Impact of a Low-Carbohydrate Diet Versus a Regular Diet on Vitamin B Levels in Overweight and Obese Patients with Type 2 Diabetes Mellitus in Saudi Arabia

Introduction

The increasing prevalence of Type 2 Diabetes Mellitus has become a major global public health concern, particularly in regions such as the Middle East and Saudi Arabia, where lifestyle-related factors have contributed to rising rates of obesity and diabetes.¹ In Saudi Arabia, the prevalence of diabetes among adults has reached 23.7%, placing the country among those with the highest diabetes rates worldwide.^2,3 T2DM is associated with multiple comorbidities, including cardiovascular disease, retinopathy, nephropathy, and neuropathy, all of which contribute to a higher burden on healthcare systems.⁴ The burden of diabetes continues to grow among the Saudi population. As more individuals are newly diagnosed, the overall risk for a range of serious complications increases, including limb amputations, nerve damage, kidney failure, vision loss, high blood pressure, stroke, cardiovascular disease, dental issues, and repeated amputations.⁵ Waghet al, Projected in their recent publication that global annual deaths attributable to diabetes will reach approximately 1.63 million by 2030 (95% PI: 1.48–1.91 million), reflecting an increase of about 10% compared with mortality levels reported in 2019.⁶

The 2024 nutrition guidelines from the American Diabetes Association (ADA) emphasize a flexible, patient-centered approach to dietary management for individuals with diabetes. The main objective is to promote healthy dietary habits that emphasize the intake of diverse nutrient-dense foods in appropriate portion sizes. This strategy supports overall well-being by helping individuals attain and sustain healthy body weight, achieve individualized goals for glycemic control, blood pressure, and lipid levels, and potentially prevent or postpone diabetes-related complications.⁷

The low-carbohydrate diet (LCD) has gained attention as a potential intervention for managing T2DM, particularly among overweight and obese individuals^. This nutritional strategy emphasizes reducing carbohydrate consumption while increasing the intake of proteins and healthy fats, which may contribute to better glycemic control, support weight reduction, and improve insulin sensitivity.⁸ Evidence suggests that LCDs can lead to significant improvements in HbA1c, a key marker of glycemic control, as well as reductions in body weight, making them a popular alternative to traditional dietary recommendations.^8,9-11

In recently published systematic review reports limited research has specifically evaluated the risk of micronutrient deficiencies associated with long-term adherence to these diets in diabetic populations. Most existing studies primarily focus on metabolic outcomes such as HbA1c, weight loss, and lipid profiles, while the nutritional adequacy and micronutrient status of individuals following LCDs remain insufficiently investigated.^12,13 Metformin, the cornerstone of T2DM management, has been associated with vitamin B12 deficiency due to its effect on vitamin absorption in the gut.^14-18 This risk may be compounded in patients on restrictive diets, such as LCDs, which may limit the intake of certain nutrient-rich foods.

In Saudi Arabia, there is a scarcity of research exploring the relationship between dietary patterns, T2DM management, and micronutrient status, including vitamin B12 levels. Understanding the impact of different dietary approaches, such as an LCD compared to a regular diet, on vitamin B12 deficiency in this population is essential for developing comprehensive management strategies that address both macronutrient and micronutrient needs. This study aims to evaluate the effect of a low-carbohydrate diet versus a regular diet on vitamin B12 deficiency among overweight and obese individuals with T2DM in Saudi Arabia. 

Materials and Methods

We conducted a prospective cohort study at King Abdulaziz Medical City in Jeddah. A prospective cohort study was conducted in King Abdulaziz Medical City Jeddah.  In-person interviews were carried out using a structured checklist to gather information on demographic data, patient conditions, medications, vitamins B complex, multivitamins, diet, glycated hemoglobin levels, and vitamin B12 levels.  B-complex supplements were defined as preparations containing multiple B vitamins (B1, B2, B3, B5, B6, B7, B9, and B12) without additional vitamins or minerals.¹⁹ Multivitamins were defined as supplements containing a broad spectrum of vitamins (A, C, D, E, K, and B-complex) and minerals (e.g., calcium, magnesium, zinc).²⁰ The composition of each supplement was recorded based on manufacturer labeling where available.

The study’s inclusion criteria required participants to be Type II diabetic patients aged 30 years and above, with a Body Mass Index (BMI) greater than 25 kg/m², who had been taking oral antidiabetic medications, including metformin for over three months and were receiving care at a primary health care center in Jeddah. Patients were excluded if they have Diabetes Mellitus Type I, as well as those with a history of kidney insufficiency, liver disorders, or unstable cardiovascular diseases. Participants were divided into two groups: the intervention group (n=14), who followed a low-carbohydrate diet, and the control group (n=27), who followed a regular diet.

In this study, a consecutive sampling method was employed, whereby all accessible participants meeting the predefined inclusion criteria in widow period of 6 months were recruited. Eligible patients were informed about the study, and their written informed consents were obtained. The study protocol and informed consent form were reviewed and approved by the Institutional Review Board (IRB)/Research Ethics Committee of King Abdullah International Medical Research Center under protocol number (SP23J/001/01) on 12/02/2023. The study was conducted in compliance with the ethical standards of the institutional and national research committees and in accordance with the principles of the Declaration of Helsinki.²¹

Low carbohydrates diet (LCD) has been defined as consuming less than 130 g/day of carbohydrates or <26% carbohydrates.²² Participants received a brochure detailing a low-carbohydrate diet plan that restricts carbohydrates while focusing on high-protein and high-fat foods. Carbohydrate intake was initially restricted to 20 g/day to induce nutritional ketosis and optimize glycemic control.²³ Following established LCD protocols, carbohydrate allowance gradually increased by 5 g/week once weight loss plateaued, in order to improve long-term adherence, maintain metabolic benefits, and reduce the risk of micronutrient deficiency or hypoglycemia. There was no limit on the consumption of meat, poultry, fish, eggs, fats, and oils. Participants were educated individually or in small groups about specific food types and portions to consume or avoid.

Standardized equipment was utilized to measure body weight in kilograms and height in meters, and body mass index (BMI) was determined by dividing weight (kg) by the square of height (m²). Blood specimens were obtained between 7:00 and 10:00 a.m. following an overnight fast of approximately 10 hours at the start of the study and again after 12 weeks for both groups. Venipuncture was performed in the phlebotomy unit of the Department of Pathology and Laboratory Medicine. Before blood collection, anthropometric measurements, including blood pressure, height, and weight, were obtained. Approximately 10 mL of venous blood was collected into plain and EDTA-containing tubes for subsequent laboratory investigations.

HbA1c was measured using a Tosoh G8 automated analyzer (Tosoh Corporation, Tokyo, Japan) based on high-performance liquid chromatography (HPLC) with cation-exchange separation, which differentiates hemoglobin into six subfractions, including the A1C fraction corresponding to glycated hemoglobin.²⁴

Serum vitamin B12 concentrations were measured using the ARCHITECT B12 assay (Abbott Laboratories, Abbott Park, IL, USA), an automated chemiluminescent microparticle immunoassay (CMIA) performed according to the manufacturer’s protocol.²⁵ All assays were performed within one hour of sample collection to ensure accuracy and reliability.

Statistical analysis

Data processing and statistical analyses were performed using SPSS (IBM Corp., Armonk, NY, USA). Categorical variables were summarized as frequencies and percentages, with group comparisons assessed using the Chi-square test or Fisher’s exact test when appropriate. Continuous variables were expressed as mean ± standard deviation, and comparisons between groups were analyzed using the Student’s t-test. A P-value < 0.05 was considered statistically significant. 

Results

A total of 41 patients were enrolled in the study, with ages ranging from 30 to 82 years (mean age: 49±9.2 years). When comparing the two dietary groups, there were no significant differences in age, with the mean age being 49.37±7.39 for the low-carbohydrate diet group and 48.36±12.4 for the regular diet group, (P-value = 0.744).

Gender distribution was similar between groups, with males accounting for 57.1% in the low-carbohydrate diet group and 51.9% in the regular diet group (P = 0.747). Females were accounting for 42.9% and 48.1% in the Low- carbohydrate diet group and the regular diet group, respectively. Most participants (78%) were nonsmokers. The proportion of smokers was comparable in both groups, with 21.4% in the low-carbohydrate diet group and 22.2% in the regular diet group.

The duration of diabetes varied among participants, with 29 patients having diabetes for less than 10 years and 12 patients for 10 years or more. No significant difference was found in diabetes duration between groups, as 70.4% in both the low-carbohydrate diet and regular diet groups had diabetes for less than 10 years (P-value = 0.944).

Regarding metformin use, 65.9% of patients were on a dose higher than 1000 mg, while 34.1% were taking 1000 mg or less. There was a trend toward higher metformin doses in the low-carbohydrate diet group, with 85.7% of these patients taking more than 1000 mg compared to 55.6% in the regular diet group (P-value = 0.053). The median duration of metformin use was 5 years, with an interquartile range (IQR) of 9 years, and there was no significant difference in duration between the two groups (P-value = 0.659). The use of B-complex vitamins was significantly different between groups, with only 7.1% of the low-carbohydrate diet group taking B-complex vitamins compared to 40.7% in the regular diet group (P-value = 0.025). Lastly, no patients in the low-carbohydrate diet group were taking multivitamins, while 11.1% of the regular diet group reported using multivitamins (P-value = 0.539). All data are summarized in Table 1.

Table 1: Characteristics and demographic data of diabetic patients on Low Carbohydrate diet versus regular diet.

SD: Standard deviation, no: number, DM: Diabetes mellites, IQR: Interquartile range.

^a Student T-test.

^b Chi-square test.

^c Mann-Whitney U test.

^d Fischer exacts test.

^* Statistically significant as per P-value < 0.05.

Vitamin B levels and HbA1c did not show significant changes over time within or between groups. Median Vitamin B levels slightly decreased after three months in both groups, with no statistically significant differences, (P-value= 0.221) for the low-carbohydrate diet group and (P-value= 0.400) for the regular diet group. Similarly, median HbA1c levels showed a downward trend in the low-carbohydrate diet group, from 7.15 to 6.6, but this change was not statistically significant (P-value= 0.109). In the regular diet group, HbA1c levels were stable and didn’t change significantly, (P-value= 0.264). All data are summarized in Table 2.

Table 2: Vitamin B level in diabetic patients following Low Carbohydrate diet versus regular diet.

IQR: Interquartile range, HbA1C: Glycated hemoglobin.

^e Wilcoxon Signed Ranks Test.

Table 3 showed Categories of Vitamin B level in diabetic patients following Low Carbohydrate diet versus regular diet. At the beginning of the study, vitamin B levels varied between the two dietary groups. Among participants following a low-carbohydrate diet, 12 patients had borderline vitamin B levels, while 2 patients had normal levels and no one was deficient of Vitamin B. In the regular diet group, 22 patients had borderline levels, 3 patients were in the normal range and 2 patients had a deficiency of vitamin B. The differences in vitamin B distribution between the groups at the start were not statistically significant, (P-value= 0.567).

The analysis of the association between vitamin B12 deficiency stages and the duration of diabetes (categorized as more than 10 years or 10 years or less) revealed no statistically significant relationship. The Pearson Chi-Square test yielded a P-value of 0.551, indicating that the distribution of vitamin B12 deficiency stages did not significantly differ based on diabetes duration. There was no statistically significant association between neither the daily dose of metformin nor the duration on metformin therapy, and the stage of vitamin B12 deficiency, (P-value of 0.469 & 0.499), respectively.

After three months, the low-carbohydrate diet group maintained similar vitamin B levels, with 12 patients remaining in the borderline range and 2 patients in the normal range. In the regular diet group, there was a slight improvement, with 21 patients having borderline levels and 6 patients achieving normal levels. No deficiencies were observed in either group at the three-month mark. The differences in vitamin B distribution after three months were still not statistically significant, (P-value= 0.543), indicating that neither diet led to substantial changes in vitamin B levels over the study period.

Table 3: Categories of Vitamin B level in diabetic patients following Low Carbohydrate diet versus regular diet.

no: number, ^b Chi-square test.

Discussion

The current study sought to evaluate and compare the impact of a low-carbohydrate diet (LCD) versus a standard diet on vitamin B12 levels and HbA1c among overweight and obese patients with Type 2 Diabetes Mellitus (T2DM) in Saudi Arabia. The results add to the expanding evidence on dietary approaches in diabetes management, emphasizing both the potential benefits and limitations of LCD use in a population with a high prevalence of diabetes.

No statistically significant differences were observed between the two dietary groups regarding age, sex distribution, smoking status, duration of diabetes, or metformin use, indicating that baseline characteristics were well balanced. A higher metformin dose was noted in the low-carbohydrate diet group; however, this difference did not achieve statistical significance (P = 0.053).

The gradual increase in carbohydrate intake after initial restriction was implemented to improve dietary sustainability, a common challenge in LCD interventions. Although this approach may have attenuated further weight loss in some individuals, it helped maintain adherence over the study period. The moderate weight reduction observed in the LCD group may have contributed to improvements in metabolic parameters, although the effect on vitamin B12 levels appeared minimal.

The comparison of vitamin B12 levels at baseline revealed that most participants in both groups had borderline levels, with no statistically significant difference between the groups (P = 0.567). Overall, 2 patients (4.5%) were vitamin B12 deficient, while 34 (77.3%) were classified as borderline. These findings are consistent with previous studies reporting similar patterns of vitamin B12 status across patient populations. In Type 2 Diabetes Mellitus, a considerable proportion of patients have been reported to exhibit suboptimal vitamin B12 levels (56%), with a smaller fraction showing true deficiency (10%)⁶. In contrast, another recent study reported a markedly higher prevalence of vitamin B12 deficiency (65.7%) among patients receiving metformin therapy.²⁷

Multiple risk factors have been associated with metformin-induced effects on vitamin B12 levels in patients with diabetes, particularly the dosage and duration of therapy. Long-term use of metformin has been shown to increase the risk of developing vitamin B12 deficiency.²⁸ It was reported in one study that 65.6% of metformin users exhibited low vitamin B12 levels, classified as either deficiency or insufficiency.²⁶ Various other studies have also highlighted that there is significant association between low serum B12 levels and metformin use.^29, Furthermore, vitamin B12 deficiency has been reported in as many as 93% of diabetic patients receiving metformin therapy.³¹ Studies have reported that deficiency of vitamin B12 is due to its malabsorption among T2DM patients treated with metformin.³² Several hypotheses have been proposed to explain how metformin has been shown to impair vitamin B12 absorption through multiple proposed mechanisms. metformin interferes with vitamin B12 absorption. These include disruption of the enterohepatic recycling of B12, enhanced storage of the vitamin in the liver, reduced production of intrinsic factor, and slower intestinal movement leading to bacterial overgrowth.^15,33 Moreover, it’s known that vitamins B are water soluble thus any excess vitamin B are washed out through urination and the body can’t easily store them for a long time.³⁴

Vitamin B12 deficiency associated with metformin use may result in hematologic changes such as anemia. Metformin-induced vitamin B12 deficiency can also lead to anemia. A lack of vitamin B12 disrupts the normal development of red blood cells, causing them to mature abnormally and take on irregular shapes, which results in megaloblastic anemia.³⁵ Additionally, the relationship between vitamin B12 deficiency and peripheral neuropathy in diabetic patients has been extensively studied. There was a link found between vitamin B12 deficiency and the occurrence of peripheral neuropathy in individuals with type 2 diabetes  with evidence suggesting that prolonged exposure between 12–15 years may be required for this to occur, moreover cumulative doses of metformin were correlated strongly with the differences seen.^31,36-39 In one prospective study on patients with diabetes suffering from peripheral neuropathy and been treated with metformin, there were significant lower vitamin B12 levels along with clear clinical and electrophysiological evidence of more severe peripheral neuropathy with elevated levels of methylmalonic acid and homocysteine levels.⁴⁰ Such findings underscore the importance of monitoring and potentially addressing vitamin B12 levels in this population to prevent associated complications.^41,42

After three months, a slight improvement in vitamin B status was observed in the regular diet group, with 22.2% of participants achieving normal levels compared to 14.3% in the LCD group. However, this change was not statistically significant (P-value = 0.543), indicating that neither diet produced substantial changes in vitamin B levels over the study period. The potential relationship between carbohydrate intake and vitamin B-complex status may be explained by both dietary and metabolic factors. Carbohydrate-rich foods such as whole grains, fortified cereals, and certain legumes are important sources of several B vitamins, including thiamine (B1), niacin (B3), and folate (B9). ^43,44 Restricting these foods, as in a low-carbohydrate diet, could reduce the overall intake of these micronutrients unless replaced by other nutrient-rich sources. Vitamin B12, although primarily derived from animal products, may also be indirectly affected if the dietary pattern limits fortified plant-based foods that contribute to total intake.^45,46

Furthermore, carbohydrate restriction can influence gut microbiota composition, which in turn may impact the synthesis and absorption of some B vitamins.^47,48 In individuals with type 2 diabetes, the situation is further complicated by metformin therapy, which is a well-recognized cause of reduced vitamin B12 absorption and may outweigh the dietary effects. Therefore, any association between carbohydrate ingestion and vitamin B-complex status in our study population should be interpreted within this multifactorial context, emphasizing the importance of dietary planning to ensure adequate micronutrient intake. This finding is also consistent with a previous study suggesting that LCD may be accompanied by more nutritional deficiencies particularly in the absence of supplementation.⁴⁹ These findings also align with a systematic review that identified insufficient intakes of magnesium, calcium, iron, iodine, thiamine, and folate among healthy adults adhering to a carbohydrate-restricted diet.⁵⁰ The findings of this study and all previous studies indicate that certain high-carbohydrate foods can be valuable sources of vitamins and minerals, either through naturally occurring nutrients or through fortification.

Notably, there was a significant difference in the use of B-complex vitamins between the two groups, with a greater proportion of participants in the regular diet group reporting supplementation compared to the low-carbohydrate diet group (40.7% vs. 7.1%, P = 0.025). This discrepancy could potentially influence the observed vitamin B levels, as supplementation may contribute to maintaining or improving vitamin B status, independent of dietary changes. The low uptake of vitamin B supplements in the LCD group may suggest the need for dietary counseling to address potential deficiencies associated with both carbohydrate-restricted diets and metformin use.

Similarly, the analysis of HbA1c levels did not show significant differences between the groups over time. The LCD group exhibited a non-significant downward trend in median HbA1c levels, decreasing from 7.15 to 6.6 (P-value = 0.109), while the regular diet group showed stable HbA1c levels (P-value = 0.264). These results indicate that although the low-carbohydrate diet (LCD) might have an effect on glycemic control more than that of the regular diet, the impact was not statistically significant in this study population. In contrast, another study reported a substantial drop in average HbA1c levels, from a baseline of 10.9 ± 1.6% to 7.8 ± 1.5% after 3 months, and a more gradual decrease to 7.4 ± 1.4% at 6 months, with these changes being statistically significant (P < 0.001).⁵¹ It is possible that a longer follow-up period or a larger sample size may be necessary to detect more pronounced differences in glycemic outcomes.

Although previous studies have reported that low-carbohydrate diets (LCDs) can lead to significant reductions in HbA1c, our study did not demonstrate this effect. Several factors may explain this discrepancy. First, the intervention period in our study was limited to three months, which may be insufficient to observe a measurable impact on HbA1c, especially given that this biomarker reflects average glycemic control over approximately the same duration. Second, baseline HbA1c levels in many participants were already close to target, reducing the potential for further improvement. Third, variations in individual adherence to the carbohydrate restrictions could have diluted the overall effect, and some participants may have consumed more carbohydrates than prescribed. In addition, any changes in antidiabetic medications during the study period could have confounded the dietary effect. Finally, the relatively small sample size may have limited our statistical power to detect subtle changes. These factors should be considered when interpreting the absence of a significant HbA1c reduction in the present study. It is possible that a longer follow-up period or a larger sample size may be necessary to detect more pronounced differences in glycemic outcomes.

Clinically, the data indicates that both diet groups experienced relatively stable Vitamin B levels over the study period, with a slight decrease in the low carbohydrate group (from 298.5 to 293) and a peripheral increase in the regular diet group (from 265 to 273). This suggests that neither dietary intervention significantly impacted Vitamin B levels in a clinically meaningful way. In the HbA1C, a low carbohydrate diet group demonstrated a clinically noticeable reduction from 7.15% to 6.6%, indicating an improvement in glycemic control, whereas the regular diet group showed a slight increase from 7.1% to 7.4%. This reduction in HbA1C in the low carbohydrate group may be clinically significant, as even a modest decrease in HbA1C is associated with a reduction in the risk of diabetes-related complications. Thus, while the statistical significance may not be strong, the clinical implications suggest that a low carbohydrate diet could be beneficial in managing HbA1C levels in diabetic patients.

Overall, the study did not demonstrate significant differences in the primary outcomes of vitamin B levels and HbA1c between the low-carbohydrate and regular diet groups. Further research with larger sample sizes, longer follow-up periods, and the inclusion of dietary supplement intake monitoring is warranted to better understand the potential benefits and limitations of different dietary approaches in the management of T2DM.

Study Limitation

While this study provides valuable insights, certain considerations should be kept in mind when interpreting the findings. Conducted at a single center with a modest sample size, the study’s generalizability to the broader diabetic population may be limited. A multi-center approach with a larger, more diverse sample could yield results that are more widely applicable. The three-month study duration may have been too brief to capture significant changes in vitamin B levels or glycemic control. Future research with longer follow-up periods could offer a clearer view of the long-term effects of dietary interventions. Finally, the use of markers like homocysteine and methylmalonic acid, may lead to better findings thus this study recommends future studies that include these elements for a thorough understanding of dietary impacts on vitamin B and blood sugar levels in individuals with Type 2 Diabetes Mellitus.

Conclusion

The findings from this study suggest that a low carbohydrate diet (LCD) does not significantly affect vitamin B levels or HbA1c when compared to a regular diet over a 12-week period in overweight and obese individuals with Type 2 Diabetes Mellitus (T2DM) in Saudi Arabia. Despite the popularity of LCDs in diabetes management, our results indicate that such diets may not pose an immediate risk of vitamin B deficiency in this patient population. However, given the borderline vitamin B levels observed across both groups, there may be an underlying risk that warrants further investigation. Larger, longer-term studies are recommended to better understand the potential effects of LCDs on micronutrient status and to determine if these diets can offer sustained benefits in glycemic control without compromising nutritional health.

Acknowledgement

The authors gratefully acknowledge King Abdullah International Medical Research Center (KAIMRC) for their support and for enabling the conduct of this research.

Funding Sources

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Conflicts of Interest

The author(s) do not have any conflict of interest.

Data Availability Statement

All data generated or analyzed during this study are included in this published article.

Ethics Statement

The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of King Abdullah International Medical Research Center IRP (SP23J/001/01) on [12/FEB/2023].

Informed Consent Statement

Informed consent was obtained from all individuals participants included in the study. The study was conducted in accordance with the Declaration of Helsinki, and approved by the King Abdullah International Medical Research Center (SP23J/001/01) on [12/FEB/2023].

Clinical Trial Registration

This research does not involve any clinical trials.

Permission to Reproduce Material from Other Sources

Not Applicable

Author Contributions

• Noura Fahad Aljahdali: Conceptualization, Data Collection,Methodology, Writing – Original Draft
• Magdi Osman: Conceptualization, supervision
• Nawal Abdullah Al-bader: visualization, writing – Review
• Khulood Abdullah Alsiary: Data Collection, writing – Review
• Lujain Ahmed Bahubaish: Data Collection

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Abbreviations

T2DM – Type 2 Diabetes Mellitus

LCD – Low-carbohydrate Diet

HbA1c – Glycated Hemoglobin

VB12 – Vitamin B12

BMI – Body Mass Index