Now that we’ve examined all three elements of the ADAPT Framework—Functional Medicine, an ancestral diet and lifestyle, and a collaborative practice model—I’d like to address the question of evidence. We often hear the claim that conventional medicine is “evidence-based,” whereas approaches like Functional Medicine and an ancestral diet and lifestyle are not. But is this true? Let’s take a closer look.
Is Conventional Medicine Evidence-Based?
“It is simply no longer possible to believe much of the clinical research that is published,” says Marcia Angell, a former editor of the New England Journal of Medicine (Full Measure Staff 2017). She should know! John Ioannidis, an influential researcher from Stanford, published the 2005 paper, “Why Most Published Research Is False,” to illuminate this problem (Ioannidis 2005). Ioannidis explains that in many research papers, “Claimed findings may be accurate measures of the prevailing bias.” Clearly, Dr. Ioannidis struck a nerve; this paper is now the most widely cited paper ever published in the journal PLoS Medicine.
In other words, most published research findings support the status quo; they’re not necessarily based on solid evidence. Often, the research that builds on an initial study ends up perpetuating questionable findings. It’s like building a house of cards: a paper gets published that references another paper; then, a third paper gets published that references that second paper, which referenced that first paper, and so on. The assumption is that the evidence in that first paper was correct—but what if it’s not? The edifice of peer-reviewed research is not as perfect as we tend to believe.
Conflicts of interest abound: two-thirds of medical research is funded by pharmaceutical companies (Smith et al. 2014). Such financial ties don’t guarantee bias, but they do make it more likely. As Upton Sinclair once said, “It’s difficult to make a man understand something when his salary depends upon him not understanding it.” Sinclair wasn’t just imagining this. Studies have repeatedly found that industry-sponsored trials are more likely to report favorable results for drugs because of biased reporting, biased interpretation, or both (Lexchin 2003). The time-honored saying, “Don’t bite the hand that feeds you,” also applies.
Another problem is that conflicts of interest in academic research are rarely disclosed. A 2009 report issued by the Department of Health and Human Services showed that very few universities required reports to be made to the government about their researchers’ financial conflicts of interest (Levinson 2009). Even when they are reported, the universities rarely require those researchers to eliminate or reduce those conflicts. In fact, 90 percent of universities relied solely on the researchers themselves to decide whether to report their potential conflicts of interest. Half of universities don’t ask their faculty to disclose the amount of money or stock they earn from drug or device makers. True objectivity in scientific research is not as common as we think.
Conflicts of interest aren’t just a problem in academia, they’re also a problem on advisory panels that influence health policy. In 2008, it was found that eight out of nine of the experts who were responsible for writing the National Cholesterol Education Program Guidelines had ties to statin drug manufacturers (Kresser 2015). Dr. Stephan Guyenet reported in 2008 (Guyenet 2008) that one of the study’s authors had, “received honoraria from Merck, Pfizer, Sankyo, Bayer, Merck/Schering-Plough, Kos, Abbott, Bristol-Myers Squibb, and AstraZeneca.”
Fraud is also an underappreciated problem in medical research, both intentional and unintentional. Consider a recent paper called “Out of Sight, Out of Mind, and Out of the Peer-Reviewed Literature,” published in JAMA Internal Medicine (Seife 2015). The study notes that the FDA’s findings of fraud in medical research rarely end up being reported. The studies are still published. In this investigation, a researcher falsified a lab test to hide a patient’s impaired kidney and liver function in a trial comparing two chemotherapy regimens. The first dose of the regimen proved to be fatal to that patient, and the researcher was ultimately sentenced to seventy-one months in prison. That episode was described by both the FDA and in court documents, but not one of the studies on the chemotherapy trial reported in the peer-reviewed literature made any mention of the falsification of data, the fraud, or thehomicide.
INTERVENTIONS WITHOUT EVIDENCE
Many common interventions within conventional medicine are not supported by solid evidence.
Abilify, for example, is one of the best-selling drugs in the United States. It was originally developed as an anti-psychotic, and is approved for schizophrenia, bipolar disorder, depression, and autism spectrum disorders.
The two previous sentences, when taken together, should raise some questions. How could Abilify be one of the best-selling drugs in the country if it’s only being used as an anti-psychotic? How many people in this country need an anti-psychotic drug?
Quite a few, it seems. This anti-psychotic drug is now being used for anxiety, ADHD, depression, insomnia, OCD, and to treat all kinds of substance abuse. In fact, 77 percent of the prescriptions given for Abilify are for off-label conditions, meaning there’s no evidence supporting the drug’s efficacy in treating those conditions. There is also no peer-reviewed scientific evidence to support these uses of Abilify.
The numerous patients taking this drug might experience a wide range of concerning side effects, including weight gain, blurred vision, nausea, vomiting, changes in appetite, constipation, drooling, headache, dizziness, drowsiness, anxiety, sleep problems, and cold symptoms like stuffy nose, sneezing, and sore throat. Yet despite these numerous side effects, and the drug’s insubstantial evidence—it continues to be prescribed.
We might hope that the recommendations coming out of conventional medicine offices are all grounded in objective, evidence-based research, but that simply isn’t the world we live in.
Functional Medicine’s Evidence-Based Approach
In Functional Medicine, we emphasize the importance of evidence-based interventions. If a Functional Medicine clinician tells patients to reduce their exposure to artificial light to help manage their stress, reduce their risk of disease, or even address issues like diabetes and obesity, that’s because there’s research that supports that connection. We’re wary of trends that have no substantial research to back them up.
On the other hand, we also tend to consider new information and methods that are verifiable from evidence earlier than in conventional medicine. Intestinal permeability, or “leaky gut,” is a case in point. Twenty-five years ago, the best way to get yourself laughed out of a room full of doctors would have been to start talking about leaky gut—it was considered the realm of alternative quacks. When searching the scientific literature today, the term “intestinal permeability” brings up thousands of articles. Intestinal permeability has been linked to autoimmune disease, diabetes, and depression; certainly, it’s a legitimate medical issue that warrants treatment. What seems controversial today may not be so in ten years as new research emerges.
Stomach ulcers are another example. For decades, physicians believed they were caused by stress and perhaps overconsumption of certain foods. Treatment was based on avoiding spicy foods and vague recommendations to manage stress. Then, in the early 1980s, two Australian physicians, Dr. Barry Marshall and Dr. Robin Warren, introduced the idea that ulcers were not caused by stress, but by an infection with a spiral bacterium called Helicobacter pylori. Initially, Drs. Marshall and Warren were ridiculed for their unorthodox theory. In fact, it wasn’t until Dr. Marshall purposely infected himself with H. pylori, developed an ulcer, and then successfully treated it with antibiotics that the scientific community took notice. Even then, more than a decade passed before this new theory became widely accepted, and it wasn’t until Drs. Marshall and Warren won the Nobel Prize for Medicine in 2005 that the importance of their discovery was fully acknowledged.
In a hundred years, medical practitioners will probably shake their heads over the methods used today. After all, nobody today would treat a headache by drilling a hole in a patient’s head, but that was the practice in the Dark Ages. In fact, it’s not an exaggeration to say that the history of science has been the history of most people being wrong about most things most of the time. The willingness to challenge even our most deeply held assumptions, and the humility to admit when we’ve been wrong, are essential to good science. Unfortunately, in the conventional medical paradigm, this willingness and humility have often been replaced by groupthink, arrogance, and a stubborn attachment to the status quo.
In Functional Medicine, we recognize the importance of diagnoses and treatments that are supported by peer-reviewed evidence published in reputable scientific journals. At the same time, we also recognize the real limitations and biases of this research, and we remember that today’s heresy may end up being tomorrow’s orthodoxy. Therefore, we ground our treatment recommendations both in research and open-mindedness.
Even when we recognize the limits of current research into medicine of any kind, we still ask, what does the research say about Functional Medicine? It’s not always easy to tell. Often, Functional Medicine’s results are invisible in the scientific literature. Research is conducted in the conventional paradigm of symptom-driven intervention. If you were to search the scientific literature for IBS, for example, you would see several studies supporting the use of Imodium to stop diarrhea; that’s symptom-driven research. It would be easy to conclude that Imodium is the best way to treat IBS, even when it isn’t.
Functional Medicine is not a symptom-driven model, and doesn’t align readily with symptom-driven research. It’s not hard to show that Imodium stops diarrhea. It’s much more complex to design a study that demonstrates the efficacy of changing a person’s diet, and testing and treating them for SIBO, parasites, or fungal overgrowth. It’s harder to design a study that uses multiple interventions customized for each patient. The gold standard of conventional research—the randomized clinical trial—isolates just one variable, then tests the effect of that variable; all other elements of the study are kept the same. The randomized clinical trial is practically the antithesis of the philosophy of Functional Medicine, which seeks to tailor layered treatment plans to individual patients.
The Literature on Functional Medicine
The research supporting the Functional Medicine approach is out there, if you know where to look. Research connects IBS to parasites, to SIBO, to gut-brain axis dysfunction, and to other underlying causes, but those studies are spread across a wide range of publications. You won’t find a convenient collection of varied studies on a Functional Medicine approach to IBS in one place.
If a doctor is trying to decide how to treat a patient’s IBS, she’ll most likely choose the approach that’s most accessible. As the PubMed results pile up, she might glance down at her desk and see the brochure on IBS a pharmaceutical sales rep left for her to read. The rep had described a new drug that’s been tested and shown to help with IBS, and the brochure lists the latest studies showing the drug’s efficacy and benefits. After a long day, it’s a relief for this physician to exit out of PubMed and head home, assured that she has found an accepted treatment protocol, which won’t require her to scour dozens of individual studies.
Even a better-than-average product like UpToDate (see sidebar) isn’t saying, “Here’s how you look at this disease from a Functional Medicine approach. Here are the other underlying pathologies that can cause it, and here’s how to test for those and treat those.”
Attending conferences and continuing education classes can help doctors stay current, but those conferences are often sponsored by a drug company. Much of the information in continuing education is still driven by a corporation with an agenda. Keep your eyes open and you’ll find substantial research supporting Functional Medicine.
For example, numerous studies substantiate correlations between IBS and SIBO, along with other gut infections (Bowe and Logan 2011; Daniels et al. 2017; Ghosal et al. 2017). Functional Medicine treatments for psoriasis are well supported by research, too; there’s evidence linking skin conditions to changes in gut health and gut flora. Depression has been convincingly linked to systemic inflammation, which in turn is often caused by altered gut microbiota. There is also a vast body of evidence supporting the ancestral diet and lifestyle.
The scientific literature is the most natural place to start when considering new treatments, but it should be tempered with other perspectives as well. Peer-reviewed research is venerated, but in addition to the problems previously addressed, there’s an important issue few consider: In many cases, initial research results are never replicated. The scientific method is based on replicability—when there’s an initial finding, its value depends on it being reproduced by other researchers in other labs. Typically, a finding isn’t considered truly valid until this happens.
Unfortunately, much of the research we’ve formerly relied upon was never replicated. For example, the Open Science Collaboration tried to replicate 100 published psychology studies under conditions identical to the original research, and 65 percent of the studies failed to replicate the results (Open Science Collaborators 2015). The problem is not just in psychology. In 2011, a group of researchers from Bayer looked at sixty-seven blockbuster drug discovery trials published in prestigious journals; they found that 75 percent of them could not be reproduced (Hartung 2013). Another study of cancer research found that only 11 percent of pre-clinical cancer research could be reproduced (Begley and Ellis 2012).
Does this mean we should throw out all published research altogether? No. Research must be our first step in determining treatment, but we should have a healthy degree of skepticism when consulting scientific publications. This skepticism should lead us to think critically about a study. Perhaps we examine the funding behind a study that seems to endorse a new pharmaceutical with particular zeal. A potential conflict of interest doesn’t necessarily mean that the research is invalid, but it’s worth investigating.
Functional Medicine physicians often have more time to do that digging. They see fewer patients and therefore have more space in their schedules, and more time to stay current with research. That’s important because there’s often a big gap between research getting published and when that research trickles down to the practicing PCP. The latest research shows that saturated fat isn’t the boogeyman that we thought it might be, but the average PCP is probably not aware of that. If a doctor finds the most current published peer review research in PubMed and asks his colleague if she’s familiar with the research, the colleague will likely say no. The latest research often takes time to reach practicing clinicians—and their patients.
UPTODATE
Some databases are better than others, but even the best databases serving most conventional doctors maintain a symptom-driven lens.
UpToDate is a more balanced, subscription-based information product for clinicians. If you look up IBS here, you see an entry describing the treatment of IBS in adults, along with an introduction to the condition, definitions, and indications for referral.
UpToDate is unusual in that it does sometimes talk about dietary therapy, though it moves quickly on to pharmacological therapy, laxatives, how to treat diarrhea, how to treat constipation, and how to treat many other symptoms.
Evidence for an Ancestral Diet & Lifestyle
There are numerous studies in the scientific literature supporting all aspects of the ancestral diet and lifestyle, from the benefits of nutrient-dense, whole foods, to the effects of artificial light on circadian rhythms and sleep, to the need for increased non-exercise physical activity, to the connection between stress and disease, to the importance of play, leisure, and social connection. My first book, The Paleo Cure, contains over 350 citations documenting these relationships.
For example, the New York Times recently published an article about the Tsimané (Brody 2017). They’re a subsistence farming and hunter-gather population in Bolivia, who still follow their traditional diet and lifestyle. Researchers went to Bolivia to study heart disease in the Tsimané. They found that the Tsimané’s rate of heart disease is about one-fifth of the rate observed in the United States. Nine in ten tribal members had clean arteries and faced no risk of heart disease. An eighty-year-old in the Tsimané group showed the same vascular age as an American in his mid-fifties (Kaplan et al. 2017).
This is important research; it tells us there’s clearly something about our diet and lifestyle that’s not working. At the same time, it reveals that something about an ancestral diet and lifestyle can help prevent chronic disease (Kresser 2017).
Considering evolutionary alignment is a valid way of generating hypotheses and potentially resolving apparent conflicts in modern research. Consider the Maasai, a tribe in Kenya and Northern Tanzania that gets two-thirds of its calories from fat. They consume 600-2,000 mg of cholesterol a day. In contrast, the American Heart Association (AHA) recommends consuming under 300 mg of cholesterol a day. (As of 2017, the AHA no longer suggests restricting cholesterol intake, due to overwhelming evidence indicating that there is no benefit to doing so.) The Maasai, however, have low blood pressure, low cholesterol, few gallstones, and little atherosclerosis (Bhatia 2012).
If populations like the Maasai achieve low rates of heart disease while eating a high amount of saturated fat, we should question some of our earlier assumptions. A study like this doesn’t disprove that saturated fat increases the risk of heart disease on its own but invites us to ask questions. “Is there a different cause for heart disease in modern populations that we haven’t considered?” People in the United States with higher rates of heart disease appear to be eating more saturated fat, but that doesn’t establish a causal relationship. Maybe there’s something else happening. Maybe people who eat more saturated fat are more sedentary, or smoke more, or something else we haven’t yet considered. Looking through an evolutionary lens raises these questions.
Observational evidence like this should also spur us to critically examine other research on the topic. When we do that in the case of saturated fat and heart disease, the connection is a lot murkier than the AHA would have you believe. Although saturated fat does raise blood cholesterol levels in some studies, it has no effect in many others (Mensink et al. 2003). More importantly, large reviews have found no direct relationship between saturated fat intake and heart disease (Siri-Tarino et al. 2010), and people who eat more saturated fat have lower rates of stroke (Yamagishi et al. 2010). Should we be concerned when saturated fat increases cholesterol if that does not translate into a greater risk of heart disease (and may even reduce the risk of stroke)?
If we look at that data through an evolutionary lens, we’re often given needed perspective to generate new ideas for research. We can compare the claim that dietary fat causes heart disease to the experience of traditional populations like the previously mentioned Maasai. When we do, we find inconsistencies. The traditional population consumes a high intake of dietary fat but experiences no heart disease.
Evidence Supporting a Collaborative Practice Model
In the last chapter, we discussed the importance of a collaborative care model, which includes allied providers like nutritionists and health coaches.
People want to feel good, avoid chronic disease, and live a long life. They want to see their children and grandchildren grow up and have the energy to play with them. They want to perform better at work, enjoy their relationships, and be well enough to get the most out of life. But there’s a big difference between wanting the benefits of being healthy, and consistently engaging in the behaviors that lead to health.
That’s where allied providers like health coaches come in. Coaches are trained in several disciplines that support people in making lasting change. These include (but aren’t limited to):
· Positive psychology, which leverages people’s strengths (rather than focusing on their weaknesses) to make changes.
· Motivational interviewing, which helps people link behavior changes to their deepest needs and goals (e.g., “I will change my diet because I want to live to see my grandchildren graduate from college.”).
· Habit formation and reversal, which supports patients in making positive habits, or breaking negative ones.
Each of these disciplines is supported by significant research. For example, a recent paper called “Effects of Positive Psychology Interventions on Risk Biomarkers in Coronary Patients” found that a positive psychology intervention lowered levels of C-reactive protein, an inflammatory marker, in patients with heart disease (Nikrahan et al. 2016). Another paper found that motivational interviewing increased the efficacy of a weight loss program in a group of overweight and obese women (Mirkarimi et al. 2015). Some research has shown that applying evidence-based principles of behavior change can increase the chances of success by over 1,000 percent (Grenny et al. 2008)!
Coaches are trained to work with patients in a more collaborative way, rather than with the expert approach that is common in medicine. In the expert approach, the “authority” assesses the problem, delivers advice, recommends solutions, and in some cases, teaches new skills. In the collaborative approach, the coach acts as a partner or ally, encourages the client to discover their own solutions and become their own advocate, and supports them in developing the skills they need to embrace new behaviors.
This collaborative approach empowers the client to become the primary driver of change. It also builds confidence, self-awareness, and self-actuation—all of which are crucial for long-term change, since the client will likely not work with the coach for the duration of his or her lifetime. To use an analogy, the doctor gives the patient a fish so she can eat for a day, whereas the coach teaches the client to fish so she can eat for a lifetime.
This more collaborative approach is also evidence-based: studies have consistently shown that coaching interventions improve health outcomes for several chronic diseases, including obesity (Appel et al. 2011), diabetes, heart disease, and cancer (Butterworth et al. 2006).
Anecdotal Evidence: The Importance of Clinical Experience
Another valuable trove of data comes from the anecdotal evidence doctors collect from working with patients. Anecdotal evidence is not reliable on its own, but it shouldn’t be dismissed outright. Case studies can prompt new hypotheses and testing. Even when a treatment shines in a randomized clinical trial, it may be problematic in practice. Many patients experience side effects that people in the original study didn’t—perhaps because there was a fluke in the research process or maybe because the side effects weren’t reported. Evidence collected by interacting with patients is invaluable: it relates to real patients having real symptoms and can confirm or question the originalresearch.
I might introduce a patient to a new treatment that looks promising in the literature and watch carefully for neutral or negative results. If it doesn’t work, or causes side effects, I’ll revise my assessment of that treatment’s efficacy and change my patients’ recommendations accordingly. For example, several studies suggest that colostrum can be beneficial for a wide range of GI conditions, but my patients haven’t experienced much success with it. That doesn’t mean that it’s not useful—perhaps other clinicians or another set of patients would experience greater success—but my anecdotal experience would lead me to pursue other options with my patient population.
“Evidence-based research” turns out to be more of a loaded term than we may have initially guessed.