Patrick Cox calls coffee a "health food," and the single most important food item available at the grocery store. Throw in a steak (protein) and who needs anything else? Okay, fiber. We need that. Coffee, steak, vegetable… maybe a beer.
Coffee, Tea Or P53
Courtesy of Patrick Cox of Transformational Technology Alert
Serious historians have proposed that the introduction of coffee into the Western diet contributed significantly to both the Enlightenment and its offshoot, the American Revolution. The idea is not such a stretch.
Given the lack of modern water purification and plumbing technologies, beer was routinely consumed in Great Britain in the 1700s to prevent water-borne diseases. Though alcohol at the concentrations common in beer may not always kill pathogens, it does keep them from growing in beer that has been boiled during the brewing process.
When coffee came onto the British scene in the 1500s, it provided a popular and alternative way to take water safely. As with tea, pathogens were killed during the brewing process. Coffee, however, is often viewed as the disreputable cousin of tea, which is widely regarded as healthful. Coffee usually has higher caffeine levels and that difference may have quite profound implications.
In those days, coffee was much more expensive and few people had experience brewing the stuff. Coffeehouses sprang up in response, but they didn’t normally sell individual cups. Rather, they charged an entry fee, after which java flowed freely. The result was that hyperactive groups of coffee drinkers began to pop up in place of semi-sedated beer drinkers.
Students and merchants found these establishments pleasant places to study, do business, and talk. Lacking Wi-Fi connections, merchants who tracked current events and their impact on business would announce major news to the entire assemblage. Naturally, a lot of discussions turned to politics and philosophy. Arguments took place and movements were born.
Just as contemporary politicians would like to regulate political speech, especially on the Internet, British royalty took a dim view of the free and often antiauthoritarian ideas associated with coffee and coffeehouses. In 1675, “A proclamation for the suppression of coffee-houses” was issued by King Charles II.
The justifications were helpfully included in the proclamation.
Whereas it is most apparent, that the Multitude of Coffee-Houses of late years set up and kept within this Kingdom, the Dominion of Wales, and the Town of Berwick upon Tweed, and the great resort of idle and disaffected persons to them, have produced very evil and dangerous effects; as well for that many Tradesmen and others, do therein mis-spend much of their time, which might and probably would otherwise be imployed in and about their Lawful Callings and Affairs; but also, for that in such Houses, and by occasion of the meetings of such persons therein, diverse False, Malitious and Scandalous Reports are devised and spread abroad, to the Defamation of His Majesties Government, and to the Disturbance of the Peace and Quiet of the Realm …
Many efforts all over the world have been made to stamp out the demon bean. Though such efforts have failed, coffee is part of our lives and our culture.
Edward Lloyd opened his coffeehouse “The Angel” in 1650. The Oxford hangout of merchants and shippers eventually morphed into Lloyd’s of London, the best-known insurance company in the world. In Scotland, the tenets of the Enlightenment were worked out in coffeehouses where works by Adam Smith and Spinoza were passed around.
Daniel Webster called the Boston coffeehouse, Green Dragon Tavern, “headquarters of the Revolution.” Open from 1697 to 1832, it played a role in the birth of America and was frequented by the likes of John Adams, James Otis, and Paul Revere who met there to conspire. The New York Stock Exchange and the Bank of New York were first coffeehouses.
Still, coffee is regularly maligned, usually from some sort of health perspective. I frequently hear people say they’ve cut out coffee for health reasons.
My reaction is bafflement. When asked about such an insane self-flagellation, most of these decaffeinated martyrs express some vague sort of belief that coffee just must be bad for us. After all, it makes you alert and happy. Happier, at least.
Coffee is health food. It is the primary source of antioxidants in the American diet and I consider it the single-most important food item available in most grocery stores. I wasted a lot of time, while writing this piece, trying to come up with some theory that explains the practice of forming extreme opinions about diet and health with no consideration of actual evidence. While this has always been the case, we live in an age that gives us instant access to the peer-reviewed literature via Google Scholar. There’s no excuse.
The man who influenced my views about coffee most was Mark A. Smith, PhD, professor of Pathology at Case Western Reserve University. Smith was tragically killed by a drunk driver a few years ago, but his impact remains. He served on the editorial board of over 200 journals including Science Translational Medicine, the Journal of Neurochemistry,and the American Journal of Pathology. He was director of Basic Science Research at the University Memory and Aging Center and editor-in-chief of the Journal of Alzheimer’s Disease.
We weren’t close friends, but he was always available to generously answer my questions and talk about the things he thought were important. One of those things was the efficacy of coffee as a disease preventative and life-extension agent.
Scientists of his standing are famously reticent to speak the plain truth, but Smith was surprisingly frank in his endorsement of coffee. More importantly, as editor-in-chief of the Journal of Alzheimer’s Disease, he published a special journal issue titled “Therapeutic Opportunities for Caffeine in Alzheimer’s Disease and Other Neurodegenerative Disorders.”
While the JAD is an important and expensive journal, he made the issue free to encourage dissemination of the actual information about caffeine, coffee, and related subjects. I think that I’ve forwarded the link to this issue, published May 6, 2010, more than any other link. It’s a remarkable issue and I’ve downloaded all 22 articles just in case the new management ever decides to change access policy.
At the very least, you should read these excerpts from the preface.
Although caffeine is the most widely consumed psychoactive drug worldwide, its potential beneficial effect for maintenance of proper brain functioning has only recently begun to be adequately appreciated. This has mainly resulted from the convergence of conclusions from epidemiological studies and from fundamental research in animal models. Epidemiological studies first revealed an inverse association between the chronic consumption of caffeine and the incidence of Parkinson’s disease; this was paralleled by animal studies of Parkinson’s disease showing that caffeine prevented motor deficits as well as neurodegeneration. Later a few epidemiological studies showed that the consumption of moderate amounts of caffeine was inversely associated with the cognitive decline associated with aging as well as the incidence of Alzheimer’s disease. Again, this was paralleled by animal studies showing that chronic caffeine administration prevented memory deterioration and neurodegeneration in animal models of aging and of Alzheimer’s disease.
Also, from the preface,
Caffeine seems particularly effective to normalize rather than bolstering memory performance and is a candidate disease-modifying agent for Alzheimer’s disease, based on its neuroprotective profile and its ability to reduce amyloid-beta production. Although an inverse relationship between caffeine consumption and neurodegenerative disorders appeared compelling, it was consensual that several methodological issues must be solved before advancing to decisive clinical trials.
Because caffeine is a naturally occurring substance, and therefore can’t be patented, it’s unlikely that anyone will invest the many millions of dollars necessary to get it through the FDA’s drug approval process. Moreover, others have shown that it is difficult to replicate the benefits of coffee using therapeutic caffeine.
The abstract for the chapter titled “Caffeine and Coffee as Therapeutics Against Alzheimer’s Disease“ contains these remarkable words.
Caffeine appears to provide its disease-modifying effects through multiple mechanisms, including a direct reduction of A-beta production through suppression of both beta- and gamma-secretase levels. These results indicate a surprising ability of moderate caffeine intake (the human equivalent of 500 mg caffeine or 5 cups of coffee per day) to protect against or treat AD in a mouse model for the disease and a therapeutic potential for caffeine against AD in humans.
Notice the term “disease-modifying” that means mechanisms of Alzheimer’s are reversed. There is a $6 billion market today for Alzheimer’s drugs that are not disease-modifying. You will hear shortly, however, about a breakthrough drug candidate currently in clinical trials that I believe is disease-modifying.
The chapter titled, “Caffeine, Diabetes, Cognition, and Dementia“ discusses evidence that coffee protect against type 2 diabetes. In fact, there is evidence that coffee protects against other important diseases, including liver and heart diseases, though they are not the focus of theJournal of Alzheimer’s Disease. Incidentally, several articles compare coffee versus caffeine or tea consumption. In some cases, there was no real difference in outcomes. In other cases, however, the combination of the coffee bean and the attendant caffeine seemed particularly effective.
In large part, the JAD issue focused on the need for further research to illuminate how coffee and caffeine work. Since then, however, there’s been really interesting progress.
In particular, I’d like to point out this article, “Caffeine Induces Apoptosis by Enhancement of Autophagy via PI3K/Akt/mTOR/p70S6K Inhibition.” This is not an easy read, but the authors document the role of caffeine in autophagy. Autophagy, as the term implies, is “self eating.” While this may not seem a pleasant process, autophagy is a critical part of cell function. When something in a cell is worn out or flawed, through age or injury, it needs to be consumed and, if possible, recycled.
Obviously, autophagy is related to apoptosis or cell suicide. Once again, it may seem counterintuitive, but cell suicide is our friend. A mutated cell, for example, needs to die and be replaced. Cells that lose the ability to commit apoptosis and die can go on replicating and become cancers.
Apoptosis is a function of the “guardian angel gene,” p53, the master regulator of genomic repair or suicide. All cancers either shut down the p53 gene or block its pathway. Caffeine is a known activator of p53, which may explain some of the health benefits associated with coffee and tea.
As the abstract for this paper in the Journal of Cancer Research states, “The same low concentration of caffeine that was effective for inducing phosphorylation of p53 was also shown to increase p53 activation.”
Moreover, there’s been recent interest in the life-extending benefits, in animals at least, of clearing out senescent or worn-out cells. We don’t know if the same longevity benefits will accrue to humans, but there’s some reason to believe that some of caffeine’s benefits come from its newly discovered ability to increase autophagy.
Autophagy is also a response to calorie restriction, which is the only proven life-extension strategy thus far. Even in primate studies, calorie restriction with optimal nutrition (CRON) produces health benefits.
Of course, CRON also makes most people incredibly and permanently hungry, which means that there will probably never be any real long-term human studies. There are people who can cut calorie intake to the bare minimum for life, but they are rare. This is why indications that caffeine is a p53 activator are great news.
Fortunately, it is not the only way to induce the effects of CRON without actually being hungry (and probably irritable). Several mitochondrial enhancers seem to replicate the winter or calorie-restricted states in animals and this is one of the hottest areas in academic research right now. Based on pretty compelling data, I’m taking one of these compounds, which I’ll get to another time. It increasingly appears, however, that the optimal way to take a mitochondrial-enhancing compound may be with your morning coffee.
One last thing; some people can drink a lot of coffee and some cannot, due to differences in our genomes. I’ve had my genome analyzed by some of the best scientists in this area so I know that I have none of the genotypes that are known to cause adverse reactions to caffeine. This may not be true for you. My wife can only drink moderate levels of coffee before it interferes with her sleep.
I’d like to tell you to talk to your geneticist, but that probably won’t be practical for a year or two while a company I’ve written about inTransformational Technology Alert escalates their operations. In the meantime, use discretion based on your own experiences and talk to your doctor if he/she is keeping up with the literature.
Sincerely,
Patrick Cox
From the TransTech Digest research team: To learn the name of the company covered in Transformational Technology Alert that has a p53-activating drug candidate in development, click here to begin a risk-free trial to Patrick’s elite-level research advisory.
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Picture of coffee by LoboStudioHamburg at Pixabay.
