Balancing Lifestyle Medicine and Pharmacotherapy

Shared decision-making doesn't mean encouraging patients to take the path of least resistance. Prescribing lifestyle changes may not put a smile on their faces, but the long-term benefits often outweigh the risks of lifelong dependence on prescription medication.

By Paul Cerrato, senior research analyst and communications specialist, Mayo Clinic Platform and John Halamka, M.D., president, Mayo Clinic Platform

Our new book, Redefining the Boundaries of Medicine, encourages clinicians to "color outside the lines." Unfortunately, many of us continue to draw inside the lines. When an overweight patient with Type 2 diabetes presents, we typically suggest weight loss but all too often turn to the prescription pad and order metformin to lower blood glucose levels. While there's undoubtedly a place for antihyperglycemic agents in the management of the disorder, the decision to use them should be taken seriously, and clinicians should encourage their use slowly. 

We have entered the era of shared decision-making in medicine, which improves the patient/doctor relationship in many ways. However, sharing decision-making doesn't exclude the value of gentle persuasion. It is a powerful tool clinicians can use to nudge patients toward the optimal treatment regimen. Depending on the relationship one has with a patient, it may be wise to discuss adverse effects in detail in the hope that they will make a greater effort to adhere to lifestyle measures.

Metformin, for instance, can cause diarrhea, bloating, stomach pain, indigestion, constipation, heartburn, headache, skin flushing, nail changes, and muscle pain. Long-term use also has the potential to bring on vitamin B12 deficiency, especially in dosages at or above 1,500 mg per day.1 Depending on how long the deficiency is allowed to linger, it can result in mild to moderate signs and symptoms like fatigue during exertion, skin pallor and other evidence of megaloblastic anemia, or advanced neurological problems, including progressive demyelination, with accompanying peripheral neuropathy, loss of reflexes, and loss of vibratory sense.

Concerns about the risk of metformin-induced vitamin B12 deficiency are not theoretical. When investigators with the Diabetes Prevention Program/DPP Outcomes Study evaluated over 1,000 patients on 850 mg of the drug and compared them to about 1,000 controls over several years, they found B12 anemia linked with long-term use of the medication.2

Like diabetes, cardiovascular disease (CVD) responds well to nutritional therapy and other lifestyle modifications. The support for this approach is based on several evidential pillars, including epidemiological studies, clinical trials, animal research, and investigations that have explored pathophysiology and mechanism of action.

Sebastian Brandhorst and colleagues from the University of Southern California explain, for instance, that chronic inflammation is one of the key mechanisms that put people at risk of CVD, and summarize dietary regimens that address this contributing cause: "Systemic inflammation is one of the important risk factors for CVDs. The high consumption of vegetables, fruits, grains, nuts, healthy oils, fish, and some bioactive components, such as polyphenols, in Mediterranean diet-like patterns are associated with anti-inflammatory properties. However, certain fruits, vegetables, and grains can also have proinflammatory properties."3 A meta-analysis of nine prospective studies involving about 135,000 subjects found that a proinflammatory diet increased the overall risk of dying by 22% and cardiovascular deaths by 24% compared to a low-inflammatory diet.

Clinical trials have likewise supported the value of anti-inflammatory diets. When approximately 7,500 subjects between the ages of 55 and 80 who were at risk of cardiovascular disease were put on a Mediterranean diet supplemented with 50 g of olive oil or with 30 g of mixed nuts, they fared much better than those on a control diet. Subjects who supplemented with olive oil were 31% less likely to develop myocardial infarction, stroke, or die over a 5-year period; those on nuts had a 28% lower risk of the same outcomes.3

Patients need to weigh the benefits and effort of this nutritional approach against those involved in choosing pharmacotherapy. Adhering to a heart-healthy regimen is obviously not the path of least resistance, but eating whatever one wants, in whatever quantities one wants, while taking a statin to lower serum cholesterol, is not the optimal approach to preventing or treating CVD. Some clinicians will start statins without first considering the importance of lifestyle modification. However, when lifestyle alone doesn't work, considering medication is reasonable.

A discussion on the disadvantages of pharmacotherapy, when compared to lifestyle management, does not imply our opposition to the former but only serves to emphasize the fact that many commonly used medications do not restore normal biochemical functioning or homeostasis; they alter normal functioning to produce their therapeutic effects. Sometimes that's the only way to relieve patients' suffering. But sometimes, we must move outside the box and challenge patients to take a more holistic, functional approach. 


1 Kim J, et al. Association between metformin dose and vitamin B12 deficiency in patients with Type 2 diabetes. Medicine. 2019;98:e17918.

2 Aroda V, et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101:1754-1761.

3 Brandhorst S, Lango V. Dietary Restrictions and Nutrition in the Prevention and Treatment of Cardiovascular Disease. Circ Res. 2019;124:952-965

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