Skip to main content

Effects of a low-protein nutritional formula with dietary counseling in older adults with chronic kidney disease stages 3–5: a randomized controlled trial



Although combining a low-protein diet (LPD) with oral nutritional supplements increases treatment adherence and nutritional status in patients with chronic kidney disease (CKD), the effect of this combination approach in older adults remains unclear. This study examined the impact of a 6% low-protein formula (6% LPF) with diet counseling in older adults with stage 3–5 CKD.


In this three-month randomized controlled study, 66 patients (eGFR < 60 mL/min/1.73 m2, non-dialysis, over 65 years of age) were randomly assigned to an intervention group (LPD plus a 6% LPF) or control group (LPD alone). The 6% LPF comprised 400 kcal, 6 g of protein, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and various micronutrients. All data were collected at baseline and after three months, including physical performance based on hand grip strength (HGS) and gait speed, nutritional status using Mini Nutritional Assessment-Short Form (MNA-SF) scores, body composition through bioelectrical impedance analysis, and dietary intake from 24-h dietary records.


This study incorporated 47 participants (median age, 73; median eGFR, 36 ml/min/1.73 m2; intervention group: 24; control group: 23). The intervention group exhibited significant differences in HGS and gait speed, and micronutrient analysis revealed significantly higher monounsaturated fatty acids (MUFA), EPA, DHA, calcium, iron, zinc, copper, thiamine, riboflavin, niacin, B6, B12, and folic acid intake than the control group. MNA-SF scores, macronutrient intake, and body composition did not differ significantly between the two groups.


Compared to LPD counseling alone, an LPD prescription with 6% LPF in older adults with CKD stages 3–5 helped relieve physical deterioration and increased micronutrient intake after three months.

Trial registration NCT05318014 (retrospectively registered on 08/04/2022).

Peer Review reports


Chronic kidney disease (CKD) is a prevalent clinical issue that is often observed in older adults [1, 2]. Older adults with CKD may experience muscle mass shrinkage, muscle strength deterioration, decreased physical performance, and protein-energy wasting [3], contributing to mobility issues and mortality, with inadequate nutrient intake as a prominent factor [4]. Therefore, nutritional management has become essential for older adults with CKD.

Recent nutritional guidelines have suggested that a low-protein diet (LPD) can be prescribed to slow kidney function progression, improving uremia and azotemia symptoms [5,6,7]. However, uremic anorexia or LPD food restriction often contributes to insufficient energy and protein intake, muscle and fat loss, and reduced body weight [8]. LPDs for patients over 65 years with CKD may lower albumin levels, body weight, and body mass index (BMI) [9], mainly due to this diet’s poor caloric intake [10]. Furthermore, an LPD can lead to insufficient micronutrient intake, such as vitamins and trace elements [11], thereby exacerbating diminished physical performance risks related to other comorbidities, including weakness, frailty, and muscle spasms [12].

An LPD for older adults with CKD should be prescribed based on the individual with a thorough patient nutritional status evaluation. When addressing renal failure progression, implementing an LPD as a nutritional education guideline is challenging and should only be individually prescribed to patients with CKD after considering the patient’s adherence, age, and nutritional status [13]. Recent literature discussed the combination of dietary prescriptions and oral nutritional supplements, which support adequate dietary intake to maintain or improve body weight, body composition, and physical performance in older malnourished adults [14, 15]. Past studies have positively affected adherence to an LPD and nutritional status in patients with CKD stage 3–5 by combining low-protein nutritional formulas with dietitian dietary counseling; however, few empirical studies have focused on older adults [16, 17]. Thus, this study compared the effects of a regular LPD alone or a 6% LPF combined with a regular LPD prescription on nutrition status, physical performance, and clinical parameter changes in older adults with CKD stages 3–5.


Study design and participants

This study was a single-center, two-armed, open-label, parallel, randomized controlled clinical trial. Participants were recruited from August 2019 to March 2020. The Institutional Review Board of Taichung Veterans General Hospital approved this study (IRB approval number: CF19237B). All participants provided their informed consent before participating in the study. Study participants were selected and recruited by the department’s physician and dietitian investigator. The inclusion criteria were as follows: nephrology clinic outpatients over the age of 65 years who were diagnosed with stage 3–5 CKD, a mean estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, and a non-dialysis status. The exclusion criteria were as follows: unstable conditions; leg injury; severe edema; allergies to foods such as milk, soy, or fish; use of heart rhythm devices or prosthetic limbs; relevant psychiatric disorders; and an inability to implement a 24-h dietary record. This trial was retrospectively registered at NCT05318014 on August 4, 2022.

Study treatments

Participants were allocated at a 1:1 ratio using a computer-generated random consecutive number list. Patients were divided into two groups: (1) the control group, patients received a regular LPD prescription; (2) the intervention group, patients received a regular LPD prescription with 6% LPF. All patients received an LPD prescription clinical guideline recommendation of protein intake (0.6–0.8 g/kg body weight/day) and energy requirement (30 kcal/body weight/day) [18, 19]. The LPD prescription was to assist patients in improving energy intake and implementing portion control of protein-containing foods through regular food sources. Table 1 lists the nutritional composition of 6% LPF, including a high-calorie liquid formula containing 400 kcal, 6 g of protein (6% of calories), and various nutrients (Fresubin® Renal, Germany). After face-to-face nutritional therapy during the first visit, patients were contacted by telephone to monitor their LPD prescription and adherence to 6% LPF after one and two months with the same registered dietitian during the study period. Compliance was calculated as the prescribed 6% LPF consumed after three months. Data were collected at baseline and at 3-month visits.

Table 1 6% low-protein formula nutritional compositions

Outcome measures

Nutrition status, physical activity, and body composition

The nutritional status assessment used the Mini Nutritional Assessment-Short Form (MNA-SF) [20]. Physical activity levels were measured using a Taiwanese version of the International Physical Activity Questionnaire-Short Form (IPAQ-SF) approved by the Taiwan Health Promotion Administration of the Ministry of Health and Welfare. The IPAQ-SF collected results regarding activity intensity of more than 10 min over the previous seven days and calculated the metabolic equivalent task (MET-min/week: 8 × vigorous + 4 × moderate + 3.3 × walking) by adding frequency, intensity, and duration [21, 22]. The following body composition data were collected and measured using bioelectrical impedance analysis (Tanita MC-780, Tanita Corporation of Akita Ltd., Japan): body weight (kg), BMI (kg/m2), body fat percentage (%), fat mass, fat-free mass, muscle mass, extracellular water, intracellular water, skeletal muscle index, resistance at 50 kHz, and phase angle.

Physical performance

Physical performance was measured by hand grip strength (HGS) and gait speed; HGS was measured with a TTM-YD hand dynamometer (Tsutsumi Industries, Tokyo, Japan) to identify muscle strength. Participants were placed in a sitting position with their elbow fixed at 90° and in the nondominant hand squeezed twice, with the mean results used for analysis. Gait speed was measured by physical movement via a 5-m walking test. Participants wore shoes and walked at their regular walking speed using a walking aid if necessary. The usual gait speed measured how many seconds the participant needed to walk 5 m and was recorded as m/s [23].

Dietary intake assessment

The 24-h dietary records using models or a food photography atlas were used to estimate portion sizes. When nutritional supplements were taken, intake frequency, dosage, and contents were recorded and incorporated into the total nutrient intake calculation. The dietitian coded and entered records obtained from an internet database created by the Food and Drug Administration regarding food and nutrition composition in Taiwan. We analyzed dietary intake, total energy intake, three macronutrient levels (carbohydrates, proteins, and lipids), fatty acid composition, saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids ([PUFA]; eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]), minerals (sodium, potassium, calcium, magnesium, phosphorus, iron, zinc, and copper), and vitamins (E, C, thiamine, riboflavin, niacin, B6, B12, and folic acid).

Clinical parameter measurements

Clinical parameters were collected through blood after fasting for at least 8 h, and blood urea nitrogen (BUN), creatinine, albumin, low-density lipoprotein (LDL), triglycerides, hemoglobin, and alanine aminotransferase (ALT) were recorded. The eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) study and the CKD-EPI equations [24, 25]. Laboratory analyses followed standard laboratory procedures at the Taichung Veterans General Hospital.

Statistical analysis

The total sample size involved 47 subjects based on a power of 90% using the Wilcoxon signed-rank test and a presumed moderate effect size of 0.5 at the \(\mathrm{\alpha }\) = 0.05 significance level. The sample size was calculated using G * Power version 3.1.3 (a program written by Franz Faul, Kiel University, Germany). Assuming an approximately 30% dropout rate, we considered enrolling 33 participants per group, resulting in 66 of the total participants [26, 27]. Descriptive statistics were calculated, and analysis methods were performed using the median and interquartile range (IQR) or numbers and percentages (%). Categorical variables were analyzed using the chi-square, Mann–Whitney U, and Fisher’s exact tests. Intragroup comparisons were accomplished using the Wilcoxon signed-rank test. For intergroup comparisons, data were analyzed with the Mann–Whitney U test. All data were collected, coded, verified for accuracy, and entered into a computer prior to statistical analysis with IBM® SPSS® version 22.0 (International Business Machines Corp., New York, NY, USA). Results at a P < 0.05 were considered statistically significant.



Participants (n = 95) were recruited, and 29 were excluded because they declined to participate or did not meet the inclusion criteria. Ultimately, this study included 66 participants who were randomized into two groups. After three months of follow-up, overall adherence at the study’s end revealed 47 participants the following (Fig. 1). The baseline characteristics of the two groups did not differ significantly and are presented in Table 2.

Fig. 1
figure 1

CONSORT flow diagram of participant recruitment

Table 2 Baseline data of the two older adult groups with CKD stages 3–5

Compliance with the 6% LPF

In the intervention group, the 6% LPF supplementation compliance at three months was 91.6%. A total of 33.3% of patients took 100% of the ONS, 20.8% took between 90 and 99% of the ONS, 37.5% took between 80 and 89.9% of the ONS, and 8.3% took between 70 and 79% of the ONS.

MNA-SF, IPAQ-SF, and body composition comparisons between groups

After a three-month follow-up, the scores on the MNA-SF and IPAQ-SF did not differ significantly within the two groups or between value changes. However, while body composition data indicated increased in weight, BMI, muscle mass, and lean mass, these changes were not significant in the intervention group at the three-month follow-up. Furthermore, the two groups had no significant differences in body composition at the three-month follow-up (Table 3).

Table 3 MNA-SF, physical activity, body composition, and physical performance outcomes

Physical performance effects

HGS (kg) decreased in the control group from baseline to three months, with a change of -1.2 kg (IQR, -2.6 to 0.1; P = 0.022). In contrast, the intervention group did not exhibit any significant differences. Furthermore, gait speed (m/s) slightly increased in the intervention group, with a change of 0.07 m/s (IQR, -0.02 to 0.22; P = 0.048) (Table 3). There was a significant difference in value changes for HGS (kg) and gait speed (m/s) when comparing the intervention group to the control group (P = 0.004 and P = 0.009, respectively) (Fig. 2).

Fig. 2
figure 2

The box plot displays the physical performance parameters from a three-month treatment follow-up. A Hand grip strength (kg). B Gait speed (m/s). Data are expressed as the median (interquartile range). Comparisons within groups from baseline to three months were performed using the Wilcoxon signed-rank test (†P < 0.05). Value change differences between intervention and control groups as determined by the Mann–Whitney U test (*P < 0.05, ** P < 0.01)

Results from 24-h diet records

Baseline calcium intake was higher in the control group than in the intervention group, without any other significant differences (data not shown). In terms of macronutrient intake, there was no significant difference between the two groups. Regarding fatty acid components, MUFA and EPA intake significantly increased in the intervention group, and the MUFA, EPA, and DHA intake changes heightened considerably between the two groups. For mineral intake, calcium, iron, zinc, and copper all significantly increased within the intervention group. Additionally, the intervention group’s change in intake increased notably more than that of the control group. For vitamin component intake, including thiamine, riboflavin, niacin, vitamin B6, vitamin B12, and folate, there were significant increases within the intervention group. Similarly, value changes in the intervention group showed a significant increase in vitamin component intake compared with the control group (Table 4).

Table 4 Macronutrients, Fatty acids, and micronutrients outcomes assessment with 24-h dietary records

Clinical parameter outcomes

Baseline clinical values did not differ significantly between groups. From baseline to three months, BUN induced a -2 mg/dl value change (IQR, -6 to -1; P = 0.03) in the intervention group, whereas no changes were observed in the control group (P = 0.80). There were no statistically significant changes in eGFR and other clinical parameters, and no significant differences were observed in the groups’ value shifts (Table 5).

Table 5 Clinical parameter outcomes from the two groups in older adults with stage 3–5 CKD


This study is the first to explore oral nutritional supplement effects in an older individual in stage 3–5 CKD at the 3-month follow-up period. We discovered that maintaining nutritional status consists of the MNA-SF, physical activity and body composition in both groups. A recent systematic review indicated that dialysis treatment involving a mix of various macronutrients for up to 12 months significantly increased lean body mass [28]. In a previous single-arm study, 35 patients with stage 3b-5 CKD adhering to a dietitian-guided LPD and a renal-specific formula noted considerable improvements in body weight and grip strength over six months [29]. In contrast with past studies, our findings showed that an LPD combined with a 6% LPF prompted a slight increase in body weight, muscle mass, and fat-free mass. Although the data were not significantly different between groups over three months, future long-term studies may be able to observe such differences.

In a previous study, an LPD of approximately 85% for patients with CKD stages 3–5 offered an insufficient daily calorie intake despite receiving standard routine diet counseling, while also associated with a slight decrease in gait speed [30]. These study data suggest that with an LPD prescription plus a 6% LPF, an increase in HGS and gait speed was observed compared to the LPD prescription alone. This result seems to imply that an LPD prescription plus a 6% LPF was a positive steady delay in physical function.

This study's results indicated that an LPD plus a 6% LPF provided no changes in energy and protein intake while increasing fatty acid and specific micronutrient intake during the 3-month follow-up period. Outcomes could be attributed to the two groups following the target calorie and protein intake under a dietitian’s guidance. The intervention group used oral nutritional supplements (6% LPF) to replace high-protein foods and achieve target energy intake and protein control. The control group used natural food during implementation. In a previous survey study, protein intake restrictions required energy supplements to avoid malnutrition and protein-energy wasting, potentially facilitating the use of protein-free products or other options as their primary energy source [31]. Furthermore, LPDs often lack variety, increasing the chances that a patient’s micronutrient intake will be lower [12]. This may be consistent with our finding, resulting in a decline in the intake of fatty acids and multivitamins estimated under the control of protein intake. However, maintaining a low-protein diet while consuming sufficient calories and nutrients may not be achieved through fatty acid or micronutrient supplementation alone.

Recent reports found that n-3 PUFA supplementation through a fish oil source enhanced muscle protein synthesis rates in older adults, improving muscle strength and boosting physical performance [32, 33]. Vitamin B and certain minerals are closely related to physical function [34, 35], and additional reports have suggested that administering multiple nutrients may be more effective than single-nutrient supplementation to prevent age-related muscle mass and strength attenuation [36,37,38]. However, it is unclear which types of nutrients affect muscle strength and gait speed in older adults with CKD stages 3–5. An LPD regimen with a 6% LPF prescription may be applied favorably in physical performance.

Regarding clinical parameters, this study also concluded that BUN was significantly reduced in the intervention group over three months. Previous randomized controlled trials have suggested that low-protein formula supplements could improve LPD adherence and kidney function outcomes [16, 17]. One case‒control observational study demonstrated that nutritional consulting was helpful for phosphorus and BUN clinical indications compared to no nutritional consulting [39]. Although kidney function results were inconsistent, a renal dietitian may have advised all participants. The results of these previous studies provide potential reasons why a 6% LPF does not significantly change renal function compared to a control group in older adults with CKD stages 3–5.

This study has several limitations. First, this study was conducted in a single center; therefore, the generalizability of the results may be poor. Second, concerning dietary intake, although previous studies of homebound older adults have proven reliable using a 24-h dietary record for energy intake, there may be a validity bias when describing information [40]. Third, the study design was open-label, and outcome assessments may have been biased in both groups. The results measuring physical activity (IPAQ-SF), which may influence bias, and no significant change between the two groups. Therefore, physical performance was chosen as the objective measure to mitigate outcome effects. Additionally, three months may be too short to identify the full impact of the outcome. Finally, all participants were adults over 65 and could not be extrapolated to other age groups, excluding other age group populations.


This study established that an LPD prescription with a 6% LPF can delay physical performance deterioration and increase micronutrient intake in three months compared to LPD education alone in older adults with CKD stages 3–5. Future studies should incorporate other age groups and a longer duration to validate these findings.

Availability of data and materials

The datasets analyzed during this study are available through the corresponding author upon reasonable request.



Alanine aminotransferase


Body mass index


Blood urea nitrogen


Chronic kidney disease


Docosahexaenoic acid


Estimated glomerular filtration rate


Eicosapentaenoic acid


Interquartile range


International Physical Activity Questionnaire-Short Form


Low-density lipoprotein


Low protein diet

6% LPF:

6% Low-protein formula


Hand grip strength


Mini Nutritional Assessment Short-Form


Monounsaturated fatty acids


Polyunsaturated fatty acids


Saturated fatty acids


  1. Tsai MH, Hsu CY, Lin MY, Yen MF, Chen HH, Chiu YH, et al. Incidence, Prevalence, and Duration of Chronic Kidney Disease in Taiwan: Results from a Community-Based Screening Program of 106,094 Individuals. Nephron. 2018;140:175–84.

    Article  PubMed  Google Scholar 

  2. Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl. 2022;12:7–11.

    Article  Google Scholar 

  3. Sabatino A, Cuppari L, Stenvinkel P, Lindholm B, Avesani CM. Sarcopenia in chronic kidney disease: what have we learned so far? J Nephrol. 2021;34:1347–72.

    Article  PubMed  Google Scholar 

  4. Hanna RM, Ghobry L, Wassef O, Rhee CM, Kalantar-Zadeh K. A practical approach to nutrition, protein-energy wasting, sarcopenia, and cachexia in patients with chronic kidney disease. Blood Purif. 2020;49:202–11.

    Article  CAS  PubMed  Google Scholar 

  5. Ikizler TA, Burrowes JD, Byham-Gray LD, Campbell KL, Carrero JJ, Chan W, et al. KDOQI Clinical practice guideline for nutrition in CKD: 2020 update. Am J Kidney Dis. 2020;76:S1–107.

    Article  CAS  PubMed  Google Scholar 

  6. Fiaccadori E, Sabatino A, Barazzoni R, Carrero JJ, Cupisti A, De Waele E, et al. ESPEN guideline on clinical nutrition in hospitalized patients with acute or chronic kidney disease. Clin Nutr. 2021;40:1644–68.

    Article  CAS  PubMed  Google Scholar 

  7. Cupisti A, Gallieni M, Avesani CM, D’Alessandro C, Carrero JJ, Piccoli GB. Medical nutritional therapy for patients with chronic kidney disease not on dialysis: the low protein diet as a medication. J Clin Med. 2020;9:3644.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kovesdy CP, Kopple JD, Kalantar-Zadeh K. Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: reconciling low protein intake with nutritional therapy. Am J Clin Nutr. 2013;97:1163–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Noce A, Vidiri MF, Marrone G, Moriconi E, Bocedi A, Capria A, et al. Is low-protein diet a possible risk factor of malnutrition in chronic kidney disease patients? Cell Death Discov. 2016;2:16026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Obi Y, Qader H, Kovesdy CP, Kalantar-Zadeh K. Latest consensus and update on protein-energy wasting in chronic kidney disease. Curr Opin Clin Nutr Metab Care. 2015;18:254–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. MacLaughlin HL, Friedman AN, Ikizler TA. Nutrition in kidney disease: core curriculum 2022. Am J Kidney Dis. 2022;79:437–49.

    Article  PubMed  Google Scholar 

  12. Jankowska M, Rutkowski B, Dębska-Ślizień A. Vitamins and microelement bioavailability in different stages of chronic kidney disease. Nutrients. 2017;9:282.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Piccoli GB, Cederholm T, Avesani CM, Bakker SJL, Bellizzi V, Cuerda C, et al. Nutritional status and the risk of malnutrition in older adults with chronic kidney disease - implications for low protein intake and nutritional care: A critical review endorsed by ERN-ERA and ESPEN. Clin Nutr. 2023;42:443–57.

    Article  CAS  PubMed  Google Scholar 

  14. Chew STH, Tan NC, Cheong M, Oliver J, Baggs G, Choe Y, et al. Impact of specialized oral nutritional supplement on clinical, nutritional, and functional outcomes: A randomized, placebo-controlled trial in community-dwelling older adults at risk of malnutrition. Clin Nutr. 2021;40:1879–92.

    Article  CAS  PubMed  Google Scholar 

  15. Volkert D, Beck AM, Cederholm T, Cruz-Jentoft A, Hooper L, Kiesswetter E, et al. ESPEN practical guideline: clinical nutrition and hydration in geriatrics. Clin Nutr. 2022;41:958–89.

    Article  CAS  PubMed  Google Scholar 

  16. Wu HL, Sung JM, Kao MD, Wang MC, Tseng CC, Chen ST. Nonprotein calorie supplement improves adherence to low-protein diet and exerts beneficial responses on renal function in chronic kidney disease. J Ren Nutr. 2013;23:271–6.

    Article  CAS  PubMed  Google Scholar 

  17. Kanazawa Y, Morita S, Sonoki H, Nakao T. Effects of a novel nutritional formula specially developed for chronic kidney disease patients on protein-restricted diets: a randomized controlled trial. Ren Replace Ther. 2016;2:18.

    Article  Google Scholar 

  18. Kalantar-Zadeh K, Fouque D. Nutritional Management of Chronic Kidney Disease. N Engl J Med. 2017;377:1765–76.

    Article  CAS  PubMed  Google Scholar 

  19. Kopple JD. National kidney foundation K/DOQI clinical practice guidelines for nutrition in chronic renal failure. Am J Kidney Dis. 2001;37:S66–70.

    Article  CAS  PubMed  Google Scholar 

  20. Rubenstein LZ, Harker JO, Salvà A, Guigoz Y, Vellas B. Screening for undernutrition in geriatric practice: developing the short-form mini-nutritional assessment (MNA-SF). J Gerontol A Biol Sci Med Sci. 2001;56:M366–72.

    Article  CAS  PubMed  Google Scholar 

  21. Liou YM, Jwo CJ, Yao KG, Chiang LC, Huang LH. Selection of appropriate Chinese terms to represent intensity and types of physical activity terms for use in the Taiwan version of IPAQ. J Nurs Res. 2008;16:252–63.

    Article  PubMed  Google Scholar 

  22. Lee PH, Macfarlane DJ, Lam TH, Stewart SM. Validity of the international physical activity questionnaire short form (IPAQ-SF): a systematic review. Int J Behav Nutr Phys Act. 2011;8:115.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Wilson CM, Kostsuca SR, Boura JA. Utilization of a 5-Meter Walk Test in Evaluating Self-selected Gait Speed during Preoperative Screening of Patients Scheduled for Cardiac Surgery. Cardiopulm Phys Ther J. 2013;24:36–43.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, et al. Expressing the modification of diet in renal disease study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem. 2007;53:766–72.

    Article  CAS  PubMed  Google Scholar 

  25. Inker LA, Eneanya ND, Coresh J, Tighiouart H, Wang D, Sang Y, et al. New creatinine- and cystatin C-Based equations to estimate GFR without race. N Engl J Med. 2021;385:1737–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175–91.

    Article  PubMed  Google Scholar 

  27. Cohen J. Statistical power analysis for the behavioral sciences. London: Taylor & Francis; 2013.

    Book  Google Scholar 

  28. Lu Y, Wang YJ, Lu Q. The effect of oral nutritional supplement on muscle fitness of patients undergoing dialysis: A systematic review and meta-analysis. J Adv Nurs. 2021;77:1716–30.

    Article  PubMed  Google Scholar 

  29. Kelly OJ, Huang MC, Liao HY, Lin CC, Tung TY, Cheng RW, et al. A Low-Protein Diet with a Renal-Specific Oral Nutrition Supplement Helps Maintain Nutritional Status in Patients with Advanced Chronic Kidney Disease. J Pers Med. 2021;11:1360.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Hsu HJ, Yen CH, Wu IW, Liu MH, Cheng HY, Lin YT, et al. The association between low protein diet and body composition, muscle function, inflammation, and amino acid-based metabolic profile in chronic kidney disease stage 3–5 patients. Clin Nutr ESPEN. 2021;46:405–15.

    Article  PubMed  Google Scholar 

  31. D’Alessandro C, Rossi A, Innocenti M, Ricchiuti G, Bozzoli L, Sbragia G, et al. Dietary protein restriction for renal patients: don’t forget protein-free foods. J Ren Nutr. 2013;23:367–71.

  32. Huang YH, Chiu WC, Hsu YP, Lo YL, Wang YH. Effects of Omega-3 Fatty Acids on Muscle Mass, Muscle Strength and Muscle Performance among the Elderly: A Meta-Analysis. Nutrients. 2020;12:3739.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Xu D, Lu Y, Yang X, Pan D, Wang Y, Yin S, et al. Effects of fish oil-derived n-3 polyunsaturated fatty acid on body composition, muscle strength and physical performance in older people: a secondary analysis of a randomised, double-blind, placebo-controlled trial. Age Ageing. 2022;51:afac274.

    Article  PubMed  Google Scholar 

  34. O’Connell ML, Coppinger T, McCarthy AL. The role of nutrition and physical activity in frailty: A review. Clin Nutr ESPEN. 2020;35:1–11.

  35. Bonnefoy M, Berrut G, Lesourd B, Ferry M, Gilbert T, Guérin O, et al. Frailty and nutrition: searching for evidence. J Nutr Health Aging. 2015;19:250–7.

    Article  CAS  PubMed  Google Scholar 

  36. Ganapathy A, Nieves JW. Nutrition and Sarcopenia-What Do We Know? Nutrients. 2020;12:1755.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Granic A, Dismore L, Hurst C, Robinson SM, Sayer AA. Myoprotective whole foods, muscle health and sarcopenia: a systematic review of observational and intervention studies in older adults. Nutrients. 2020;12:2257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Yokoyama Y, Kitamura A, Seino S, Kim H, Obuchi S, Kawai H, et al. Association of nutrient-derived dietary patterns with sarcopenia and its components in community-dwelling older Japanese: a cross-sectional study. Nutr J. 2021;20:7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Cupisti A, D’Alessandro C, Di Iorio B, Bottai A, Zullo C, Giannese D, et al. Nutritional support in the tertiary care of patients affected by chronic renal insufficiency: report of a step-wise, personalized, pragmatic approach. BMC Nephrol. 2016;17:124.

  40. Sun Y, Roth DL, Ritchie CS, Burgio KL, Locher JL. Reliability and predictive validity of energy intake measures from the 24-hour dietary recalls of homebound older adults. J Am Diet Assoc. 2010;110:773–8.

    Article  PubMed  PubMed Central  Google Scholar 

Download references


We thank Fresenius Kabi Taiwan Ltd. for freely providing the 6% LPF (brand name: Fresubin® Renal; manufacturer: Fresenius Kabi Deutschland GmbH). The funders had no role in study design, data collection and analysis, publication decisions, or manuscript preparation.


The study was supported by a grant from Taichung Veterans General Hospital (grant no. TCVGH-1096201A and TCVGH-1103603D).

Author information

Authors and Affiliations



WCY, HMH, and CHC: designed the research, coordinated the study, and interpreted the data. WCY and LCL: performed data acquisition. JPC: data curation and statistical analysis. WCY: wrote the original manuscript. HMH and CHC: reviewed and extensively revised the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Cheng-Hsu Chen.

Ethics declarations

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki guidelines and approved by the Ethical Committee for Institutional Review Board of Taichung Veterans General Hospital (approval number CF19237B, registered on August 20, 2019). Informed consent was obtained from all subjects involved in this study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, WC., Hsieh, HM., Chen, JP. et al. Effects of a low-protein nutritional formula with dietary counseling in older adults with chronic kidney disease stages 3–5: a randomized controlled trial. BMC Nephrol 24, 372 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: