A Thought on the Practice of Functional Medicine and Clinical Nutrition as We Enter a New Year and a New Decade: How Does the Massive Escalation of Prescription and Over-the-Counter Drug Use Make Difficult Patients “Difficult” (Hint – It May Not Be What You Think) – Part I


Based on both my observations with patients and feedback from you on your patients, it has become clear that, while our successes with clinical nutrition and functional medicine are many, there is still a growing group of chronically ill patients who experience significantly suboptimal quality of life improvements even after following our lifestyle and/or supplemental recommendations.  This has led to a frequent comment I have not only made myself but have heard from many of you – It seems like the most difficult to assist chronically ill patients are more difficult to assist today than they were in the past.  What is my first thought when encounter these patients and have these conversations?  Invariably, it is the following:

What did we miss?

Over the last 1-2 years, I have been focusing my thoughts, writings, and lectures on this very question by addressing key metabolic issues that are often ignored clinically.  These key metabolic issues, such as acid/alkaline imbalance due to suboptimal potassium intake, suboptimal intake of protein and/or amino acids, and loss of muscle mass, are based on published research.  Has addressing these issues with this new breed of chronically ill patients delivered satisfactory results?  My own experiences plus your feedback indicates that the answer is a definitive yes.  However, there is still a significant subgroup of this current batch of chronically ill patients who either do not respond as we would like to our efforts or, even more frustratingly so, experience seemingly paradoxical exacerbations of chief complaints after implementing well-constructed, well thought-out, lifestyle and supplemental protocols.  In response to these challenging patient scenarios, I ask again – What did we miss?

To begin to answer this question, I think about my experiences with very difficult chronically ill patients when I began my career in the supplement industry in 1985.  What did the vast majority share in common?  As you might expect, diets high in refined foods containing added sugars and salt were virtually ubiquitous.  Interestingly, I am finding this is decidedly not the case with a high percentage of today’s difficult chronically ill patients.  Due to the Internet and a much more health-conscious mass media, many, if not most, of these difficult chronically ill patients I encounter or hear about are either eating or making a genuine effort to eat a diet that is reasonably within currently accepted clinical nutrition and functional medicine guidelines.  Yet they are still experiencing persistent and sometimes debilitating chronic symptoms.  So again I ask:  What was missed?

What I have been noticing more and more about these patients over the last year or so is a trend that I have commented on with some of you but never addressed in this forum until now – the increased use of prescription and over-the-counter medications.  It seems to me that, unlike 30 years ago when it seemed that the biggest problem with most difficult chronically ill patients was the ingestion of a highly refined, poor quality diet, today’s difficult patients, even though their diets have improved from what we saw 30 years ago, are invariably ingesting one or more prescription and/or over-the-counter drugs.  Furthermore, use of these drugs is, most often, not a short-term phenomenon but a situation that has gone on for years, with sometimes a significant lack of monitoring by the prescribing physician for continued need or dose revision.

Can this ubiquitous use of sometimes several prescription and over-the-counter drugs by the most difficult chronically ill patients be a major contributor to the poor results we are getting more often with these patients?  Is this the answer to “What did we miss?”

In this newsletter to start the new year and the new decade I would like to present research to support my hypothesis that one of the biggest challenges we will have with the difficult patients of the 2020s and beyond is assisting them despite the very real possibility that their often lengthy list of medications is contributing to their chief complaints.

Of course, by now you may be thinking that I am wasting your time by belaboring what we already well know.  You may be thinking “I already know that drugs have major side effects and interactions with supplemental nutrients and herbs plus other drugs, all of which can make resolution of chief complaints more difficult in chronically ill patients.  Why discuss this again!!”

Fortunately, hopefully to your relief, I will not be going down this well-trodden path one more time.  Instead I would like to highlight other ways that medications interact, often to the detriment of patient health.  These interactions include those with dietary constituents that are often found in patients’ diets, even in diets that many would consider to be “healthy” or fairly innocuous in terms of patient chief complaints.  Still another rarely considered interaction that may have critical clinical implications will also be explored in this series – cannabis in its various, currently available forms.  Finally, another underappreciated drug interaction will be explored – the impact of drugs on magnesium metabolism.


It is now fairly well known that grapefruit and grapefruit juice ingestion is now contraindicated with many medications because grapefruit and grapefruit juice can have a significant impact on the metabolism of many medications, which can sometimes be very detrimental to patient quality of life.  Fortunately or unfortunately, depending on your point of view, grapefruit and/or grapefruit juice is not a common constituent in the diets of the vast majority of patients, whether or not they are eating “healthy.”

However, there are interactions between medications and food constituents consumed by the vast majority of Americans, even Americans who claim to eat “healthy,” that I feel are vastly under appreciated.  Could these underappreciated, often unknown food/medication interactions be at least part of the answer to the question – What did we miss?  I would like to answer this question by reviewing the fascinating, recently published paper “Drug interactions of cola-containing drinks” by Nomani et al (1).  Before I begin my review of this paper, though, I would like to answer a question that may be running through your mind after seeing the title of this study:

“Why do I need to read about this study?  After all, I am well-aware of the health-related dangers of colas and certainly recommend that my patients who consume these products refrain from drinking them.”

The reason that this study is important for us to read in relationship to the near universality of pharmaceutical use among our patients is the fact that it addresses in detail one of the constituents of colas that is found in many more consumables than colas.  What is this consumable?  As you can probably guess, it is caffeine.

Some thoughts and research on caffeine

Before presenting some highlights of published research on caffeine, I would like to share some thoughts.  First, as you will see, caffeine consumption, because it can be found not only in colas and coffee, but in analgesic pharmaceuticals (Excedrin) and increasingly popular energy drinks, occurs in varying degrees among the vast majority of the US population.  However, after perusing some research on the subject, I found an incredible amount of controversy in terms of the health impact of caffeine.  For, depending on dose and form, research has shown that it may be detrimental, innocuous, or even beneficial to health.  Specifically, virtually every study I read on caffeine in the context of coffee suggested that, at doses often consumed (300-400 mg caffeine per day which equals approximately 3-4 cups of coffee), caffeinated coffee is not a contributor to increased mortality or occurrence of major diseases such as cardiovascular disease, type II diabetes mellitus, and cancer.  Furthermore, caffeinated coffee may actually promote longevity and avoidance of disease due to the presence of numerous beneficial polyphenolic compounds that naturally occur in coffee (2).  Similarly, from what I could see, the caffeine contained in medications such as Excedrin is considered to quite innocuous.  In contrast, as noted in the paper “Caffeinated energy drinks – A growing problem” by Reissig et al (3) caffeine in energy drinks can pose a significant health risk:

“There are increasing reports of caffeine intoxication from energy drinks, and it seems likely that problems with caffeine dependence and withdrawal will also increase.”

Furthermore, in line with the subject matter of this monograph about the adverse interactions of certain drugs with ubiquitous, often thought to be completely innocuous food substances, the authors state the following about the interaction of caffeine and alcohol:

“The combined use of caffeine and alcohol is increasing sharply, and studies suggest that such combined use may increase the rate of alcohol-related injury.”

Interestingly, despite all the research on the deleterious, innocuous, and health-promoting aspects of the various caffeine-containing substances found in our society, I could find no research that addresses, for me, some very important clinical questions:

What is the impact of caffeine, given that the effects of caffeine are heavily dose-dependent, when the cumulative amount comes not from any single source but from several highly popular sources?   For example, what is the impact when a generally safe dose of 3-4 cups of coffee per day are combined with an energy drink and a caffeine containing drug such as Excedrin?  Furthermore, what is the impact on health when caffeine from all these different sources is combined with the massively increased utilization of prescription drugs and non-caffeinated over-the-counter drugs?  Finally, what is the impact when we supplement patients who consume this variety of caffeinated substances and pharmaceuticals with various herbals, and macro- and micronutrients?

Could the impact of the above be what we missed with those increasing numbers of very difficult patients who are not responding to the usual lifestyle and supplemental protocols that have been effective over the years with so many other patients?  In this monograph I will review some papers that I feel provide some support and understanding to the idea that, given the complex interactions between bioactive substances such as caffeine found in so many consumables and many commonly used medications, the use of medications must be given top priority anytime we encounter a difficult, chronically ill patient who is not responding to the usual.  For, as I hopefully have convinced you by now, the official list of drug side effects found in the PDR does not even begin to describe all the ways today’s generation of prescription and over-the-counter drugs can contribute to ill-health and poor quality of life when we consider the actual, “in the trenches” ways these substances interact with the things we ingest.

An in-depth examination of caffeine

Before discussing the cola/drug interactions featured in the Nomani et al (1) paper, I would like to explore in depth the toxicology of the substance so prominently featured in the Nomani et al (1) paper, caffeine.  To do this I will highlight some quotes from “The clinical toxicology of caffeine: A review and case study” by Willson (4).  The first quote I would like  to feature provides specific data on the main reason I feel it is so important for us to consider the impact of caffeine on drug usage in our patients.  Its usage in this country and, indeed, the world is incredibly common:

“Nowadays, caffeine is the most widely consumed psychostimulant in the world.  It is estimated that caffeine is being consumed by more than 80% of the world’s and up to 89% of the United States population.  The average daily consumption of caffeine varies depending on the survey, years conducted and sources considered but has most recently (i.e., 2011-2012) been reported as 142 mg per day for adults and children in the United States, a decrease from previous years (e.g., average consumption of 175 mg/day in 1999-2000) largely attributed to a reduction in soda consumption.  Coffee purchased from the grocery store and tea remain the largest contributors to caffeine intake in the United States overall, although the contribution from energy drinks, while still a relatively minor contributor overall has increased.”

As was mentioned above, the impact on health of caffeine is largely determined by dose.  Willson (4) states”

“While caffeine is generally thought to be safe in moderate amounts (i.e., ≤400 mg per day) in healthy adults, it is clearly not an innocuous compound and can cause significant toxicity and even lethality (i.e., most commonly via myocardial infarction or arrhythmia) if sufficient quantities are consumed.”

Before continuing, please note again the phrase “healthy adults” in the above quote.  Given that the theme of this newsletter is issues facing the unhealthy adults we encounter more and more often, it is important to also note that these unhealthy adults may have adverse reactions to amounts of caffeine lower than the generally safe amounts indicated above:

“Some sensitive individuals may also experience toxicity and lethality at doses not normally associated with such outcomes.”

The next quote provides detail on what might be expected clinically at any given dose of caffeine:

“Caffeine is known to have generally dose-dependent effects with positive or desirable effects at lower doses (i.e., ≤400 mg) and undesirable effects generally above this level of intake, although there is substantial inter-individual variation.  For example, increased arousal, alertness, concentration and well-being (e.g., increased elation, peacefulness and pleasantness) have been noted at doses of 250 mg in human subjects, whereas a dose of 500 mg was shown to increase tension, nervousness, anxiety, excitement, irritability, nausea, paresthesia, tremor, perspiration, palpitations, restlessness and possibly dizziness.  High, sub-lethal doses (~7-10 mg/kg) in normal adults may also cause symptoms such as chills, flushing, nausea, headache, palpitations and tremor, although individual responses vary significantly.”

Absorption of caffeine – As noted in the following quote, caffeine is absorbed quite readily:

“Caffeine has rapid and complete (i.e., 99%) absorption from the small intestine after oral administration in humans due to its weakly basic nature…”


“When consumed with food and perhaps some beverages, absorption may be slower compared to ingestion of caffeine alone on an empty stomach presumably due to a delay in gastric emptying.”

Systemic distribution of caffeine

“Caffeine is distributed throughout the body after being absorbed from the gastrointestinal tract (the small intestine in particular), entering all tissues via cell membranes (i.e., due to its lipophilic moiety or moieties and limited plasma protein binding) and entering intracellular tissue water.  It readily penetrates the blood-brain barrier as well.”

In addition:

“Caffeine is also not known to accumulate in tissues.”

Metabolism of caffeine – Because, as noted in the Nomani et al (1) paper, the way caffeine is metabolized may be the main factor in determining many of its adverse effects on drug metabolism, I would like to examine Willson’s (4) comments on caffeine metabolism in depth.  As you will see, caffeine is primarily metabolized via phase I detoxification enzymes:

“Caffeine is primarily metabolized to 1,7-dimethylzanthine (paraxanthine) in the liver via the CYP isozyme CYP1A2, which causes 3-demethylation of caffeine.  Paraxanthine is the major metabolite (approximately 80%) of caffeine biotransformation.  Interestingly, paraxanthine itself is also pharmacologically active albeit with potentially lower toxicity than caffeine.”

Other phase I enzymes along with CYP1A2 convert caffeine to still more metabolites:

“CYP1A2 is also responsible for, along with to some extent CYP2E1, the 1 and 7-demethylation of caffeine to 3.7-dimethylxanthine (theobromine) and 1.3-dimethylxanthine (theophylline), respectively, which are also pharmacologically active.  Theobromine accounts for approximately 11%, while theophylline is around 5% of caffeine metabolites.”

Interestingly, the number of metabolites of caffeine does not end there:

“Overall, more than 25 metabolites have been identified in humans after caffeine administration, demonstrating rather complex metabolism.”

Is some caffeine excreted unchanged?  Yes – but only a small amount:

“Less than 5% of ingested caffeine is excreted unchanged.”

Of course, as we have become well aware of during the last few years, SNPs of detoxification enzymes can occur, which can add still another important variable to consider in relationship to caffeine metabolism and the impact of caffeine on drug metabolism:

“There is significant inter-individual variation in CYP1A2 activity in humans, the majority of which is inherently due to genetics…”

However, as we also well know, epigenetic/environmental factors can also affect enzyme activity:

“…to some extent environmental factors (e.g., smoking, Brassica vegetables, charcoal grilled meat and some medications such as omeprazole are known to induce CYP1A2 activity while oral contraceptives, cimetidine, fluvoxamine and Apiaceae vegetables are known to inhibit CYP1A2 activity) which may mask genetic influences.”

Furthermore, if that were not enough, coffee itself can affect CYP1A2 activity:

“Coffee itself has been shown to increase CYP1A2 activity, although not consistently.”

How much can CYP1A2 activity vary from person to person?  Willson (4) states:

“Demonstrating inter-individual variation, analyses at the population level have found coefficient of variation values around 40% for CYP1A2 activity in humans.”

As I hope you can see, because of caffeine’s somewhat complex relationship with detoxification pathways, its relationship with the detoxification of pharmaceuticals is also somewhat complex.  Could this complexity be what was missed in today’s difficult patient who, more often than not, is consuming one or more medications?  I will provide more evidence to support this contention when I discuss the Nomani et al (1) paper.

Elimination of caffeine

“The vast majority of caffeine is eliminated from plasma via CYP1A2-mediated clearance in which paraxanthine is the main metabolite.  Elimination occurs mainly via renal excretion in urine (~85-88%), although fecal excretion also takes place to a limited extent (i.e., around 2-5%).”

How fast is caffeine eliminated?  This can also vary greatly from person to person:

“The clearance and elimination half-life of caffeine also show significant inter-individual variation.”

How much can it vary?

“…the elimination half-life is variable with an average of approximately 3-6 hours in healthy humans.  However, these values can vary substantially from 2.3 to 9.9 hours.”


“…the clearance of caffeine can be substantially reduced as the dose of caffeine rises.”

Why is this?  As noted in the following quote, the main reason is that the amount of CYP1A2 is limited:

“This is thought to occur due to saturation of the CYP1A2 isozyme, likely by the main metabolite of caffeine, paraxanthine which is also a substrate for the isozyme.”

Thus, as more caffeine is consumed, more of its metabolite, paraxanthine, is formed, which slows the ability of CYP1A2 to metabolize more caffeine.

The impact of caffeine on potassium metabolism

The last piece of information I would like to feature from the Willson (4) paper revolves around the mechanisms of the side effects of caffeine, one of which I feel is most important from a clinical nutrition perspective.  As I discussed at length in the “Potassium and sudden cardiac death” newsletter series, excessive caffeine intake can significantly lower serum potassium, creating a state of hypokalemia.  According to Willson (4), this is likely due to the impact of caffeine on the cellular Na+/K+ pump.  Furthermore, this effect on serum potassium can occur with even low or moderate doses of caffeine.

Interactions between drugs and cola

With the above introduction to caffeine in mind, I would now like to review the paper I mentioned before, “Drug interactions of cola-containing drinks” by Nomani et al (1).  The first quote I would like to feature makes it clear why it is so important to discuss cola when considering caffeine use:

“…a large observational study of Spanish households showed that in 2014, the second most common nonalcoholic beverage was cola.  Another study of Polish students of high-school and university age showed that cola-containing drinks (CCDs) were the most common caffeinated beverage consumed by this demographic.  Another epidemiologic study on bus drivers in a particular Brazilian city showed that 64.2% of them excessively consumed cola drinks.  In Iran, a large study of Tehranian adolescents’ snacks showed that they commonly consumed a cola-drink.”

Next, the authors state the basic premise of the paper:

“This wide use of cola-containing drinks is important in light of the fact that it is known that such drinks can interact with different drugs, especially when used concomitantly.”

The specifics of drug interactions of cola can be divided into two aspects.  The first, as suggested above, relates to caffeine:

“First, cola drinks are a well-known source of caffeine.”

How much caffeine is in cola?  The amount varies:

“The caffeine content in colas may range from 15 mg to 24 mg in an approximate 180 ml serving size.  However, in previous studies, as high as 55-56 mg of caffeine per 356 ml cola have been reported.  Also, 30 and 70 mg of caffeine per 200 ml of cola was reported by a study conducted in 2003.”

The second aspect of cola/drug interaction relates to an issue I have discussed many times in this forum over the years, acid/alkaline balance:

“The second property of cola drinks that give rise to CCD/drug interactions results from the acidic pH of most cola drinks, which primarily results from the phosphoric acid content.  This low pH and phosphoric acid content can be a source of several drug interactions…”

Cola/drug interactions – changes in pharmacodynamic properties

The next several sections of the Nomani et al (1) discuss the specific ways the two main aspects of colas – caffeine and acid pH – interact with drugs.  The first relates to what is known as “pharmacodynamic interactions.”  What are pharmacodynamic interactions?  The authors state:

“Pharmacodynamic interactions are interactions between drugs, which affect similar physiological pathways and directly influence each other’s effects.”

As you will see, caffeine predominates with this specific interaction.  To fully understand the nature of the interaction, though, it is important to understand one of the main mechanisms underlying the effects of caffeine:

“Caffeine exerts its effects through mechanisms like antagonizing adenosine receptors (AI and A2A).  Through this mechanism, caffeine can increase the release of various neurotransmitters in different regions of the brain.  Therefore, it has psychomotor stimulant effects and improves behavioral functions like vigilance, attention, mood and arousal.”

With the above in mind, how does caffeine interact with drugs:

“…it can potentially interfere with different psychiatric drugs like stimulants or sedative drugs.  There are reports of potential minor interactions between caffeine supplied from cola drinks with diazepam and barbiturates, possibly because of the minor stimulant effects of caffeine.”

Cola/drug interactions – pharmacokinetic interactions at the level of drug absorption

What are pharmacokinetic interactions?  Nomani et al (1) state:

“Pharmacokinetic interactions include interactions at the level of absorption, distribution, metabolism, and elimination of drugs, which all can affect the effective concentration of a drug at its site(s) of action.”

Absorption – The pharmacokinetic impact of colas on drug absorption specifically involves the acid pH of colas.  To introduce this absorptive interaction, the authors point out the following:

“At the drug absorption level, there are two important steps; the dissolution of the drug in gastrointestinal fluids and the diffusion of a drug from gastrointestinal membranes into the blood.  Many drugs are weak acids or weak bases and can exist in either the ionized or unionized form depending upon the pH of their environment.”

Because colas are acidic (Classic Coke, according to the authors, has the lowest pH of many colas with a pH of 2.5), they interact with drugs in the following way from an absorptive standpoint:

“…it has been shown that CCDs, when co-administered with drugs that are either weak acids or weak bases can lead to alterations in the rate and/or extent of their absorption due to changes in the rate and/or extent of dissolution or diffusion across a biological membrane.  In fact, it has been shown that co-administration of CCDs with weak bases can increase the gastric concentration of the drug and subsequently increase its overall absorption.  It has been suggested that this phenomenon may be due to the CCD affecting the dissolution or aqueous solubility of weakly basic drug substances due to a lower pH induced by the CCD.”

The next quote gives a specific example of how colas can affect drug absorption:

“…in an experimental study, ibuprofen, which is a weak acid, was co-administered with a CCD and the extent of its absorption was shown to increase.  The increased absorption of ibuprofen in an acidic environment may be due to an increase in the fraction of the unionized from of ibuprofen and a subsequent increase in its membrane diffusion and overall absorption following oral administration.”

Before continuing, I would like to hypothesize the possibility that the impact of the acidic nature of colas could be extrapolated to the other highly acid, processed foods typically ingested by many of our patients.  Therefore, could the effect on ibuprofen seen with colas also be seen with foods such as processed meats and refined grain products?  Furthermore, could this interaction with ibuprofen be seen with certain “healthy” acid-ash foods such as quality dairy and red meat products?  I feel this is a logical possibility.

In concluding this discussion on the impact of colas on drug absorption, Nomani et al (1) discuss other constituents of colas not mentioned above:

“Lastly, cola drinks contain phosphoric acid and sugar.  There are reports demonstrating prolonged gastric emptying due to these two components of CCDs.  Obviously, a prolonged gastric emptying time can affect the rate and extent of drug absorption.”

As I hypothesized above, could we extrapolate the impact of the sugar found in colas on drug absorption to sugar from other sources?  In my opinion, the answer is yes.

Finally, if that were not enough, the authors point out colas can affect the dissolution rate of the capsule in which many drugs are contained, which can also affect absorption.

Cola/drug interactions – pharmacokinetic interactions at the level of drug metabolism

As I highly emphasized above, probably the most clinically important way caffeine-containing foods and substances affect the impact of drugs is through alteration of drug metabolism.  Nomani et al (1) elaborate on the aspect of colas – caffeine – that affects the metabolism of drugs:

“…CCDs can be considered as a source of caffeine.  The biotransformation of caffeine is mainly restricted to the liver and involves the isoenzyme CYP1A2.  This isoenzyme is the most important metabolic pathway of some drugs, for example, clozapine.  Therefore, the caffeine contained in cola-drinks can potentially compete for binding to CYP1A2 and may competitively inhibit CYP1A2-dependent metabolism of other CYP1A2 substrates.  This interaction is more important for medications with a narrow therapeutic index.  This competitive inhibition by caffeine of medications that are metabolized by CYP1A2 may result in increased serum levels of this medication, which could give rise to toxic effects.  Thus, all drugs which are substrates of CYP1A2 could potentially be affected when they are ingested with excessive volumes of cola-containing drinks containing caffeine.  Clozapine, olanzapine, theophylline, and zolmitriptan are all examples of drugs that are substrates for CYP1A2.” 

Cola/drug interactions – pharmacokinetic interactions at the level of drug excretion

As you will see, the impact of colas on drug excretion involves the acidic pH aspect of colas.  Nomani et al (1) begin their discussion of this category of interaction by pointing out what most of us know, colas can lower the pH of the urine:

“It has been shown that CCDs can lower the pH of urine.  This is attributed to the phosphoric acid content of most CCDs.  Phosphoric acid is an inorganic acid and is excreted intact in the urine and, consequently, lowers the pH of urine.”

How do CCDs interact with drugs in terms of excretion?  Recall from above that drugs can generally be categorized as weak acids or weak bases.  With this in mind, the authors state:

“For weak bases in acidified urine resulting from the consumption of CCDs, the proportion of drug in the ionized form increases and, therefore, its reabsorption is reduced and, in turn, its overall renal excretion increases.  Conversely for drugs which are weak acids, the overall renal excretion decreases in acidic urine.  The pH-dependent nature of renal excretion for drugs that are either weak acids or weak bases also includes some metabolites as well.”

Why is this important from a clinical standpoint?

“Additional studies that evaluate the interaction between various weakly acidic and weakly basic drugs and CCDs is extremely important, especially if these drugs possess a narrow therapeutic index or are primarily eliminated from the body by renal excretion.  Phenobarbitol is an example of a drug which its renal elimination is reduced when the urine is acidified.  Another important example of a drug that has reduced renal elimination in acidified urine is methotrexate, which is a weak acid.  In fact, there are two case-reports of toxic effects of methotrexate when simultaneously administered with excessive amounts of CCDs.”

Nomani et al (1) go on to discuss the impact on renal health when the elimination of weak acid drugs is decreased by acidic substances such as colas:

“In addition, the effect of CCDs on the pH of urine can be important, especially for drugs that have the potential to precipitate in the kidneys and exert a nephrotoxic effect.  Again, methotrexate (a weak acid), when in acidic urine, precipitates in the kidneys in the form or crystals and may lead to nephrotoxicity.”

Can the caffeine in colas affect excretion of drugs?  While not as important as the pH of the urine, there are certain instances where caffeine can affect renal elimination of certain drugs.  Why?  It has to do with the fact that caffeine alters the renal reabsorption of sodium:

“Caffeine, by antagonization of A1 receptors in the kidney, can inhibit tubular reabsorption of sodium and then induce natriuresis and, subsequently, diuresis.”

This can affect the elimination of the drug form of lithium, as will be discussed in part II of this series when I finish my review of the Nomani et al (1) paper.

In addition, in part II of this series I will, as mentioned above, review other clinically important interactions of which we may not be aware that can have a major impact on those difficult, chronically ill patients whose lack of positive responses to our usual lifestyle and supplemental efforts leave us scratching our heads.  These include studies on the metabolic impact of caffeine when combined with sugar, the impact of drugs on magnesium metabolism, and the interaction of cannabis on drug metabolism.

Moss Nutrition Report #289 01/01/2020 – PDF Version


  1. Nomani H, Moghadam AT, Emami SA, Mohammadpour AH, Johnston TP, Sahebkar A. Drug interactions of cola-containing drinks. Clin Nutr. 2019;38(6):2545-51.
  2. Kim Y et al. Coffee consumption and all-cause and cause-specific mortality: a meta-analysis by potential modifiers. Eur J Epidemiol. 2019;34:731-52.
  3. Reissig C et al. Caffeinated energy drinks — A growing problem. Drug Alcohol Depend. 2009;99:1-10.
  4. Willson C. The clinical toxicology of caffeine: A review and case study. Toxicology Reports. 2018;5:1140-52.

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