Adapted from the Integria Practitioner seminar “Cardiometabolic Health: Underlying Network Mechanisms”

The microbiome can impact cardiometabolic health in unexpected ways. This case explores the links between high dietary protein intake, dysbiosis, uremic toxins and cardiovascular risk.

Initial Consultation

A male patient in his mid-20’s presented with gastrointestinal discomfort, bloating, gas and flatulence, and faecal urgency particularly in the morning. He was also experiencing high levels of stress. He generally had a healthy lifestyle with high exercise levels, as he was a competitive body builder. His diet was clean with minimal processed foods however it was very high in animal protein, with three to four serves of meat daily. Blood tests revealed elevated blood urea of 8.4 nmol/L (normal range 2.3-7.6 nmol/L). All other results were normal.

Elevated blood urea can occur because of a high protein diet, particularly when that protein is animal-derived.¹ In the liver, excess protein is metabolised to nitrogen, then ammonia and finally to urea for excretion.² Elevated blood urea levels are associated with a significantly increased risk of cardiovascular disease, independent of other risk factors.² This could be indicative of impaired renal function,² or due to direct oxidative damage, inflammation and endothelial dysfunction induced by elevated serum urea.¹ Additionally, microbial fermentation of dietary protein in the gut by a dysbiotic microbiome creates high levels of uremic toxins, including trimethylamine N-oxide (TMAO). TMAO is produced via fermentation of animal proteins by several human gut microbes. High circulating levels of TMAO are also associated with a significantly increased risk of cardiovascular events and mortality.² Serum urea is readily available on standard blood tests, and may be a more convenient marker of cardiac risk than serum TMAO.

Prescription

- Dietary changes: Moved to a predominately plant-based diet, reducing red meat  
  intake from twice per day down to twice per week.

Reducing red meat intake will reduce serum urea and TMAO levels in two ways: by reducing the amount of animal protein available for microbial fermentation,³ and by altering the makeup of the microbiome to contain fewer TMAO-producing organisms via the addition of plant fibre.⁴

- St Mary’s Thistle tablets, 1 tablet daily: Silybum marianum dried seed 14.7 g

- Wired and Tired tablets, 2 tablets twice daily: Withania somnifera root dry
  950 mg, Glycyrrhiza glabra root dry 750 mg, Scutellaria lateriflora root dry
  470 mg, Panax ginseng root dry 100 mg

- Probiotic capsule, 1 capsule twice daily: Lactobacillus acidophilus 11.5 billion
  CFU, Bifidobacterium lactis 11.5 billion CFU, Lactobacillus rhamnosus
  2 billion CFU

Follow Up- 8 Weeks

The patient was very compliant with the dietary changes, and with the prescribed supplements. His gastrointestinal symptoms had improved significantly, and he was feeling generally well, though still quite stressed. His prescription was as follows:

- Maintain a plant-based diet

- Continue Wired and Tired tablets, 2 tablets daily

- Cease St Mary’s Thistle tablets and Probiotic capsule

Follow Up – 4 Months

The patient had continued with the plant-based diet, with good compliance throughout this time. He had adjusted well to the increased fibre, and had managed to maintain adequate protein from plant-based sources. This was very important to him as a body builder, and he was pleased to see no negative impact on his strength and muscle mass from the reduction in meat consumption. His gastrointestinal symptoms had all resolved. Follow up blood tests revealed that his serum urea levels had returned to the normal range, at 6.6 nmol/L (normal range 2.3-7.6 nmol/L).

Clinical Thoughts

This case highlights the fact that a client can be eating “clean” and exercising regularly, yet still have the beginnings of cardiometabolic dysfunction. Serum urea levels are readily available through standard blood tests, and may serve as a ‘silent marker’ of cardiovascular risk, allowing clinicians to identify early cardiometabolic dysfunction years before clinical symptoms occur. The microbiome can alter the way particular foods such as protein affect our health, and plays an important role in cardiovascular health. Modulating the microbiome through probiotics, fibre and dietary changes can have far-reaching effects on our clients’ long-term cardiovascular health.

This case has been adapted from the Integria Practitioner seminar “Cardiometabolic Health: underlying network mechanisms” with dr elizabeth steels and emma van den driest. to learn more about how Innovative cardiometabolic plasma markers can detect disruptions to the metabolome and microbiome years before clinical manifestation of disease, register at https://practitioner.integria.com/events/cardiometabolic-health-underlying-network-mechanisms

References

1. Ko GJ, Rhee CM, Kalantar-Zadeh K, Joshi S. The effects of high-protein diets on kidney health and longevity. Journal of the American Society of Nephrology [Internet]. 2020 Aug 1 [cited 2023 May 8];31(8):1667–79. Available from: /pmc/articles/PMC7460905/

2. Hong C, Zhu H, Zhou X, Zhai X, Li S, Ma W, et al. Association of Blood Urea Nitrogen with Cardiovascular Diseases and All-Cause Mortality in USA Adults: Results from NHANES 1999–2006. Nutrients 2023, Vol 15, Page 461 [Internet]. 2023 Jan 16 [cited 2023 May 8];15(2):461. Available from: https://www.mdpi.com/2072-6643/15/2/461/htm

3. Qi J, You T, Li J, Pan T, Xiang L, Han Y, et al. Circulating trimethylamine N-oxide and the risk of cardiovascular diseases: a systematic review and meta-analysis of 11 prospective cohort studies. J Cell Mol Med [Internet]. 2018 Jan 1 [cited 2023 May 8];22(1):185–94. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.13307

4. Mitchell SM, Milan AM, Mitchell CJ, Gillies NA, D’souza RF, Zeng N, et al. Protein Intake at Twice the RDA in Older Men Increases Circulatory Concentrations of the Microbiome Metabolite Trimethylamine-N-Oxide (TMAO). Nutrients 2019, Vol 11, Page 2207 [Internet]. 2019 Sep 12 [cited 2023 May 8];11(9):2207. Available from: https://www.mdpi.com/2072-6643/11/9/2207/htm

5. Wiese GN, Biruete A, Moorthi RN, Moe SM, Lindemann SR, Hill Gallant KM. Plant-Based Diets, the Gut Microbiota, and Trimethylamine N-Oxide Production in Chronic Kidney Disease: Therapeutic Potential and Methodological Considerations. Journal of Renal Nutrition. 2021 Mar 1;31(2):121–31.