Drug Therapy Versus Nutrient Therapy- There is a Difference!
Under this header there was an interesting discussion on Linked-in we want to communicate also via this site, especially by Dr Phil Sledz from Fundamental Health Solutions and one of our participants.
Here the discussion:
It’s important when we approach any condition, we should understand what is happening on a cellular level. By focusing on the cellular level of any health challenge, which involves our metabolic enzymes, we can have a greater effect on managing favorable outcomes for tough cases.
Is there a basic difference between drugs and nutrients?
Position 1: There is no basic difference between a drug working pharmacological and a nutrient working physiological, it is just a matter of what receptor the compound goes for. A nutrient such as palmitoylethanolamide decreases pain via the PPAR and TRPV1 receptors; opioids via the opioid receptors.
Position 2: There’s little doubt that receptors play a role in “receiving” a compound (drug or nutrient) however, I invite you to dig deeper and look at the underlying causal mechanism that allows a drug or a nutrient to work in the first place, that area being within our metabolic enzymes.
The notion that drugs (pharmaceuticals) are enzymatic inhibitors, and that nutrients are enzymatic activators is well documented today. Let’s start with drugs by going back to our pharmacology training while referencing the Physicians Desk Reference (PDR). The PDR contains all pharmaceuticals in use today, and explains their mechanism of action, the side effects, and even names the specific enzyme(s) they inhibit in our metabolism. This is how health professionals know that statin drugs inhibit the enzyme HMG-CoA Reductase to lower cholesterol which is made by our liver; NSAIDS inhibit the COX (cyclooxygenase) enzyme used to make certain pain mediating prostaglandins, and so on. Every drug listed in the PDR cites the chemical process that the drug “inhibits”. This entire book shares what is going on in our physiology by naming the enzymes and processes that are inhibited with a drug.
Certain drugs even go so far as to include the name “inhibitor” in their descriptors. This is because they are “enzymatic inhibitors”. SSRI’s, Selective Serotonergic Reuptake Inhibitors (Zoloft, Paxil, Prozac) block the enzyme that degrades Serotonin, so a depressed patient can hopefully experience elevated levels of Serotonin. DPRI’s (Wellbutryin, Zyban) are the same but for dopamine, again inhibiting an enzyme.
In chemistry, and our bodies, inhibition (or activation) can only occur by an enzyme. A reaction is either catalyzed or it isn’t. Once catalyzed, this sets forth a chain of enzymatic reactions called “cascades”. Cascades create multiple side effects with a drug (resulting in many pathways being “shut down”), and multiple benefits with one nutrient. For example, we know vitamin C does more than give our immune system a boost, it also helps build collagen, detoxifies areas of our liver, all through various enzymatic reactions. Of course acting on receptors plays a role; using the “lock and key” analogy, they key (drug or nutrient) must fit into the lock (enzyme) via a receptor. Yes, a receptor site is occupied however, receptors don’t catalyze reactions, only enzymes can do that.
Additionally, those of us in nutrition have repeatedly heard nutrients (mineral, vitamins, amino acid) referenced as “co-enzymes”, because they are enzymatic “co-factors”. A co-factor simply means it’s required for an enzyme to activate, without it the reaction will not occur. Minerals and Vitamins are used interchangeably with the term “co-enzymes”.
If there wasn’t a basic difference between drugs and nutrients, then the side effects, and consequences, would also be similar. I think you would agree that taking daily aspirin or Plavix to thin the blood has an entirely different outcome than taking daily fish oils with proteolytic enzyme supplementation to do the same. At the least the statistics show a difference with over a hundred thousand yearly hospitalizations for gastro-intestinal bleeding due to NSAID use. An entirely avoidable and unfortunate consequence.
This is an interesting point, but it has to be put in perspective. Various natural compounds have direct receptor actions, such as palmitoylethanolamide, and various drugs are no inhibitors, but go to receptors too: like L-Dopa, nicotine, posiive inotropic substances, salbutamol for instance, as a ß2 agonis.
So your thesis: drugs (pharmaceuticals) are enzymatic inhibitors, and that nutrients are enzymatic activators is well documented today…is not (totally) correct. drugs can be enzymic activators too.
For getting the difference clear, we need to dig deeper and do not loose ourselves in too easy formats of thinking.
I feel that we should be more receptive to what Erminio Costa said once on the topic of developing new compounds: to follow were nature leads.
I do not have a clear idea on the basic difference between a drug and a natural compound, only natural compounds act on receptors and have been developed by evolution over millions of years, and drugs have been developed from synthesis to patients in less than 10 years….
I enjoyed reading your post(s). Receptor selection plays a large role as to what gets activated (or not) beyond the receptor site. For anything to “fit” into a receptor, this explanation refers back to the lock and key mechanism I described in the article. Just to clarify, I didn’t say that all drugs are inhibitors, but yes, a large part of American pharmacology seeks to focus on metabolic enzyme inhibition to manipulate our chemistry, and having it fit selectively into a receptor is part of this process. Anything that “blocks, inhibits or antagonizes” is doing so to an enzyme, via a receptor. If you have an opportunity to sift through the enormity of the PDR, or better yet randomly open up this text and select a drug, it will be a challenge to find something that is not an enzymatic inhibitor, or doesn’t include enzymatic inhibition where agonists and neurotransmitters are being used as part of the formulation. There’s so many examples of enzyme inhibitors in the PDR, its too large of a task to include them all in this short commentary. HIV Protease inhibitors, TNF-alpha inhibitors (for arthritis and Crohns), Histamine and Parietal cell blockers to suppress stomach acid production (reflux), ACE inhibitors for hypertension, Beta blockers (tremor, migraine, Arial-fib), Calcium channel blockers (hypertension), acetaminophen found in Tylenol, every anti-fungal med ending in “ole”, and so on.
Nutrients (grown properly, not synthetically) have the ability to self regulate with all their cofactors and synergists comprise their chemistry. Nutrients made with toxic tag alongs (binders, fillers, glues for encapsulation, additives, poor quality gel-caps, etc.) create toxic effects such as upset stomach, headache, muscle twitches, fatigue, etc.
Synthetic hormones are another example, which do not directly catalyze an enzyme, but create the proper surrounding “chemistry” needed to catalyze chemical reaction, much like pH and temperature.
When a receptor is “activated” this means that the surrounding metabolic enzymes that work within a receptor, and connect to a receptor, are being catalyzed and set into action. Whenever new “proteins” are being discovered that fold, manipulate or change the outcome of a body reaction in any way…that’s an enzyme, it just hasn’t been named as such (yet). Identifying enzymes is very hard, often times an enzyme has to be “caught” and “suspended”, which is very challenging, especially since some enzymes appear and degrade in milliseconds (and less), such as with neurotransmitters.
Nicotine, is a stimulant (activator) that has been accompanied with modifying agents (Inhibitors) found in cigarettes, such as menthol. Menthol and other chemicals help prevent its breakdown so it can last longer on the receptor. Nicotine appears in foods naturally, such as naturally grown tobacco, tomatoes, potatoes, eggplants, certain herbal teas and cauliflower. Cigarettes use inhibitors to help the nicotine “last longer” on the receptor site. Cigarettes also contain MAO inhibitors to artificially induce higher amounts of dopamine (an effect of nicotine), similar to MAO inhibiting drugs for depression. These are example of tag along inhibitors used to amplify a drug like reaction, so we see more examples of metabolic enzyme inhibition occurring. We notice that we don’t get the same nicotinic effects from cauliflower as we do from cigarettes.
Palmitoylethanolamide (PEA) is an endogenous fatty acid, with an amide (protein) attached, and yes they belong to a class of agonists as you pointed out, and it is also found as a nutrient in its un-tampered form. PEA can be found in high amounts in blue-green algaes, cheddar cheese. Consuming these foods does not yield the same result as PEA in a modified pharmaceutical form, so we can see that “side effects” (from the drug) come from molecular modifications to its chemical structure. They act very differently, for many of the same reasons I mentioned in the previous paragraph. This brings up an interesting point…
When pharmacology is seeking to create a drug, it does so through “molecular mimicry”. Which means that all drugs attempt to mimic a natural agent already seen in nature, so our body can “recognize it” and bring it into the intended location, however due the laws of drug production in our country, it must be modified in some way to reclassify it as a drug. It may be something grown in nature (PEA, salicylic acid, etc), or an agent made endogenously in our bodies. A great example of this is Salicylic acid, which comes from willow bark. Acetylsalicylic acid is the modified (drug) version used in Aspirin, which has a very different effect metabolically speaking than the nutrient form which is found in willow bark, raisins, blackberries, etc. Both salicylic acid (nutrient) and acetylsalicylic acid (drug) affect the COX enzyme and decreases its activity, but do so in different ways, through different enzymatic cascades.
L-Dopa is converted by two enzymes in the cascade in order to make dopamine. Therefore, it is not L-Dopa that lands in the receptor site, but dopamine, after converted by they body’s enzymes. Once it’s in a dopamine form, then it can be used as such. It’s common practice to administer L-Dopa along with COMT (another enzyme) inhibitors. COMT inhibitors are used in all Parkinsons disease treatment. So we see yet more examples of enzymatic inhibition with neurotransmitter drug use. L-Dopa is also commonly used with other enzyme inhibitors to boost the treatment called DDCI’s (another long one so I’ll just abbreviate).
Both L-Dopa and Tyrosine, the amino acid found in most meats, “can” metabolize into dopamine (provided other key nutrients are present). However, the effects of L-Dopa and Tyrosine are quite different, especially considering side effects.
Honestly, I agree with you whole heartedly on virtually all that you’re saying. The main impetus of my message is that there is a mechanism, or activity, that occurs beyond the receptor site caused by a metabolic enzyme. Once activated, or inhibited, there are follow on cascades which again involve additional metabolic enzymes. Pharmacology in America really seeks to go after inhibition as a focus. In other countries, nutrients are classified as drugs, Germany is one example of that…I hope it never comes to this in the states.
This tendency making supplements and foods into drugs brings up a hurdle so high that these foodcompounds will never than be able to reach the patient anymore. This is a real thread. The introduction of Souvenaid for Alzheimer in the Netherlands provoked straightliners to attack government and ask to put Souvenaid in the class of drugs in stead of food for medical purposes. What can we do?