Introduction

The B vitamins are essential water-soluble nutrients that include vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B7 (biotin), vitamin B9 (folate) and vitamin B12 (cobalamin). These vitamins play important roles in energy production, nutrient metabolism, hematopoiesis, and gene expression.¹ They also have benefits for the nervous system and gut microbiota regulation, and their deficiencies have been associated with a variety of neurodegenerative disorders and dysbiosis.²  Inadequacy in some of the status of B vitamins could have functional consequences on the other types of vitamin B complex, especially in one-carbon metabolism such as folate, vitamin B12, vitamin B6, and riboflavin, due to the interactions between B vitamins.

B vitamins complex status can be assessed by measuring the concentrations of these vitamins (or their metabolites) biochemically in the plasma/serum, erythrocytes, or urine.¹ In addition, the adequacy of dietary intakes can be determined by comparing the intake to the Dietary Reference Intakes (DRI).  The risk of B vitamins deficiency can lead to several diseases such as anemia, beriberi, and pellagra.  Individuals with B vitamins deficiency may experience fatigue, numbness or tingling, and weakened muscles³  Based on our current knowledge, no national studies have assessed the dietary intake of B vitamins in Saudi Arabia.Despite the low prevalence of veganism in Saudi Arabia (<8%),^4,5 several reports have indicated 10% of megaloblastic anemia ⁶ and about 25% of riboflavin deficiency.^7,8  This maybe due to the low consumption of fruit and vegetables, as less than 3% of Saudis met the recommendations for daily consumption of fruits and vegetable based on national estimates. ⁹

In Saudi Arabia, there are mandatory and voluntary fortification/enrichment policies of food items with some nutrients including folic acid, niacin, riboflavin, and thiamin.  Food fortification/ enrichment are required to be added to the wheat flour at the following amounts: 1.75, 52.91, 3.96, and 6.38 parts per million, respectively.¹⁰  Since 2000, Saudi Arabia has mandated folic acid fortification of wheat and enriched treated flour (150µg/100g) as an initiative to prevent neural tube defects (NTDs).¹¹  These policies can significantly contribute to the populations’ dietary intakes and improve biochemical status. It has been reported that incidence rate for NTDs has significantly decreased post folic acid fortification from 1.46 to 0.81 per 1000 live births.^12-14  Another study by Safdar et al. in 2007 found an apparent decline in the incidence of NTDs in newborns after folic acid flour fortification.¹²

Several studies examined individual B vitamin status in Saudi population, but there is a lack of reviews putting together these findings. Many of these studies in Saudi Arabia have explored B vitamins status in association with medical conditions or special population groups, such as diabetic patients, pregnant women and older adults.  Therefore, the current review provides an extensive review and critique to the literature of B vitamin status reported by research studies conducted in Saudi Arabia in order to outline the B vitamin of concern among Saudi population and provide a direction to future research. The current review informs future studies on Saudi population to plan their experiments and tackle issues reported from previous studies. Evidence-based recommendations, as well as identification of nutrients of concern, allow for proper allocation of the country’s resources, particularly those directed toward establishing nutrient reference values and/or toward programs targeting nutrient deficiencies among certain age groups.

Materials and Methods

A search was conducted on previously published studies on vitamin B status in Saudi Arabia. Databases (PubMed, Medline and Google Scholar) were searched for articles published between January 1980 to December 2022 using combinations of the terms “Saudi Arabia”, and “status”,  or“level” along with any the “vitamin B” names: vitamin B1, thiamine, thiamin, thiamine diphosphate (TDP), thiamine monophosphate (TMP), erythrocyte transketolase (ETK) essay, pyrophosphate or beriberi; vitamin B2, vitamin-G, riboflavin, erythrocyte glutathione reductase, flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN); vitamin B3, niacin, nicotinamide, nicotinic acid; B4, choline, NAD/NADH, NADP/NADPH, niacin flush, or pellagra; vitamin B5, pantothenic Acid, co-enzyme-A; vitamin B6, pyridoxine, or plasma pyridoxal phosphate (PLP); vitamin B7, biotin, vitamin H; vitamin B9, folic acid, folate, plasma homocysteine (HCY), red cell folate, tetrahydrofolate (THF), or dihydrofolate (DHF); vitamin B12, cobalamin, cyanocobalamin , methylmalonic acid, plasma HCY, megaloblastic anemia, macrocytic anemia, or pernicious anemia. The inclusion criteria were studies published during 1980 to 2022, Male and /or female with the age of ≥18 years in Saudi Arabia, and patients with chronic diseases such as diabetes mellitus (DM), hypertension (HTN), dyslipidemia, Irritable Bowel Syndrome (IBS), and asthma. Studies that include pregnancy/lactation, patients with heart failure, stroke, chronic obstructive pulmonary disease (COPD), patients on supplementation and lack of sufficient data were excluded. The data was then extracted by two researchers independently and summarized in a table to be used for result analysis.

Results

A total of 42 studies were obtained, only n=28 studies were included in this review (Figure 1). n= 15 studies were excluded due to pregnancy/lactation, severe chronic disease, or lack of sufficient data. Overall, the majority of studies obtained were mainly on folate and vitamin B12 status (Table 1). One study reported results of all the following B-vitamins (thiamin, riboflavin, pyridoxine, folate, and vitamin B12). Three studies included results for both folate and vitamin B12. None of the included studies reported niacin, pantothenic acid, or biotin concentrations or any related biomarker in Saudi Arabia.

Figure 1: Summary of Studies Included in the Review Click here to view Figure

Table 1: Studies on B vitamins status among Saudi Adults.

Thiamin (B1)

Four studies on thiamin status were conducted in Saudi Arabia. All of which were conducted in Riyadh except one study that included participants from different regions in Saudi Arabia. The earliest report on thiamin status among Saudis was a case-control study conducted in 2011 in Riyadh, where a total of n=231 adults (18-67 years old) included, but the majority had diabetes (n=43 type 1 diabetes; n= 162 type 2 diabetes).¹⁵  The study assessed both blood (thiamine, thiamine di-phosphate (TDP), thiamine monophosphate (TMP), and urinary thiamin concentrations; the functional indicator ETK activity in RBC was not assessed. Total blood thiamin was significantly higher among controls compared to diabetic patients: Control= 54.8±11.4 ng/mL; type 1 diabetes= 41.5±17.9 ng/mL; type 2 diabetes= 27.2±12.7 ng/mL).

Similarly, a cross-sectional study conducted on n=166 males and n=70 females in 2013 in Riyadh. Participants were recruited from primary care centers in Riyadh based on their metabolic syndrome status, it had more of a case-control design. The study assessed fasting blood thiamin derivatives (thiamine, TDP, TMP) and urinary thiamin concentrations. Mean ± SD participants’ age was 49.4 ± 16.5 and 53.7 ± 13.3 y in control group and metabolic syndrome groups, respectively.¹⁶  Thiamin concentrations were not shown for the total sample, but was presented by metabolic syndrome status, hypertension, and hyperglycemia. No significant differences were reported in any of the thiamin biomarkers between control groups and those with metabolic syndrome; mean ± SD total thiamin concentrations in whole blood of control vs. metabolic syndrome were 35.0 ± 1.8 vs. 31.3 ± 2.3 ng/ml, respectively.¹⁶  However, hypertensive participants (n=119) had lower concentrations of TDP and higher urinary thiamine concentrations compared to normotensive participants (n=117), whereas hyperglycemic participants (n=171) had lower blood TMP and TDP concentrations and higher urinary thiamine concentrations compared to normoglycemic participants (n=65). Rates of inadequate thiamin intake or thiamin deficiency were not reported.

A case-control study of 158 participants in Riyadh (n= 77 with type 1 diabetes and n=81 healthy controls) also assessed blood thiamine and its derivatives, as well as urinary thiamine concentrations.¹⁷ Controls were older than the cases and had higher total thiamin concentrations compared to control (42.9±15.1 ng/mL vs. 33.6±16.5 ng/mL). The only study on a large sample size of n=3,432 adults (18-87 y) was conducted between September 2019 and June 2021.¹⁸  The study selected participants living across the 13 administrative regions of Saudi Arabia (Riyadh, Makkah, Eastern Region, Northern Borders, Madinah, Jezan, Asir, Najran, Qassim, Tabuk, Hail, Al-Jouf, and Al-Baha). Serum thiamine pyrophosphate was determined using HPLC and 111 participants (3.2%) were classified as thiamin deficient (< 28 ug/L).¹⁸  Highest rate of thiamin deficiencies was among those aged 35–44 y. No significant differences were observed between men and women. Neither mean concentrations nor were ranges reported.¹⁸.

Riboflavin (B2)

Five studies assessed riboflavin status in Saudi population. Riboflavin, FMN, and FAD concentrations can be determined in plasma, serum, and erythrocytes to assess riboflavin status.  Riboflavin status can be also determined using its functional indicators glutathione reductase activity coefficient, EGRAC.¹ Three studies assessed the functional biomarker of riboflavin, glutathione reductase activity coefficient (EGRAC) and the other assessed serum or erythrocyte riboflavin concentrations.[7,19,20]  A study conducted in Riyadh city (located in the middle of KSA) reported that 17.1% of the males and 37.9% of the females (total n=502) had riboflavin deficient status, defined as EGRAC ≥ 1.30, ²⁰ whereas other studies reported a higher prevalence of deficiency among men in two other cities from different regions, Al-Hafouf (located in the East), Al-Ula (located in the West), and Jazan (located in the Southwest): 32.6%, 29.3%, and 17.8%, respectively.^7,19  Sample size from each city is not reported in the abstract and we could not access the full articles. It is worth noting that EGRAC <1.00 has been reported previously.²⁰ As in many of other older studies using older EGRAC methods and this has been criticized,²¹ Saudi females had higher rates of riboflavin deficiency compared to males. Rates of riboflavin deficiency among females from Al-Hafouf, and Riyadh (n=213), Al-Ula, Jazan were 41.5%, and 37.9, 35.9%, and 22.3%, respectively.⁷

A study on a large sample on Saudi adults reported that 37% had serum riboflavin < 2.3 μg/L (equivalent to 6.11 nmol/L), with males having higher rates of deficiency compared to females, 39.5% vs 34.2%.¹⁸ Currently, there is no cutoff of deficiency for serum/plasma riboflavin, FAD and FMN concentrations. Mean concentrations and ranges were not reported. It is not clear which form was assessed: total riboflavin or specific form: free riboflavin, FMN, or FAD.

Pyridoxine (B6)

Four cross-sectional studies have been conducted in three different cities in Saudi Arabia with one study included all the 13 regions in Saudi Arabia. A study conducted on n=51 male adults (n=20 of which considered from rural areas) with a mean± SD age of 33±6 years old living in Riyadh reported that 14 subjects (27.5%) had plasma pyridoxal phosphate (PLP) concentration < 30 nmol/L, indicating deficiency.²²  Seven of which also had a urinary 4-pyridoxic acid (4-PA) concentration < 3.0 µmol/L on average; no significant differences were found in all vitamin B6 vitamers between subjects from urban and rural areas. All participants had adequate pyridoxine intake based on 3-d food records (consecutive) and none had intakes below 1.3 mg/d.[22]  The mean BMI was 27.7 kg/m² and that n=30 (59%) of the participants were overweight or obese (BMI ≥ 25); BMI has been reported to be negatively associated with PLP concentrations.²³.

Another study that was also conducted in adult males (n=257), but in Dammam city, reported similar findings as none of the participants reported inadequate dietary B6 intake or had biochemical B6 deficiency based on mean plasma PLP <20 nmol/L and urinary 4-PA concentration < 3.0 mmol/d.[24] The third study was conducted in Al-Qassim region and included both males (n = 127; mean ± SD age 28.7±8.8 y) and females (n = 112; mean age 25.6±7.2 y). Both plasma and erythrocytes PLP concentrations were assessed, as well as dietary B6 intake [25]  This study also reported that none of the participants had inadequate dietary B6 intake <1.3 mg/d based 3-d food record (consecutive). None of the participants had plasma PLP <20 nmol or urinary 4-PA excretion under <0.3 µmol/d; 63.8% were classified as overweight or obese that might have impacted vitamin B6 status.²³

One study assessed pyridoxine status in a representative sample (n= 3,432 adults, mean age, 37.7 ± 11.7 years old).¹⁸  The study reported that only 57 participants (1.7%) had serum vitamin B 6 deficiency, however, a higher cut-off for deficiency was this study, 8.7 μg/L is the equivalent of 35.20 nmol/L that is higher than the commonly used cut-off of 20 nmol/L.¹⁸ Mean concentrations of PLP were not reported.

Folate (B9)

Folate status can be assessed using different biomarkers with serum/plasma folate being an easy and commonly used biomarker that reflects short-term status. Red blood cells folate is a good biomarker to reflect tissue folate contents, therefore long-term status.

The World Health Organization (WHO) has set criteria to define plasma/serum folate status as follows: elevated, >45.3 nmol/L; normal range, 13.5 – ≥ 45.3 nmol/L; possible deficiency, 6.8 – <13.4 nmol/L; deficiency, <6.8 nmol/L.[26]  In this review, six studies assessed folate status of Saudi adults.

A study conducted in 2002 to establish total plasma HCY reference intervals for Saudi adults living in Jeddah (males: n=642; females n=784; 20-69 y) reported that none of the participants had folate deficiency (defined as serum folate < 4.0 nmol/L).²⁷  Serum folate concentrations were higher in females than males, 14.40 ±5.26 nmol/L vs. 12.27± 4.84 nmol/L. The study also reported that n=84 (5.9%) subjects had serum folate concentrations between 4.22-6.36 nmol/L, indicating marginal status of deficiency. Proportion of participants with values less than 13.4 nmol/L (<6 ng/mL) have not been reported; those with folate concentrations < 13.4 nmol/L would be possibly deficient according the WHO criteria.[26]  It appears that there were sex-specific differences in BMI and blood pressure but values were not compared statistically.

A retrospective study conducted on 614 patients (males; n=228, (37.1%), females; n=386, (62.9%)) in Southern Saudi Arabia (Abha) found mean ±SD folate serum concentration was 27.3 ± 0.5 nmol/L and that 2.8% of the patients have serum folate < 10 nmol/L.²⁸  This study was based on patients who had folate test requested over a period of one year. The medical record of only 173 stated the reason for folate serum request and Anemia was the most common (45%); other medical history of these and other patients in the sample was not clear reducing the opportunity to understand the factors related to serum folate level.

A cross-sectional study in Riyadh was conducted among healthy adults where n=309 individuals (157 males,50.8%) and (152 females,49.2%) recruited and their serum folate was measured.[29]  Cut-off values were at: deficiency: < 3 ng/ml and <160 ng/ml, adequacy: ≥5 ng/ml and ≥200 ng/ml for serum and RBC folate concentration, respectively. The result showed that serum folate was significantly lower in males (7.3 ± 2.0 ng/ml) compared to females (14.6 ± 6.0 ng/ml).  However, only 1.9% of male participants had folate deficiency and 88.5% had adequate status, whereas 97.3% of females had adequate status and non had deficiency.²⁹

Another cross-sectional study in Riyadh assessed serum folate as part of investigating the relation of different type of nutrients with Temporomandibular disorder (TMD). The study measured serum folate among 67 TMD patients with average age of 45 years (range; 25 to 55 years).[30] The study showed that 22% (n=10) of the patients had low serum folate based on standard laboratory value, but this was not specified by the authors.³⁰  A study within institutionalized older adults performed a nutritional assessment in Makkah region.³¹ The study included 53 individuals (28 males, 52.8%) and (25 females, 47.2%) aged ≥ 60 years. The results showed that almost all subjects (96.23%) have normal folate level, while 3.77% of both males and females has low serum folate level (<4.6 ng/ml).³¹  A recent cross sectional study by Albalawi et al, 2022 was done in 13 Saudi regions included 3432 adults aged ≥18 years (mean age, 37.7 ± 11.7 years; women, 51.2%) to assess micronutrient deficiencies, and folate is one of them.¹⁸ The result of measuring serum folate showed that it is the second lowest vitamin deficiency (3.5%) and the levels were higher in men compared to women.

Cobalamin (B12)

Twenty-four studies have been conducted on vitamin B12 status in Saudi Arabia; seven of which targeted diabetic patients and one targeted patient with multiple sclerosis More than half (7out of 15) of studies on vitamin B12 were conducted in the city of Riyadh. The following biomarkers of vitamin B12 status are commonly used in population studies: serum/plasma vitamin B12 concentration, serum holotranscobalamin (holoTC) concentration, serum methylmalonic acid (MMA) concentration, plasma total HCY concentration.³²  None of the studies in Saudi Arabia assessed MMA or holoTC ^{18,27,28,31,33-42}

A cross-sectional study on 1426 participants (55% were females; 20-69 y) living in Jeddah was discussed in the folate section and reported that serum vitamin B12 mean±SD concentration was 239±73 pmol/L for males and 292±102 pmol/L for females; none of the participants had vitamin B12 <130 pmol/L.²⁷  Although the study included healthy participants and were medically examined, they were recruited from primary care centers and no health indicators were reported except for mean BMI and blood pressure that were indicative of overweight/obesity and elevated blood pressure in some age groups; and only age and gender reported in the sociodemographic information.²⁷

Three studies assessed B12 in healthy, non-smoker individuals, recruited from four Primary Health Care Centers within Riyadh (n=364).^33,37,38  The study reported median of serum vitamin B12 concentrations of 421 pg/mL (290.6–530.6 pg/mL) and 371.25 pg/mL (288.6–496.3 pg/mL) in children and adults, respectively.³³  Another study targeted diabetic adult patients with multiple sclerosis (n=110) recruited from four hospitals in Riyadh. The study reported that 65% of participants had adequate vitamin B12 status (200 – 900 pg/mL), whereas 30% had B12 < 200 pg/mL.⁴³ About 5% had B12 > 900 pg/mL which considered high by the author although there are no clear cut-offs for elevated vitamin B12. The study lacks a comparison group and diabetes medication history, making it difficult to draw conclusion on whether multiple sclerosis is associated with low vitamin B12. Khattab et al. 2016 measured vitamin B12 status in 53 Saudi elders aged 60 to 105 years living in Makkah and Taif city.³¹  As reported by Khattab et al 2016, 26% of participants had low serum vitamin B12 (<211 pg/ml in Makkah city laboratory and <240 pg/ml in Taif city laboratory). Fifty-eight percent of study participants had high HCY concentration (>16.20 umol/L).³¹

Studies after 2016 mostly targeted diabetic patients except for five studies by Al Musharraf et al 2020 and 2022, a study by Alkhaldy et al 2020, Albalawi et al 2022; which included non-diabetic participants and one study by Alshehri et al 2019 included participants suffering of migraine.

Vitamin B12 – Studies in participants with diabetes

Five studies in diabetic patients assessed vitamin B12 in diabetic patients treated with metformin[35,39,40,44]and one that did not target metformin users.³⁶

Almatrafi et al 2022 assessed 206 diabetic patients in Al-Noor Specialist Hospital in Makkah (n=85 males; n= 121 females) who were using metformin for at least six months.⁴⁰  The study reported that 17.5% of the patients had serum B12 levels <243 nmol/L.⁴⁰  The study had no control group to compare serum B12 among metformin users versus non-users and mean serum B12 was not reported. Lower rate of serum B12 deficiency (10%) was reported in Taif City (also in the Western region) among diabetic patients using metformin (n=347; mean age 58.10 ± 14.31 years). Mean serum B12 level was 464.99 ± 419.00 mg/dL.³⁹

Three studies in Riyadh reported different rates of B12 inadequacy, but used different cutoffs.  The first was conducted at King Abdulaziz Medical City reported that 3.6% of diabetic patients (n=11/307) who were using metformin had serum B12 < 150 pg/mL (the equivalent of 110.7 pmol/L).⁴⁴  The study also reported that 203 (66.1%) had borderline deficiency (150-399 pg/mL). The majority in this study were also females (62.2%) and mean age was 58.69±11.1 years.⁴⁴  Mean or median B12 were not reported and did not include control group either. The second study in Riyad conducted on diabetic patients using metformin (n=363; 57% females) reported the lowest number of B12 deficient as only two patients had serum B12 <200 pg/mL (=147.5612 pmol/L) and mean ±SD for all was 367 ± 139.95pg/mL; values of serum B12 in this samples ranged from 164.6-1288 pg/mL.³⁵  The third study compared metformin users (n=319) with non-metformin users (n=93) and reported an overall prevalence of 7.8% of serum B12 < 132.8 pmol/L.⁴⁵  The study reported mean concentration was 365.37±189.88 pmol/L among metformin users versus 313.69±141.84 pmol/L among non-users. Deficient serum vitamin B12 status (<132.8 pmol/L) was reported in n=30 (9%) of metformin users compared to n=2 (2%) of non-metformin users.

Only one retrospective study was conducted in Jazan (Southwest of Saudi Arabia) and examined patients attending the Jazan Diabetes & Endocrine Center with and without diabetic foot regardless of their metformin use.³⁶ However, the majority were using metformin (87%) as the hospital’s protocol was to assess B12 in metformin users. The study included 108 newly diagnosed cases with diabetic foot ulcers and 215 control participants with type 2 diabetes free of foot ulcers. Rate of serum B12 <148 pmol/L was higher among cases compared to controls (59% vs. 32%); mean serum concentrations.³⁶

What diet supported the adequacy?

Vitamin B12 – Studies in participants without diabetes

Almusharaf et al (2020, 2021 and 2022) assessed B12 intake and serum B12 in young females (n=346; 19-30 y) from university settings.^37,38,46  The majority had adequate vitamin B12 status with 0.6% were classified as deficient when serum B12 < 148 pmol/L was used, whereas 6% of the women were classified as B12 insufficient when serum B 12 ≤220 pmol/L cut-off was used.^37,38,46  About 92% of the participants consumed dietary intakes of the vitamin as recommended (> 2.4 mcg/d) and dietary vitamin B12 intake (Recommended Dietary Allowance> 2.4 mcg/d) was associated with lowers odd of having serum B12 insufficiency. Insufficiency of the vitamin was also associated with increased age, lower income level, and screen time (≥7 h/d).^37,38,46

A cross-sectional study assessed the correlation between Migraine (a headache disorder) and vitamin B12 status in 91 Saudi females with migraine and a control group of n=54 female participant.⁴¹  The mean ± SD of serum vitamin B12 in Migraine patients was 255 ± 13 pmol/L and control group had mean serum vitamin B12 of 258 ± 15pmol/L.⁴¹  The study concluded that vitamin B12 status was not significantly correlated with migraine. The study by Alkhaldy et al (2020) assessed vitamin B12 in n=543 patients retrospectively.²⁸  Patients’ data was collected from Aseer Central Hospital from either inpatient or outpatient clinics (Southern Saudi). Sampling was based on ordering of folate tests in the hospital from July 2018 to June 2019; no exclusion criteria were stated.²⁸  Mean vitamin B12 concentrations of these patients with folate test requests was not reported but 17.2% had vitamin B12 concentrations < 179 pmol/ L.²⁸  This was a very specific group, mainly patients, which explains the higher rate of B12 deficiency than previous studies.

A countrywide study has been conducted in 13 regions of Saudi Arabia (Riyadh, Makkah, Eastern Region, Northern Borders, Madinah, Jezan, Asir, Najran, Qassim, Tabuk, Hail, Al-Jouf, and Al-Baha) have found that; n= 259 (7.5%) of participants have vitamin B12 deficiency (serum B12 <187 pg/mL).¹⁸

Discussion

B vitamins play essential role in maintaining several body functions, including energy homeostasis, tissue growth and repair, and metabolic regulation. The objective of the current review was to identify the B vitamins status among Saudi adults as reported by original research studies since 1980. With the exception of vitamin B12 and folate, limited recent studies have assessed vitamin B1, B2 and B6.  Therefore, it is difficult to draw conclusions regarding the status of the vitamins B1, B2 and B6. In general, folate deficiency was observed in around 3% and vitamin B12 was observed in 10-17% of Saudi adults based on serum/plasma concentrations.

Overall, limited studies have assessed B vitamins in Saudi Arabia and the majority was not representative to Saudi population, the sample size was small, and/or the sample was collected from one city which was usually Riyadh city (the capital city of Saudi Arabia).  In addition, the studies have focused on type 2 diabetes due to 1) the influence of B vitamins in the incidence and the complications of type 2 diabetes, 2) the side effect of oral hypoglycemic agents in folate and vitamin B12 status, and 3) the increasing prevalence of type 2 diabetes in the last decade in Saudi Arabia.^47,49 

The majority of the studies have assessed the most common nutritional-deficiency anemias among female Saudi adults.  Evidence shows that the most common type of nutritional-deficiency anemia was iron deficiency anemia followed by vitamin B12 deficiency anemia and folate deficiency anemia. One key factor for B vitamins deficiency is dietary intake.  Poor dietary intake of vitamin B12 was observed in a previous study.⁵⁰  A recent study by Al-Musharaf et al 2020 found that the vitamin B12 intake among individuals with sufficient vitamin B12 status (>220 pmol/L) was higher than individuals with insufficient vitamin B12 status (≤220 pmol/L).  Among individuals with insufficient vitamin B12 status (≤220 pmol/L), 19% had estimated vitamin B12 intake below the Recommended Dietary Allowance.  Dietary habits changes including junk foods and rigorous diets including vegetarianism.^5,51,52  Studies that have assessed the status of B vitamins in Saudi Arabia were focused in Riyadh city and studies rarely reported dietary intakes. Some studies that reported dietary inadequacy of the group used the Recommended Dietary Allowance rather than the EAR, but overall rates of inadequacy were low. It is not clear whether the reported low status in some vitamins were due to inadequate dietary intakes or genetic factors affecting these vitamins absorption/metabolism.

In addition, there is inconsistency in the cut-off values used to define B vitamins deficiency. For example, vitamin B12 deficiency was defined as <148 pmol/L in 4 studies, <130 pmol/L in one study, and <180 pmol/L in two studies. In addition, there were some discrepancies in cut-offs were used in some studies to classify borderline or marginal status. Attention needs to be paid for units’ conversions and cut-offs used to define B vitamin status, especially for folate and vitamin B12 as some used the International System of Units and others used the traditional units. Several studies have reported the percent of sample below the cut-off values without providing the mean/median concentrations or range, making it challenging to compare studies particularly when cut-offs for deficiency is also different. Two studies reported on elevated vitamin B12 status (>701 or 664 pmol/L), but none of the studies reported on high folate status (>45 nmol/L). 

Over 40% of the studies in each vitamin were conducted in Riyadh (not the region), one study that included cities from 3 regions, and one study that reported data on a representative sample of all the 13 administrative regions. Studies on populations selected from the Western regions were about 28%. Accordingly, comparisons across regions could not be performed. The only study on a representative sample of Saudi adults did not report on the regional differences either. We speculate differences in B vitamin status between regions as Saudi regions have diverse dietary patterns influenced by age, gender, and geographical locations.^53-56

In 2000, folic acid fortification was introduced, while the other nutrients fortifications/ enrichments took place earlier. The earliest study on folate was conducted by Ardawi et al in 2002, post folic acid fortification, and aimed at establishing reference interval for HCY rather than assessing the change in folate status.²⁷ Evaluating the changes in B vitamin status before and after the intervention programs (fortifications/ enrichments) is an area to be examined.  This area was not the primary goal of the current review. Future studies could compare B vitamin status between fortified food consumers and non-consumers in Saudi Arabia.

Our review provides insights on the biochemical status of B vitamin in Saudi adults.  It covered four decades of published studies and focused on adults without chronic diseases (except for diabetes), minimizing the confounding effect of these abnormalities on the metabolism of B vitamin. However, our review has some limitations. Actual prevalence of B vitamin deficiencies could not be obtained due to issues related to lack of reporting, differences in cut-offs used, and lack of sufficient studies and representation. Many studies did not report mean/median concentrations and the range of the assessed biomarker, providing little data that could facilitate comparisons at the national or the international level. In addition, methods used need to be distinctly described as methodological differences can explain some of the variability in the results. Few studies were not included due to access issues or being published in predatory journals that could have added more information, but these were only limited studies.

Conclusion

Overall, here we provided a comprehensive review on the B vitamin status of Saudi adults that differed between regions and sexes. The results suggest the lack of deficiencies in vitamin B6 and folate, particularly after the implementation of mandatory folic acid fortification. Studies showed potential for inadequacies in vitamin B12 and riboflavin status, but more recent studies on apparently healthy population is needed. Data are insufficient to establish reference values for Saudi adults given the variability in populations selected, recruitment strategies, methodological and biomarker differences in biochemical assessment, and reporting issues.  Large national cohort studies are needed to assess the status of B vitamin and to assess the determinants of B vitamin insufficiency and/or deficiency in Saudi Arabia.  Such studies need to be representative and take into consideration healthy individuals. Including individuals with common noncommunicable diseases, such as diabetes and hypertension, require a through medical history and medications used. When reporting proportions of deficiency, studies need to also report the absolute concentrations. Moreover, rates suboptimal/marginal deficiency is also recommended to report for vitamins that have established cut-offs, as health issues might arise from early stages of inadequacy. Methodological details were missing in many studies and more details would facilitate accurate comparison across studies. It is recommended to use established cutoffs to define status as much as possible or report status using more than one commonly used cutoff to minimize comparability issues between studies.    

Acknowledgement

This project was supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2024R207), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Conflict of Interest

Authors disclose there is no conflict of interest.

Funding Sources

There is no funding sources.

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Abbreviations

AC: Activity
coefficient

DFU: Diabetic foot ulcer

DM: Diabetes mellitus

EGRAC: Glutathione
reductase activity coefficient

HCY: Homocysteine

MetS: Metabolic syndrome

NA: Non available

PLP: Plasma Pyridoxal
Phosphate

RBC: Red Blood Cell

SA: Saudi Arabia

T1DM: Type 1 diabetes mellitus

4-PA: urinary 4-pyridoxic acid