhibition - but what I am saying is salicylic acid by itself is an antagonist of NFkB signaling - but not at doses used with normal aspirin intake.
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Re: Health benefits of natural foods, products, and remedies

Postby BioWizard on October 22nd, 2015, 5:27 pm 

SciameriKen » 22 Oct 2015 01:36 pm wrote:I wasn't sure of the mechanism of the COX inhibition - but what I am saying is salicylic acid by itself is an antagonist of NFkB signaling - but not at doses used with normal aspirin intake.


Aspirin is a relatively low potency inhibitor of COX. I believe its IC50 is in the micromolar range. The reason it ends up having any efficacy at the typical doses is likely due to the fact that it's an irreversible inhibitor.

Since salicylic acid (which is aspirin minus the acetyl group) can bind COX but lacks the ability to inactivate it irreversibly through acetylation, what you end up with is a competitive inhibitor with horribly low potency. The study that I think you were referring to was arguing that acetyl salicylate rapidly hydrolyzes in the body into salicylic acid, therefore the mechanism of action of aspirin (which according to them is quickly converted to salicylic acid in the body) can't be through acetylation and inhibition of COX (since salicylic acid coming from an aspirin-grade dose can't do these things). So they're saying that aspirin (which according to them immediately becomes salicylic acid in the body) has to be inhibiting COX activity through some other mechanism. I wouldn't necessarily adopt such an extreme position, since the half-life of aspirin in plasma is 20 mins, not 0. So it's probably a mixture of several mechanisms (which goes back to the premise of the OP). I see the same story over and over, where we think drug X is working through mechanism A, and then we find that it's actually through mechanism A + B + C (whereby the combination is required for biological efficacy).

It's worth mentioning that there are two isoforms of cyclooxygenase: COX-1 and COX-2. COX-2 is the one primarily implicated in inflammation, while COX-1 is required for normal platelet, stomach, kidney, and other functions. That's why classic NSAIDs used to have nasty side effects on stomach function, blood coagulation, blood pressure, and so on. New generation NSAIDs have better selectivity for COX-2 (and much better potency).
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Re: Health benefits of natural foods, products, and remedies

Postby BioWizard on October 22nd, 2015, 5:52 pm 

Found this great study:

http://www.ncbi.nlm.nih.gov/pubmed/9187256 wrote:Sodium salicylate inhibits cyclo-oxygenase-2 activity independently of transcription factor (nuclear factor kappaB) activation: role of arachidonic acid.
Mitchell JA1, Saunders M, Barnes PJ, Newton R, Belvisi MG.
Author information
Abstract
Acetylsalicylic acid (aspirin) is the drug most commonly self-administered to reduce inflammation, swelling, and pain. The established mechanism of action of aspirin is inhibition of the enzyme cyclo-oxygenase (COX). Once taken, aspirin is rapidly deacetylated to form salicylic acid, which may account, at least in part, for the therapeutic actions of aspirin. However, where tested, salicylic acid has been found to be a relatively inactive inhibitor of COX activity in vitro, despite being an effective inhibitor of prostanoids formed at the site of inflammation in vivo. Recently, the identification of a cytokine-inducible isoform of COX, COX-2, has led to the suggestion that salicylate produces its anti-inflammatory actions by inhibiting COX-2 induction through actions on nuclear factor kappaB (NF-kappaB). We have used interleukin 1beta-induced COX-2 in human A549 cells to investigate the mechanism of action of salicylate on COX-2 activity. Sodium salicylate inhibited prostaglandin E2 release when added together with interleukin 1beta for 24 hr with an IC50 value of 5 microg/ml, an effect that was independent of NF-kappaB activation or COX-2 transcription or translation. Sodium salicylate acutely (30 min) also caused a concentration-dependent inhibition of COX-2 activity measured in the presence of 0, 1, or 10 microM exogenous arachidonic acid. In contrast, when exogenous arachidonic acid was increased to 30 microM, sodium salicylate was a very weak inhibitor of COX-2 activity with an IC50 of >100 microg/ml. Thus, sodium salicylate is an effective inhibitor of COX-2 activity at concentrations far below those required to inhibit NF-kappaB (20 mg/ml) activation and is easily displaced by arachidonic acid.


Basically they showed that salicylic acid indeed acts as a week competitive inhibitor of COX in intact cells, but for some reason not with the purified enzyme. They also showed that addition of arachidonic acid (the substrate of COX) decreases the inhibition, further demonstrating that salicylic acid is acting as a direct competitive inhibitor of COX activity.
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Re: Health benefits of natural foods, products, and remedies

Postby BioWizard on October 22nd, 2015, 5:54 pm 

To me, this suggests that either there are some other COX enzymes that we don't know about which also get inhibited by NSAIDs (although the study does provide some evidence that it's likely just COX-2) , or that purified COX fails to bind salicylic acid in vitro for whatever reason. NFkB does not seem to be directly relevant to the molecular mode/mechanism of action (MMOA). Either way, both aspirin and salicylic acid appear to indeed work by inhibiting cyclooxygenase activity (whoever is catalyzing it) on arachidonate.

That was a fun quick hunt. Thanks for that tangent Sciameriken.
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Re: Health benefits of natural foods, products, and remedies

Postby Watson on October 22nd, 2015, 5:57 pm 

Something Edgar Casey suggested was almonds, but I don't recall what the benefits were.

Also Cheyenne pepper, raw vinegar and tomatoes juice.
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Re: Health benefits of natural foods, products, and remedies

Postby BioWizard on October 22nd, 2015, 5:59 pm 

Watson » 22 Oct 2015 04:57 pm wrote:Something Edgar Casey suggested was almonds, but I don't recall what the benefits were.

Also Cheyenne pepper, raw vinegar and tomatoes juice.


Thanks Watson. If you have any studies that support the use of these foods, and for what particular indications, please post them. The idea is to keep this as evidence based as possible.
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Re: Health benefits of natural foods, products, and remedies

Postby weakmagneto on October 22nd, 2015, 8:23 pm 

What about medicines that haven't been studied? For example, First Nations of the Boreal Forest have used skunk medicine (oil from the spray) to cure persistent coughs, sore throats, etc. and bear grease to combat arthritis and other ills. As far as I could research, there are no studies that I could find about the benefits of these medicines.
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Re: Health benefits of natural foods, products, and remedies

Postby BioWizard on October 22nd, 2015, 8:36 pm 

weakmagneto » 22 Oct 2015 07:23 pm wrote:What about medicines that haven't been studied? For example, First Nations of the Boreal Forest have used skunk medicine (oil from the spray) to cure persistent coughs, sore throats, etc. and bear grease to combat arthritis and other ills. As far as I could research, there are no studies that I could find about the benefits of these medicines.


Hey WM. Unfortunately, we can only treat them as anecdotal for now, and therefore they are beyond the scope of this thread.

[edit: Changed the title to better reflect that]
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Re: Health benefits of natural foods, products, and remedies

Postby weakmagneto on October 22nd, 2015, 8:39 pm 

k Thanks. :)
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Re: Health benefits of natural foods, products, and remedies

Postby BioWizard on October 22nd, 2015, 8:40 pm 

weakmagneto, out of curiosity, what's bear grease?

https://en.m.wikipedia.org/wiki/Bear%27s_grease ?
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Re: Health benefits of natural foods, products, and remedies

Postby weakmagneto on October 22nd, 2015, 9:25 pm 

Bear grease is a hardened fat (much like lard) that is collected from roasted bear meat. It can also be rendered from frying bear fat. I am working on finding an appropriate link to include.
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Re: Proven benefits of natural foods, products, and remedies

Postby doogles on October 23rd, 2015, 6:41 am 

Wow Biowizard, I’m not sure where to start in this thread. I have a range of thoughts going through my head and may have some difficulty in getting a coherent response in place.

The first thing that crossed my mind is that almost every culture that ever existed on this planet appears to have had some belief in the value of local-growing plants to have beneficial remedial effects. Obviously this was anecdotal. The first point I would like to make is that TRIAL AND ERROR had to be the main means of identifying drugs with SPECIFIC actions, and the main yardstick of specificity would be that they had no serious side effects outside of their intended purpose.

For example, a preparation of the opium poppy would stop diarrhoea, ease pain and maybe reduce coughing fits. We now know that morphine derivatives antagonise a number (five or more) brain receptors. A preparation of Deadly Night Shade (Atropa belladonna) in moderate quantities would also ease colic pains associated with diarrhoea. A preparation of the bark of the Cinchona tree contains quinine which was in massive use by soldiers in WW!! to prevent malaria in soldiers who went to the Pacific area. We could pick those soldiers easily by their distinctly yellow skin in the 1940s. Aspirin, as a pain killer and prostaglandin inhibitor in the first stage of blood clotting has been mentioned: it was derived from willow bark and made a fortune for the Nicholas family. Cocaine from the coca leaf was used by South American indigenous people long before westerners for its ‘numbing’ effects and temporary improvement of vitality.

Don’t forget that Galen virtually established modern medicine when he attempted to standardise dried extracts from these plants as tinctures in the second century by mixing measured weights in known volumes of alcohol.

In the last century, we’ve discovered that Penicillium notatum contained a drug that would kill bacterial infections. And a whole new series of ‘natural’ antibiotics were discovered. A drug was found and isolated from the Devil’s Apple that would cure 84% of skin cancers without remission for ten years. In the 1950s a drug called reserpine was isolated from the Rauwalfia plant in India; it appeared to reduce blood pressure, but did not take off commercially.

Huge promise has been ascribed to the use of an extract from the berries of the Blushberry plant found only in the Atherton Tablelands in Queensland. This report probably sums it up fairly well. An alkaloid called EBC-40 has been isolated and injected into tumours in animals. “A single injection of the drug directly into melanoma models in the laboratory, as well as into cancers of the head, neck and colon in animals, destroyed the tumours long-term in more than 70% of cases, the study’s lead author, Dr Glen Boyle, said. In preclinical trials we injected it into our models and within five minutes, you see a purpling of the area that looks like a bruise, .... About 24 hours later, the tumour area goes black, a couple of days later you see a scab, and at around the 1.5 week mark, the scab falls off, leaving clean skin with no tumour there. The speed of action certainly surprised me. Researchers believe the drug triggers a cellular response which cuts off the blood supply to the tumour by opening it up.”

It has been used in about 300 clinical cases in dogs, horses and other animals by veterinary practitioners, and to the best of my knowledge and belief, it was dispensed only for cases in which biopsies had shown the tumours to be malignant. This was an improvement on the Devil’s Apples ‘cures’, which affected only non-malignant tumours. I personally see the fast effect of the blushberries as being clinically spectacular even though it was effective in only 70% of cases.

Obviously, there are thousands of potentially useful plant products out there waiting to be identified and trialled for medical purposes.
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Re: Proven benefits of natural foods, products, and remedies

Postby doogles on October 23rd, 2015, 6:46 am 

Salicylic acid by the way, was only ever used externally as far as I know. We used to make up an ointment in the 1950s as a debriding agent for proud flesh.

I assume that this thread is not going to cover the field of human nutrition and degeneration as extensively discussed by Weston Price in 1931.

There is another developing field in this area. An acquaintance of mine, Professor Lindsay Brown is doing some research in this area at the University of Southern Queensland. He sent me references to a few of his papers some years ago.

This one http://jn.nutrition.org/content/140/5/946.short produces evidence that olive leaf extract reduces all sorts of metabolic problems in high-carbohydrate-, high-fat-fed rats.

This one http://journals.cambridge.org/action/di ... 4510002308 shows that “anthocyanins, phenolic acids and carotenoids are the predominant phytochemicals present in purple carrots. High-carbohydrate, high-fat diet-fed rats developed hypertension, cardiac fibrosis, increased cardiac stiffness, endothelial dysfunction, impaired glucose tolerance, increased abdominal fat deposition, altered plasma lipid profile, liver fibrosis and increased plasma liver enzymes together with increased plasma markers of oxidative stress and inflammation as well as increased inflammatory cell infiltration. Purple carrot juice attenuated or reversed all changes while β-carotene did not reduce oxidative stress, cardiac stiffness or hepatic fat deposition.”

Another suggests that Chia seeds have a similar protective effect.

These fat rat models are obviously designed to simulate human metabolic syndrome.

This is another one FWIW, referring to the effects of omega 3 fatty acids by the same research group - Omega-3 fatty acids and metabolic syndrome: effects and emerging mechanisms of action H Poudyal, SK Panchal, V Diwan, L Brown - Progress in lipid research, 2011 – Elsevier
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Re: Health benefits of natural foods, products, and remedies

Postby SciameriKen on October 23rd, 2015, 10:12 am 

BioWizard » Thu Oct 22, 2015 9:54 pm wrote:To me, this suggests that either there are some other COX enzymes that we don't know about which also get inhibited by NSAIDs (although the study does provide some evidence that it's likely just COX-2) , or that purified COX fails to bind salicylic acid in vitro for whatever reason. NFkB does not seem to be directly relevant to the molecular mode/mechanism of action (MMOA). Either way, both aspirin and salicylic acid appear to indeed work by inhibiting cyclooxygenase activity (whoever is catalyzing it) on arachidonate.

That was a fun quick hunt. Thanks for that tangent Sciameriken.


I believe Shoelson was more interested in the NFkB mechanisms, not so much COX inhibition. He is working with a new drug which is effectively a dimer of salicylic acid (Salsalate) that seemingly is having benefits during type II diabetes (http://www.ncbi.nlm.nih.gov/pubmed/23817699).
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Re: Health benefits of natural foods, products, and remedies

Postby neuro on October 23rd, 2015, 11:31 am 

BioWizard » October 22nd, 2015, 10:27 pm wrote: acetyl salicylate rapidly hydrolyzes in the body into salicylic acid, therefore the mechanism of action of aspirin (which according to them is quickly converted to salicylic acid in the body) can't be through acetylation and inhibition of COX (since salicylic acid coming from an aspirin-grade dose can't do these things). So they're saying that aspirin (which according to them immediately becomes salicylic acid in the body) has to be inhibiting COX activity through some other mechanism.

Just a simple note I usually offer to my students:
COX produces PGI in endotelial cells (an inhibitor of platelet aggregation), whereas it produces thromboxane (TXA) in platelets (a powerful pro-aggregant). But, platelets are not cells, they are cell fragments, they do not possess protein (and enzyme) synthesis apparatus. Thus, if you IRREVERSIBLY block COX (by acetylating it) they won't be able to aggregate, and you must wait for new platelets to be formed. The enothelium will instead keep synthesizing new enzyme, so that PGI will prevail on TXA and you get an anti-thrombotic effect. Notice that you need LOW DOSES of aspirin, otherwise this game does not work: PGI would also be virtually abolished.

This does not occur with other NSAIDS that REVERSIBLY block COX, and the effect is even opposite if you only block COX2 enzyme subtype.
Selectively blocking COX2 (which is actively upregulated in inflammation and would be the ideal target of an anti-inflammatory drug) was a major objective in drug discovery, for a while, in the hope that we would be able to control inflammation (and pain, fever) without blocking COX1, that is constitutively produced and plays many other physiological roles, among which gastric protection (by production of PGE). But, alas, COX2 selective inhibitors (the "coxibs") have mostly gone out of market (except for nimesulide) because they turned out to increase the risk of cardiovascular accidents.
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Re: Proven benefits of natural foods, products, and remedies

Postby BioWizard on October 23rd, 2015, 12:17 pm 

neuro all true, althought the cardiac issues of coxibs appear to be largely class related rather than specifically due to selective COX-2 inhibition.
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Re: Health benefits of natural foods, products, and remedies

Postby Watson on October 23rd, 2015, 2:47 pm 

BioWizard » Thu Oct 22, 2015 4:59 pm wrote:
Watson » 22 Oct 2015 04:57 pm wrote:Something Edgar Casey suggested was almonds, but I don't recall what the benefits were.

Also Cheyenne pepper, raw vinegar and tomatoes juice.


Thanks Watson. If you have any studies that support the use of these foods, and for what particular indications, please post them. The idea is to keep this as evidence based as possible.


There is a lot of information on the subject of Almonds and/or Edgar Casey. The tomato juice concoction may be more difficult, but I think it is more of a cleanse for the system. Cheyenne pepper has its own benefits.

Several Cayce readings specifically recommend almonds in the context of cancer prevention, usually with other elements of diet.

The most often quoted readings say:

"Those who would eat two to three almonds each day need never fear cancer." (1158-31)

"If an almond is taken each day, and kept up, you'll never have accumulations of tumors or such conditions through the body." (3180-3)


http://www.healingcancernaturally.com/c ... dings.html
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Re: Proven benefits of natural foods, products, and remedies

Postby Watson on October 23rd, 2015, 3:03 pm 

I can find lots on the health benefits of the individual ingredients, but nothing on the mixture, but I'm pretty sure I heard of it through Casey.
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Re: Proven benefits of natural foods, products, and remedies

Postby Braininvat on October 23rd, 2015, 7:02 pm 

Are you offering a psychic, Cayce, as an expert in oncology?

I mean "2-3 almonds a day..." and we need never fear cancer?

I'd say, dig a little deeper into real nutritional research, and forget these carnival sideshows.
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Re: Proven benefits of natural foods, products, and remedies

Postby Watson on October 23rd, 2015, 7:56 pm 

True enough, but I was replying to Bio's request for more info about my post, which included Casey. Also, the link provided does suggest Casey was not totally wrong and may have got some of it right.
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Re: Proven benefits of natural foods, products, and remedies

Postby Watson on October 24th, 2015, 3:45 pm 

There is a multitude of sites agreeing with the many health benefits of almonds, independent of what Casey may have thought.

The downside I did find was that these health benefits have resulted in increasing demand for almonds. The almonds are grown in California, in the middle of a prolonged drought and almonds require a steady supply of a lot of water. Rivers get drain to the extent fish are at risk.

http://www.theatlantic.com/health/archi ... ts/379244/
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Re: Proven benefits of natural foods, products, and remedies

Postby vivian maxine on October 24th, 2015, 3:55 pm 

Two that I can guarantee work because I've used both often.

Cola syrup for stomach aches. It isn't new with me, though. Druggists used to bottle and sell the syrup for just that purpose. I just take a swallow of a cola drink. Not much, an ounce or two does it.

Rooibos Tea for nausea or stomach upset. Herbalists list it for this purpose and it does work, I promise.
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Re: Proven benefits of natural foods, products, and remedies

Postby Braininvat on October 24th, 2015, 4:35 pm 

Watson, thanks for The Atlantic link. I had heard elsewhere about the ecological stresses of almond farming and referenced it in that NYT article I posted a while back on how much water common CA crops need per serving. I notice the crop did poorly this year and those 6 oz. Blue Diamond cans really shot up in price. I was happy to not buy, because the almond, alas, is my least favorite nut. Pistachios and pecans are wonderful.
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Re: Proven benefits of natural foods, products, and remedies

Postby Watson on October 24th, 2015, 5:14 pm 

Yes I thought of it when I was reading this article. Over a gallon of water per almond. Not the best crop to grow in a desert.
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