SOY FOODS WARRANT INCLUSION IN THE DIETS OF PATIENTS USING GLP-1 RECEPTOR AGONISTS

By Mark Messina, PhD, MS

The advent of the new generation of anti-obesity medications such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has ushered in an exciting era in weight management. While caloric restriction combined with exercise remains a widely preferred approach to weight loss, maintaining significant results over time can be challenging with traditional lifestyle measures alone. Nevertheless, patients using GLP-1 RAs still need dietary counseling because the nutrient density of the diet needs to be so much higher. The appetite suppression that occurs in patients using GLP-1 RAs means nutrient needs have to be met in far fewer calories. 

The need for patients to consume protein in amounts exceeding the RDA to slow the loss of muscle mass that occurs with weight loss is a much discussed topic.¹ Estimates of the loss of muscle mass in response to GLP-1 RA use range from 25% to almost 40%, although it is not yet clear whether these drugs cause more loss than other approaches resulting in similar weight loss such as bariatric surgery.² 

There are many options for increasing protein intake, but soy foods have advantages compared to most. For one, the quality of soy protein is greater than that of nearly all other plant proteins.3 It is on par with animal protein, but soy foods don’t provide the amounts of saturated fat common to animal sources. For this reason, and because soy protein directly lowers blood cholesterol levels,^4,5 soy foods may help boost the recently observed cardiovascular benefits of GLP-1 RAs. 

In a multi-centered trial involving over 17,000 patients with preexisting cardiovascular disease, in comparison to the placebo, semaglutide reduced risk of a primary cardiovascular endpoint (a composite of death from cardiovascular causes, nonfatal myocardial infarction) by 20%.⁶ However, semaglutide reduced LDL-cholesterol by only about 2% relative to the placebo. Adding soy foods to the diet may improve upon that. Whether soy foods can enhance the hypotensive effects of semaglutide is an interesting question given recently published research.⁷

There are several side effects associated with GLP-1 RA use, especially during the dose escalation phase.⁸ One of these is constipation, at least in a subset of patients. Therefore, higher fiber foods may be helpful. To get both protein and fiber, soy foods such as whole soybeans, edamame, and soy nuts come to mind. Conversely, some patients report having diarrhea, which suggests that high-fiber foods should be avoided. In this case, soy foods such as tofu and soymilk fit the bill. Tofu also has a neutral flavor, which is an attribute that many patients may find appealing given that their taste preferences may have been altered.

Furthermore, consuming tofu and soymilk that are calcium-fortified can help to meet the need for this mineral. Although many plant-based milk alternatives are fortified with calcium, relatively few provide the amount of protein soymilk does. And most importantly, calcium absorption from these soy foods is similar to the absorption of calcium from cow’s milk.^9,10 Little is known about the bioavailability of calcium from non-soy plant-based milk alternatives. 

Concentrated forms of soy protein, such as soy protein isolate, are also a good choice.  They provide protein without fiber and can be added to a range of products such as beverages, bars, and breakfast cereals, which makes it quite easy to incorporate them into the diet. An additional advantage is that patients can decide portion sizes for themselves as smaller meals are often preferred.

Finally, for a variety of reasons, many patients discontinue GLP-1 RA use. In fact, nearly 30% of individuals discontinued semaglutide in one large trial, with real-world estimates for GLP-1 RA discontinuation in the range of 50% to 75% at 12 months.¹¹ Relatively little research (at least compared to weight loss) has focused on maintaining weight loss, regardless of the method. By incorporating soy foods into the diet during weight loss, there is a greater chance these foods will be used upon discontinuation. Given the overall nutrient content, health benefits, and the variety available, there are ample reasons to encourage patients using GLP-1 RAs to try soy foods.

REFERENCES

1. Linge J, Birkenfeld AL, Neeland IJ. Muscle mass and glucagon-like peptide-1 receptor agonists: Adaptive or maladaptive response to weight loss? Circulation 2024;150(16):1288-98 doi: 10.1161/CIRCULATIONAHA.124.067676 [published Online First: 2024/10/14 22:18].

2. Conte C, Hall KD, Klein S. Is weight loss-induced muscle mass loss clinically relevant? JAMA 2024;332(1):9-10 doi: 10.1001/jama.2024.6586 [published Online First: 2024/06/03].

3. Hughes GJ, Ryan DJ, Mukherjea R, Schasteen CS. Protein digestibility-corrected amino acid scores (PDCAAS) for soy protein isolates and concentrate: Criteria for evaluation. J Agric Food Chemistry 2011;59(23):12707-12 doi: 10.1021/jf203220v [published Online First: 2011/10/25].

4. Jenkins DJ, Mirrahimi A, Srichaikul K, et al. Soy protein reduces serum cholesterol by both intrinsic and food displacement mechanisms. J. Nutr. 2010;140(12):2302S-11S doi: jn.110.124958 [pii] 10.3945/jn.110.124958 [published Online First: 2010/10/15].

5. Blanco Mejia S, Messina M, Li SS, et al. A meta-analysis of 46 studies identified by the FDA demonstrates that soy protein decreases circulating LDL and total cholesterol concentrations in adults. J. Nutr. 2019;149(6):968-81 doi: 10.1093/jn/nxz020 [published Online First: 2019/04/23].

6. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N. Engl. J. Med. 2023;389(24):2221-32 doi: 10.1056/NEJMoa2307563 [published Online First: 2023/11/12].

7. Erlich MN, Ghidanac D, Blanco Mejia S, et al. A systematic review and meta-analysis of randomized trials of substituting soymilk for cow's milk and intermediate cardiometabolic outcomes: understanding the impact of dairy alternatives in the transition to plant-based diets on cardiometabolic health. BMC Med 2024;22(1):336 doi: 10.1186/s12916-024-03524-7 [published Online First: 2024/08/22].

8. Wadden TA, Chao AM, Moore M, et al. The role of lifestyle modification with second-generation anti-obesity medications: comparisons, questions, and clinical opportunities. Current obesity reports 2023;12(4):453-73 doi: 10.1007/s13679-023-00534-z [published Online First: 2023/12/02].

9. Weaver CM, Heaney RP, Connor L, Martin BR, Smith DL, Nielsen E. Bioavailability of calcium from tofu vs. milk in premenopausal women. J Food Sci 2002;68:3144-47.

10. Zhao Y, Martin BR, Weaver CM. Calcium bioavailability of calcium carbonate fortified soymilk is equivalent to cow's milk in young women. J. Nutr. 2005;135(10):2379-82.

11. Khan SS, Ndumele CE, Kazi DS. Discontinuation of glucagon-like peptide-1 receptor agonists. JAMA 2025;333(2):113-14 doi: 10.1001/jama.2024.22284 [published Online First: 2024/11/13].