Page 39 - Today's Dietitian (February 2020)

says that lowering TMAO in those women wouldn’t
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lower cancer risk. “TMAO might be a great marker
for a disrupted gut microbiome, or maybe a marker
of greater kidney dysfunction than we thought,”
Caudill says. “Then we could start treating the
actual problem.”
Determining the exact relationship between
diet, gut microbes, and disease endpoints will
be challenging, but it’s likely an important step
in determining who—if anyone—might benefit
from nutritional or pharmaceutical interventions
to reduce TMAO production. In rats, a high-salt diet
can increase plasma TMAO levels, decrease TMAO
25
excretion in urine—and alter the gut microbiota. On
the pharmaceutical front, the TMAO synthesis pathway
has become one of the first gut microbiota targets for drug
14
intervention to prevent CVD.
Individual genetic variation also may play a role in elevated
TMAO levels by increasing enzymatic conversion of TMA to
TMAO in the liver by flavin-containing monooxygenases (FMOs).
Humans have five FMO genes—and five FMO enzymes—but it’s “We know very well within the RD world that science continues
the conversion of TMA to TMAO by FMO3 that may be a culprit to support the importance of consuming seafood at least twice
in atherosclerosis and CVD. Several factors can increase FMO3 a week in a healthy diet.”
gene expression—estrogen and insulin increase it, while testos-
terone and glucagon repress it. Notably, FMO3 expression is ele- Bottom Line for RDs
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vated in individuals with type 2 diabetes. What’s more, FMO3 If it’s unclear which individuals may benefit from TMAO-lowering
may have adverse effects on blood lipids and glucose indepen- strategies, how can dietitians counsel their clients who have
dently of TMAO formation, although more research is needed. 13,26 concerns?
“I think it’s extremely important to always validate a client’s
Public Health Recommendations fears and help them recognize a safe and effective approach to
Some research studies that have found associations between rationally treating those fears,” Shaw says. Shaw adds that she
TMAO levels and CVD have gone so far as to recommend lim- thinks there’s enough evidence to support continuing to include
iting or avoiding choline-rich foods and dietary supplements foods that naturally may contain TMAO or potentially produce
containing choline. Caudill says this isn’t only premature, but TMAO. “No one food (or compound) is going to be the trigger;
it’s concerning, because following that advice may have unin- it’s their environment, genetics, lifestyle, and nutrition plan that
tended consequences. “The demand for choline is so high,” she will have the biggest impact on their total health.”
says, adding that there’s evidence that going above the AI may Clients who regularly eat eggs and meat tend to get enough
be beneficial in certain populations, while other populations choline in their diets, but vegans—and vegetarians who avoid
may need to be cautious about supplementing with both choline eggs—need to be more thoughtful about meeting the AI. Con-
and folic acid, which can increase cell division. But this requires suming foods such as Brussels sprouts, broccoli, cauliflower,
a nuanced therapeutic approach, not a sweeping public health soymilk, wheat germ, peanuts, and beans can help, but supple-
recommendation. mental choline may be needed to make up shortfalls.
“If you want to go that route, you would have to tell people to Shaw says she often recommends helping clients take steps to
reduce their intake of fish,” Caudill says. “You may even have to improve the balance of their gut microbiota through their food
tell people to eliminate fish.” choices, rather than cutting out choline-rich foods such as fish
It’s a conundrum that many fish species contain both TMA or eggs. If kidney function is impaired, or insulin resistance is
and TMAO. Fish intake acutely raises TMAO levels, yet fish is present, she says appropriate medical and dietary therapies are
a significant component of the Mediterranean diet and inde- the logical place to start.
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pendently has been shown to benefit cardiovascular health. A “We have to show that lowering TMAO levels in blood shows
small 2017 study using participants in the larger European Pro- benefit,” Caudill says. Then, she says, we might intervene, with
spective Investigation into Cancer and Nutrition trial to iden- drugs that interrupt the choline-TMA-TMAO pathway, by altering
tify blood markers of intake of various foods—for potential use the microbiota, or by altering nutrition. “Right now, there is just
in epidemiologic studies—found that TMAO was a good blood no good evidence that in humans elevated TMAO is doing harm.”
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marker of intake of both lean and fatty fish. One 2017 study on
healthy young men found that blood levels of TMAO were about Carrie Dennett, MPH, RDN, CD, is the nutrition columnist for The
50 times higher after consuming fish than they were after con- Seattle Times, owner of Nutrition By Carrie, and author of Healthy
suming eggs or beef. for Your Life: A Holistic Guide to Optimal Wellness.
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Liz Shaw, MS, RD, CLT, CPT, San Diego–based owner of Shaw’s
Simple Swaps and a spokesperson for choline, says it’s important For references, view this article on our
for dietitians to explain what TMAO really is, where it’s found, website at www.TodaysDietitian.com.
and what its uses are to demystify some of the headline hype.
FEBRUARY 2020 • WWW.TODAYSDIETITIAN.COM 39