Plant Based and Mediterranean Diets Strengthen Microbiome and Create Protection Against Heart Disease: A Stanford Study
Gut microbiome, diet and health
Few novel scientific fields have captured the imagination of the public as much as the gut microbiome. Every week new evidence emerges of how the microorganisms living in our gut affect human health, from type 2 diabetes to depression. In turn, our behavior can affect our gut microbiome, from medication use to diet. One of the first major studies to highlight the impact of diet on the gut microbiome was a 2014 paper by Peter Turnbaugh’s group out of Harvard University. The authors presented how even four days on a plant-based or animal-based diet led to a rapid change in gut microbiome communities of the participants. Interestingly, the gut microbiome of the animal-based diet participants showed an increase in metabolism of specific bile acids associated with promotion of liver cancer, with an increased ability to make enzymes that have been associated with inflammatory bowel disease. The animal-based diet also promoted the growth of B. wadsworthia, a bacteria associated with induction of metabolic dysfunction.
What role does the gut microbiome play in cardiovascular disease?
In fact, evidence of how animal-based diet, mainly high red meat consumption, is detrimental to human health is mounting. Frequent red meat consumers had three times the risk of developing cardiovascular disease compared to those consuming a plant-based diet (Wang et al. 2018). One component driving this increased risk is called trimethylamine N-oxide (TMAO), a molecule known to increase inflammation, increase platelet hyperactivity, and reverse cholesterol transport, together increasing the risk of heart failure, stroke, and heart attack (Tilg, 2016). Patient plasma TMAO is a predictor of adverse cardiovascular events, even after adjustment for traditional risk factors (like diabetes, cholesterol levels, smoking status) (Tang et al. 2013; Tang et al. 2014). Diets high in red meat have been associated with high TMAO levels, driven by the gut microbiome metabolizing nutrients like phosphatidylcholine, choline, and carnitine found in red meat into trimethylamine (TMA), later converted by the liver into TMAO (Janeiro et al. 2018).
Are plant-based alternatives better?
Limiting red meat consumption is key to decreasing cardiovascular risk. The most well-established alternative is a plant-based diet, which can be challenging for a market palate and culture focused around meat consumption. Plant-based meats are a proposed common good alternative, now found widely across grocery stores in the United States. However, most of these alternatives meet the NOVA definition of ultra-processed foods (Monteiro et al. 2018), consumption of which has been associated with increased risk of weight gain, obesity, and associated non-communicable diseases such as type 2 diabetes (Srour et al. 2020). Additionally, they tend to be as high as red meat in sodium and saturated fat. NOVA is a system that classifies food products according to how they’ve been processed, whether that’s biologically, physically, or chemically.
Could plant-based meat alternatives decrease cardiovascular risk?
In 2020, the Sonnenburg Lab and Gardner Lab, both out of Stanford University collaborated on this exact question. They performed a randomized crossover trial, named SWAP-MEAT (The Study With Appetizing Plantfood— Meat Eating Alternatives Trial). In the trial, 36 participants were randomized into one of two groups. The first group was directed to consume two or more servings of red meat a day for eight weeks total (referred to as the ‘Animal phase’), limiting the amount of other meats like fish or white meat. After eight weeks, this group was directed to switch to consuming the same serving size of plant-based meat (provided by Beyond Meat) for an additional eight weeks, and referred to as the ‘Plant phase’. The second group did the opposite, starting with the Plant phase, and switching to the Animal phase after eight weeks. All participants had to keep a strict log of their dietary habits, and fasting blood samples were collected from each participant every two weeks.
Plant-based meat alternatives do not increase TMAO levels
Participants were able to maintain their selected diets for the entirety of the sixteen weeks, consuming comparable amounts of animal derived meat to plant-based meats. As expected, sodium, saturated fats, and protein intake was about the same at both phases, while fiber intake decreased during the Animal phase compared to the Plant phase, given Beyond Beef products contain added dietary fiber. In addition, low-density lipoprotein (LDL) cholesterol (commonly referred to as “bad” cholesterol) and weight of participants were significantly lower following the Plant phase when compared to the Animal phase. As might have been hypothesized, TMAO, our cardiovascular risk marker, was significantly lower in the Plant phase compared to the Animal phase. Of special note, however, the order in which participants completed the Plant or Animal phase mattered to their TMAO levels. The first group, assigned to the Animal phase first, showed a decrease in mean TMAO following the switch to Plant phase. The second group would be expected to show the opposite effect: an increase in mean TMAO following transition from the Plant phase to the Animal phase. However, what the researchers observed was no change in mean TMAO. They interpreted these results as a potential microbiome effect — the Plant phase adapted microbiome may provide a protective effect against TMA production (and thus TMAO production).
What does this mean for meat alternatives?
While this study was small, the significant difference in TMAO is promising when it comes to making dietary recommendations to decrease cardiovascular risk markers. Not only would a shift away from red meat consumption to plant-based meat provide benefits to individual health, but plant-based options offer an environmentally sustainable option. On the other hand, while LDL cholesterol and weight also decreased in participants during the plant-based meat alternative phase, the health impact of ultra-processed foods should not be dismissed, as this study only monitored for cardiovascular risk. There are two potential solutions to striking a balance between decreased cardiovascular risk and limiting ultra-processed food consumption. First, one way of interpreting this study is that not eating meat allows for the gut microbiome to protect against TMAO production, and occasional meat consumption might be just as cardiovascularly healthy as no meat consumption. From a sustainability standpoint, while decreasing meat consumption is key, removing meat as a dietary option would be best. Another solution may be driven by cellular agriculture. Could lab grown meat be made without TMAO precursors? The future could hold meat created without ultra-processed ingredients, while satisfying the perfect balance of cardiovascular health and environmental sustainability.
References
Crimarco, Anthony, et al. "A randomized crossover trial on the effect of plant-based compared with animal-based meat on trimethylamine-N-oxide and cardiovascular disease risk factors in generally healthy adults: Study With Appetizing Plantfood—Meat Eating Alternative Trial (SWAP-MEAT)." The American journal of clinical nutrition 112.5 (2020): 1188-1199.
Janeiro, Manuel H., et al. "Implication of trimethylamine N-oxide (TMAO) in disease: potential biomarker or new therapeutic target." Nutrients 10.10 (2018): 1398.
Koeth RA, Lam-Galvez BR, Kirsop J, Wang Z, Levison BS, Gu X, Copeland MF, Bartlett D, Cody DB, Dai HJ, et al. l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. J Clin Invest 2018;129(1):373–87.
Monteiro, Carlos Augusto, et al. "The UN Decade of Nutrition, the NOVA food classification and the trouble with ultra-processing." Public health nutrition 21.1 (2018): 5-17.
Srour, Bernard, et al. "Ultraprocessed food consumption and risk of type 2 diabetes among participants of the NutriNet-Santé prospective cohort." JAMA internal medicine 180.2 (2020): 283-291.
Tang, WH Wilson, et al. "Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk." New England Journal of Medicine 368.17 (2013): 1575-1584.
Tang, WH Wilson, et al. "Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease." Circulation research 116.3 (2015): 448-455.
Tilg, Herbert. "A gut feeling about thrombosis." New England Journal of Medicine 374.25 (2016): 2494-2496.
Wang, Zeneng, et al. "Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women." European heart journal 40.7 (2019): 583-594.
Written for Helikon by Elisa Caffrey, Guest Author and Stanford PhD Candidate
