The Relationship of Macro–Micronutrient Intake with Incidence and Progressivity of Hypertension and Microalbuminuria

Abstract

Hypertension (HTN) and chronic kidney disease (CKD) are significant global health burdens, with microalbuminuria (MA) serving as a key early marker of renal damage and cardiovascular risk. While nutritional interventions are pivotal for management, the evidence for specific nutrients is often complex and inconsistent, creating challenges for clinical guidance. This review critically evaluates current evidence on the interaction among macronutrients, micronutrients, and established dietary approaches and their influence on the development and course of HTN and MA. Strong consensus is present regarding sodium restriction, increased intakes of potassium, and the implementation of dietary patterns like Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet to improve blood pressure and renal outcomes. Evidence favors protein moderation (approximately 0.8 g/kg/day), especially from plant sources, and emphasizes carbohydrate quality (e.g., high fiber, low glycemic index) over absolute quantity. The role of micronutrients is more nuanced; maintaining vitamin D sufficiency is protective, but intervention trials for many supplements, including B vitamins and antioxidant vitamins (C and E), have yielded inconsistent results. Several minerals, such as iron and selenium, exhibit a U-shaped risk curve where both deficiency and excess are detrimental, highlighting the risks of unselective supplementation. Ideal nutrition care prioritizes holistic dietary patterns over a focus on single nutrients. Clinical guidance should be founded on sodium reduction and potassium-rich foods, with personalized recommendations for protein and micronutrient supplementation based on an individual’s specific cardiovascular and renal profile. Future research must target nutrients with conflicting evidence to establish clear, evidence-based intake guidelines.

1. Introduction

Hypertension (HTN) represents the primary modifiable risk factor for cardiovascular disease (CVD). Uncontrolled HTN can result in numerous complications, including coronary heart disease, heart failure, stroke, hypertensive encephalopathy, chronic kidney disease (CKD), and hypertensive retinopathy [1,2]. Based on data from the World Health Organization (WHO) in 2019, approximately 1.13 billion individuals globally are affected by HTN, with a majority located in low-income countries. HTN results in approximately 8 million fatalities annually, with 1.5 million deaths occurring in Southeast Asia, where one-third of the population is affected by the condition [3]. HTN is also a degenerative disease with high morbidity and mortality rates in Indonesia. As per the Indonesian Basic Health Research data in 2018, the prevalence of HTN at the age of ≥18 years reached 34.1% with a higher prevalence in women (36.9%) compared to men (31.3%) [4].

Chronic kidney disease (CKD) is one of the most common complications of HTN, with microalbuminuria (MA) acting as a predictor of renal impairment and CKD progression [5]. MA denotes the increased excretion of low levels of albumin in urine, which may arise from kidney impairment, causing albumin to leak through the glomerular filtration barrier and impaired vascular function [6]. MA is also a crucial clinical marker for the early detection of renal damage in persons with type 2 diabetes (T2DM) [7]. Concurrent nephropathy in individuals with HTN and diabetes leads to a 37-fold increase in mortality risk [8]. Epidemiological studies indicated that identifying and monitoring patients with MA are crucial, as appropriate treatment can prevent or delay the onset of nephropathy [9].

Nutritional interventions are essential in the management of both HTN and MA as non-pharmacological treatments [10,11]. Numerous food and nutrient groups have been reported to be inversely associated with HTN risk, including fruits, legumes, whole grains, dairy products, fiber, and potassium. In contrast, those associated include sodium, dietary sugar, red meat, and processed meat. Systematic reviews of randomized controlled trials (RCTs) have demonstrated that particular dietary patterns, such as the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets, are correlated with decreased blood pressure (BP) in individuals [12,13]. Moreover, numerous studies have investigated the correlation between MA and various nutrients, highlighting dietary factors as crucial modifiable risk elements for mitigating the risk of MA and deterioration in kidney function among individuals with well-preserved estimated glomerular filtration rate (eGFR) at baseline [11,14]. This review critically evaluates current evidence on the interaction among macronutrients, micronutrients, and established dietary approaches and their influence on the development and course of HTN and MA, aiming to offer practical guidance in clinical practice.

2. A Glimpse of Hypertension (HTN) and Microalbuminuria (MA)

Hypertension (HTN) was generally defined as high BP after three consecutive measurements at two-minute intervals. When systolic blood pressure (SBP) and diastolic blood pressure (DBP) were classified differently, the highest category was used in assessing total cardiovascular risk [15]. HTN criteria can refer to the Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure or the American College of Cardiology/American Heart Association, as seen in

Table 1. Classification of hypertension based on JNC-8 and ACC/AHA for subjects aged 18 years or older.

Categories	Systolic Blood Pressure (SBP; mmHg)	and/or	Diastolic Blood Pressure (DBP; mmHg)
Joint National Committee (JNC) 8
Normal	<120	and	<80
Prehypertension	120–139	or	80–89
Stage 1 hypertension	140–159	or	90–99
Stage 2 hypertension	≥160	or	≥100
American College of Cardiology/American Heart Association
Normal	<120	and	<80
Elevated	120–129	and	<80
Stage 1 hypertension	130–139	or	80–89
Stage 2 hypertension	≥140	or	≥90

[16,17].

On the other hand, albuminuria refers to the abnormal presence of albumin in urine, classified into microalbuminuria (MA) and macroalbuminuria (proteinuria) [18]. MA indicates early endothelial damage within the renal glomeruli, defined by a persistent increase in urinary albumin levels ranging from 30 to 300 mg/day (20 to 200 µg/minute). Conversely, macroalbuminuria is characterized by an abnormal elevation in albumin excretion, defined as ≥300 mg/day [19].

Microalbuminuria (MA) does not directly induce cardiovascular events; instead, it serves as an indicator to identify individuals with elevated risk. MA results from injury to glomerular capillaries and may serve as an indicator of widespread endothelial dysfunction. Injury to the glomerular endothelium leads to a compromised filtration barrier, resulting in the loss of permselectivity and the subsequent passage of albumin into the filtrate, which ultimately becomes urine. This theory was demonstrated in a clinical study utilizing radioactively labeled albumin, revealing an independent correlation between MA and transvascular albumin leakage [20]. HTN influences urinary albumin excretion via general vascular impairment, including endothelial dysfunction and atherosclerosis, and directly through elevated glomerular pressure in the kidneys. HTN is associated with a higher prevalence of cardiovascular disease and contributes to the deterioration of renal function [21]. In diabetic patients, the glomerular endothelium is the primary site of damage that leads to the development of MA. The main issue related to this damage is the disturbance of the endothelial glycocalyx caused by mediators that are dysregulated in a diabetic context. The primary components include reactive oxygen species (ROS), vascular endothelial growth factor (VEGF), and proinflammatory cytokines. The communication impairment between endothelial cells and podocytes intensifies endothelial injury [22].

3. Core Nutrients with Strong Clinical Evidence and Consensus

3.1. Sodium and Potassium

The balance between sodium and potassium is a fundamental determinant of cardiovascular and renal health, as these minerals exert opposing effects and their dietary ratio is a critical predictor of BP and kidney function [23]. High sodium intake, notably exceeding the World Health Organization (WHO)’s recommendation of 2 g/day (equivalent to 5 g/day of salt), is a primary and well-established driver of HTN [24]. Mechanistically, excess sodium contributes to elevated BP through its effects on fluid volume and promoting arterial stiffness, and inducing endothelial dysfunction [25]. However, this effect of sodium is not uniform. It defines ‘salt sensitivity’—the degree to which BP responds to salt intake, an independent risk factor for cardiovascular and renal events [25]. This physiological trait is not uniform across populations; it varies significantly between individuals and is influenced by genetics, age, sex, and race [26]. Genetic predispositions play a significant role, with certain gene variants being more prevalent in specific ethnic groups, such as those of African American descent, contributing to a higher incidence of salt-sensitive HTN in that population [27]. Furthermore, salt sensitivity can be exacerbated by other dietary factors, such as high fructose consumption, which can impair renal sodium handling [28].

The exact mechanisms that contribute to HTN also directly impact kidney health and provide a clear link to MA. Elevated salt consumption can activate the local renin-angiotensin-aldosterone system (RAAS) within the kidneys, leading to oxidative stress, reduced nitric oxide (NO) availability, and glomerular injury, which is why understanding an individual’s salt sensitivity is essential for providing personalized advice [29,30,31]. Consequently, studies show a direct positive correlation between dietary salt intake and the presence of MA. This relationship is even more pronounced in individuals with a higher body mass index (BMI) [29,30].

In contrast, potassium is crucial for promoting vasodilation and lowering BP, primarily by counteracting sodium’s effects and activating sodium-potassium pumps in endothelial cells [32]. While its benefit for HTN is clear, the relationship between potassium and MA is more complex and appears to follow a U-shaped curve; moderate intake may reduce the risk of albuminuria, while excessive intake may increase it [33]. This risk from high potassium intake is particularly relevant for patients with pre-existing CKD [34]. Therefore, clinical guidance emphasizes achieving a moderate potassium intake, such as the 3.5–4.7 g per day recommended by the WHO and the United States, respectively, tailored to an individual’s overall health and kidney function [33,35,36].

3.2. Protein

The role of dietary protein in managing HTN and kidney health is complex, with benefits and risks depending critically on the quantity and the source of the protein consumed. For BP regulation, a moderate protein intake, generally aligned with the WHO’s recommendation of approximately 0.8 g/kg/day, appears to be beneficial [37]. This antihypertensive effect is primarily attributed to specific amino acids, such as arginine and tryptophan, which can enhance NO production. This, in turn, promotes vasodilation, relaxing the blood vessels and helping to lower BP [38].

High-protein diets can have the opposite effect, potentially increasing the risk of HTN. The mechanisms for this detrimental effect include inducing immune cell infiltration and inflammation in organs like the kidneys and blood vessels, and increasing calcium excretion, which can indirectly raise BP [39,40]. Critically, the protein’s source is a major differentiating factor. Diets high in animal protein, particularly processed meats, are strongly correlated with a higher likelihood of HTN due to their higher content of saturated fat, cholesterol, sodium, and nitrates. In contrast, plant-based proteins are often associated with a lower risk [41,42].

The adverse effects of a high protein load are especially pronounced in the kidneys, providing a direct link to MA. High protein consumption forces the kidneys to work harder, inducing a state of renal hyperfiltration [43]. In individuals with pre-existing kidney disease, this constant strain can accelerate glomerular scarring and the progression of renal failure. A recent observational study from Carballo-Casla et al. on older adults in Sweden showed that higher protein consumption is associated with improved survival compared to lower protein consumption in individuals with (CKD stages 1–3) and without CKD [44]. Moreover, plant-based, unprocessed proteins have been shown to slow eGFR decline [45]. Consequently, a key clinical guideline from organizations like the National Kidney Foundation is to restrict protein intake (to approximately 0.6 g/kg/day) for patients with CKD to slow the decline of kidney function and reduce proteinuria [20].

While the evidence for protein restriction in established CKD is strong, some studies have produced conflicting findings in other populations. For instance, one cohort study of Tasmanian individuals with insulin-dependent diabetes found that a higher protein intake was associated with a reduced prevalence of MA [20,46]. This finding may be attributable to the specific population studied or confounding dietary factors. Still, it underscores that most evidence supports protein moderation as a crucial strategy for preserving kidney function in at-risk individuals. Therefore, a balanced diet including adequate amounts of both animal and plant proteins is beneficial for general health, but this must be carefully tailored for individuals with or at risk for kidney disease.

3.3. Carbohydrates

Dietary carbohydrate quantity and quality exert essential effects on cardiometabolic and renal health. High carbohydrate intake, particularly from refined and rapidly absorbed sources, is associated with obesity, insulin resistance, and elevated BP. Diets with a high glycemic index or load induce postprandial hyperglycemia and compensatory hyperinsulinemia, which can increase sympathetic activity, sodium retention, and vascular stiffness [47,48]. Epidemiologic studies in China indicate that both very high and very low proportions of carbohydrate intake are linked to a higher risk of new-onset HTN. In contrast, moderate intake—around 50–55% of total energy—appears to be associated with the lowest risk [49]. This U-shaped pattern likely reflects the adverse effects of excessive refined carbohydrate consumption at one extreme and the metabolic consequences of high-fat or high-protein substitution at the other.

Beyond total carbohydrate intake, the quality of carbohydrate sources is a critical determinant of vascular outcomes. South Korean populations with a higher carbohydrate quality index—characterized by greater intake of whole grains, fruits, and vegetables and lower intake of refined grains, added sugars, and liquid carbohydrates—show lower prevalence of obesity and HTN [50]. High-quality carbohydrates provide fiber, micronutrients, and antioxidant phytochemicals that improve endothelial function and insulin sensitivity, reduce oxidative stress, and promote satiety, contributing to lower BP. Conversely, low-quality carbohydrates increase postprandial glucose excursions and oxidative stress, impairing NO-mediated vasodilation [49,51,52,53].

Carbohydrate quality also has implications for kidney health. Obesity and insulin resistance, frequently driven by high intake of refined carbohydrates, accelerate glomerular hyperfiltration and contribute to MA and CKD progression. While low-carbohydrate diets (LCDs) can improve short-term metabolic parameters and support weight reduction, they often increase protein intake, which may impose additional intraglomerular pressure and raise the risk of renal hyperfiltration [54]. Some studies report transient increases in eGFR during LCD interventions, but this likely reflects hyperfiltration rather than improved renal function. Sustained adherence to balanced diets emphasizing high-quality carbohydrate sources—rather than extreme carbohydrate restriction or excessive protein substitution—appears to offer the most favorable profile for both BP regulation and renal protection [55]. Overall evidence indicates that carbohydrate quality is more important than absolute quantity for preventing HTN and renal microvascular injury. Diets centered on whole grains, fruits, and non-starchy vegetables support cardiometabolic stability, whereas patterns dominated by refined carbohydrates or excessive restriction may adversely affect both vascular and renal outcomes.

3.4. Established Dietary Patterns

Modern clinical guidance for managing HTN and its renal complications, such as MA, has shifted from focusing on single nutrients to recommending holistic dietary patterns. This approach is favored because the synergistic effects of various food components in a whole diet are more potent than isolated interventions. The most evidence-based nutritional patterns—namely the DASH diet, the Mediterranean diet, and plant-based diets—all share common principles, including a high intake of whole foods, fruits, and vegetables, and a low intake of sodium and processed products [56,57]. Their success lies in simultaneously addressing multiple pathological pathways, including vascular function, inflammation, and oxidative stress [58].

The DASH diet, which emphasizes fruits, vegetables, and low-fat dairy while limiting sodium and saturated fat, is highly effective for cardiovascular and renal health. A meta-analysis of 30 randomized controlled trials confirmed that the DASH diet significantly reduces systolic and diastolic blood pressure by approximately 3.2 mmHg and 2.5 mmHg in adults with and without pre-existing HTN [59]. This benefit extends to kidney health, as further meta-analyses demonstrate that high adherence to the DASH diet is associated with a significantly lower risk of developing MA [60]. In patients already diagnosed with CKD, higher adherence has also been linked to a lower urine albumin-to-creatinine ratio (UACR), a key marker of kidney damage [61].

Similarly effective is the Mediterranean diet, renowned for its broad cardiovascular benefits. It is rich in monounsaturated fats, omega-3 fatty acids, and polyphenols that collectively improve endothelial function while reducing inflammation and oxidative stress [62]. Multiple meta-analyses confirm its effectiveness for blood pressure management, showing that adherence to the Mediterranean diet significantly lowers BP and is associated with a 13% lower odds of developing HTN, proving more effective than a usual diet [63,64]. These benefits extend to renal health, as further evidence from meta-analysis and secondary analysis of randomized trials demonstrates that the diet is linked to a significantly reduced risk of diabetic nephropathy and can lower the UACR, particularly in high-risk patients with both T2DM and obesity [65,66].

In addition, plant-based diets (PBDs), which are naturally rich in beneficial nutrients like potassium and fiber while low in sodium and saturated fat, are increasingly recognized for improving both BP and markers of kidney health. Meta-analyses confirm that PBDs effectively lower BP, with the most significant reductions seen in patterns like the DASH and lacto-ovo vegetarian diets, suggesting that eliminating animal products is not essential for a beneficial effect [67]. The evidence for strict vegan diets is more varied. At the same time, some analyses have reported a pronounced BP reduction [68], while others have found a more negligible, non-significant effect, a discrepancy potentially due to short study durations or healthy comparator diets [69]. Beyond blood pressure, PBDs also show promise for renal health. Reviews of the literature indicate that plant-based and vegetarian low-protein diets are associated with significant decreases in proteinuria and lower urinary albumin excretion rates, a finding supported by both interventional and observational studies [70,71].

Table 2. Key components and health effects of major dietary patterns on HTN and MA.

Dietary Pattern	Key Components	Primary Mechanisms	Established Benefits for HTN & MA
DASH Diet	Rich in fruits, vegetables, and low-fat dairy; low in sodium, saturated fat, red meat, and sweets.	Provides high levels of potassium, magnesium, and calcium; is high in fiber and has an anti-inflammatory effect.	Significantly lowers BP, reducing the intraglomerular pressure contributing to kidney damage and HTN.
Mediterranean Diet	High intake of olive oil, nuts, fish, legumes, vegetables, and fruits; low in red/processed meat and sweets.	High in monounsaturated fats, omega-3s, antioxidants, and polyphenols; improves endothelial function and reduces inflammation and oxidative stress.	Highly effective for blood pressure control and has demonstrated benefits for kidney health, including a lower risk of CKD and a decreased UACR.
Plant-Based Diets	Rich in fruits, vegetables, whole grains, and legumes; eliminates meat (vegetarian) or all animal products (vegan).	Typically lower in sodium and saturated fat, and higher in potassium, magnesium, and fiber. The lower acid load from plant proteins may also benefit kidney health.	Effective for lowering BP, plant-based low-protein diets are associated with significantly decreasing proteinuria and lower urinary albumin excretion rates.

summarizes the major dietary patterns, key components, and their health effects on HTN and MA.

4. Nutrients with Promising but Inconsistent Evidence

4.1. Antioxidant Vitamins: Vitamin C and E

Vitamin C (ascorbic acid) is a water-soluble antioxidant abundant in fruits, vegetables, and fortified foods. It scavenges superoxide anions, inhibits peroxynitrite formation, and restores tetrahydrobiopterin, an essential endothelial nitric oxide synthase (NOS) cofactor, thereby enhancing NO-mediated vasodilation [72]. While observational data link higher vitamin C levels to lower BP, evidence from intervention trials is nuanced. Meta-analyses show that vitamin C supplementation significantly reduces BP in hypertensive individuals. Still, the evidence does not support a similar albuminuria or BP benefit in other populations [72,73,74]. However, this benefit appears to be population-specific, as a meta-analysis focusing on the general, normotensive population found no significant BP reduction from vitamin C supplementation [75]. Regarding kidney health, the evidence is not supportive; a meta-analysis in patients with diabetes and albuminuria found that supplementation with antioxidant vitamins, including vitamin C alone, had no significant effect on reducing albuminuria or BP [76].

Similarly, vitamin E (α-tocopherol) is a lipid-soluble antioxidant that protects cellular membranes from lipid peroxidation and supports endothelial function [77]. Despite this protective mechanism, multiple meta-analyses consistently show that vitamin E supplementation does not significantly alter SBP or DBP in either hypertensive or normotensive populations [73,75]. In contrast, regarding kidney health, a meta-analysis focused on patients with diabetes and albuminuria found that while antioxidant vitamins overall did not affect BP, a subgroup analysis revealed that vitamin E supplementation alone could significantly reduce albuminuria [76].

The vascular mechanisms targeted by vitamins C and E are also relevant to renal injury. Oxidative stress and inflammation contribute to glomerular and tubular cell apoptosis, podocyte foot-process effacement, and loss of filtration-barrier integrity—hallmarks of MA and early CKD [78,79,80]. Both vitamins have demonstrated renoprotective effects in experimental and short-term clinical settings: supplementation reduces albuminuria, proteinuria, and markers of oxidative damage, particularly among patients with diabetes or HTN [76]. An extensive population study utilizing data from the National Health and Nutrition Examination Survey (NHANES) further shows that higher circulating vitamin C levels are associated with lower risk of albuminuria and reduced incidence of CKD [81]. Nevertheless, long-term high-dose antioxidant therapy is not recommended, as excessive vitamin E can interfere with other fat-soluble antioxidants [82,83], and megadoses of vitamin C may increase oxalate accumulation and kidney-stone risk [84]. Future research should define optimal physiological ranges and clarify whether combined antioxidant strategies within whole-food dietary patterns yield more stable improvements in vascular and kidney outcomes.

4.2. B Vitamins and Homocysteine

B vitamins are essential cofactors in multiple metabolic pathways, including amino acid metabolism, red blood cell synthesis, and DNA methylation [85,86]. Among them, thiamine (B1), riboflavin (B2), pyridoxine (B6), folate, and cobalamin (B12) have been most closely linked to vascular and renal health through their collective influence on homocysteine metabolism and endothelial function. Elevated plasma homocysteine is recognized as a modifiable risk factor that promotes oxidative stress, endothelial dysfunction, and vascular stiffness—pathophysiologic processes shared by HTN and MA [87].

The effect of B vitamin supplementation on BP appears highly dependent on the population studied. Meta-analyses show that folic acid supplementation significantly reduces BP in adults with essential HTN, an effect that is especially pronounced in those with genetic variations in homocysteine metabolism (the MTHFR TT genotype) [73]. In this same genetic subgroup, B2 supplementation has also proven effective at lowering BP [88]. In contrast, these benefits do not seem to apply to individuals with normal BP, as a meta-analysis in normotensive populations found that supplementation with folic acid and other B vitamins (B1, B2, B6) had no significant effect [76]. While many observational studies report inverse associations between B vitamin levels and HTN risk, findings are inconsistent, with some studies showing no association or even a paradoxical positive correlation [85,89,90,91,92]. Furthermore, thiamine (B1) intake has displayed a U-shaped association with HTN risk, indicating potential harm from both deficiency and excess [93].

Regarding kidney health, there is a strong mechanistic link between B vitamin status and renal injury. Both thiamine deficiency and hyperhomocysteinemia are implicated in the degradation of the glomerular barrier, which increases vascular permeability and leads to albumin leakage [94,95]. Despite this, clinical trials have yielded disappointing results. A major Cochrane review concluded that while B vitamin supplementation successfully lowered homocysteine levels in patients with diabetic kidney disease (DKD), it had little or no effect on the progression of the disease, including no significant change in urinary albumin excretion or BP [90]. Although some isolated studies suggest a modest benefit from thiamine supplementation on albuminuria, this finding was inconsistent across all B vitamin therapies, indicating that the evidence does not support routine high-dose supplementation beyond correcting a deficiency [94,95,96].

4.3. Vitamin D

Vitamin D is a fat-soluble vitamin essential for the human body. It can directly or indirectly regulate various physiological functions by binding to its specific vitamin D receptor (VDR) [97]. Experimental models show that VDR signaling suppresses renin expression and downregulates the RAAS, providing a plausible pathway by which adequate vitamin D status may lower BP. In parallel, vitamin D influences endothelial function and inflammation, and these vascular actions provide mechanistic links to systemic HTN and glomerular health [98]. Animal studies and VDR-knockout models consistently demonstrate that the absence of VDR activity increases renin and angiotensin II and worsens vascular and renal injury. At the same time, active vitamin D analogs reduce mesangial proliferation, podocyte hypertrophy, and proteinuria in renal injury models [99].

Vitamin D status is consistently associated with BP and kidney health, though evidence from supplementation trials is conflicting. Large meta-analyses of observational studies show a strong inverse and dose-dependent relationship, where higher serum vitamin D levels are linked to a significantly lower risk of developing HTN [100]. While this association is clear, intervention trials indicate a more modest effect, with umbrella meta-analysis finding that vitamin D supplementation produces a small but statistically significant reduction in BP, suggesting its role as an “efficient adjuvant” therapy [101]. On the other hand, several recent high-level reviews have found no significant effect. An umbrella review of meta-analyses in adults with essential HTN reported no significant impact of vitamin D on BP. This conclusion was also found in a meta-analysis of the general, normotensive population. It was further corroborated by a 2025 meta-analysis in hypertensive patients, which found that vitamin D supplementation had no significant effects on SBP or DBP [73,75,102].

The benefits of supplementation appear more pronounced for specific markers of kidney damage; in patients with DKD, the most consistent finding across multiple meta-analyses is a significant reduction in proteinuria and urinary albumin excretion [103,104]. However, this improvement in proteinuria does not appear to extend to other key renal function markers, such as eGFR or serum creatinine, which were not significantly affected in the pooled analyses [103].

4.4. Minerals: Magnesium and Calcium

Magnesium and calcium are essential minerals whose balance is critical for regulating vascular tone and BP. Their effects are often interconnected, with adequate intake crucial for cardiovascular and renal health. Magnesium plays a vital protective role, and its deficiency is linked to a higher risk of both HTN and CKD [105,106]. Multiple meta-analyses confirm that magnesium supplementation significantly reduces both SBP and DBP in hypertensive individuals, with its primary mechanism being its function as a natural calcium channel blocker that promotes vasodilation [102,107,108,109]. This benefit appears specific to at-risk groups, as meta-analyses focused on the normotensive population have found no significant effect [75]. Beyond its impact on BP, magnesium also shows promise for kidney health. While observational evidence linking low magnesium to MA through oxidative stress is inconsistent [110,111,112], an RCT in patients with diabetic nephropathy demonstrated that magnesium supplementation significantly reduced the urinary albumin excretion rate [113].

Calcium’s role in BP regulation is paradoxical; insufficient dietary intake can trigger hormonal responses via the parathyroid hormone (PTH) and the RAAS, leading to increased intracellular calcium, vasoconstriction, and consequently, higher BP [114,115]. Like magnesium, calcium supplementation depends on an individual’s baseline HTN status. Meta-analyses show that supplementation is an effective complementary therapy for significantly reducing BP in hypertensive patients. Still, this benefit does not extend to the normotensive population [75,102]. While the role of calcium in BP regulation is well-documented, a direct and consistent relationship between dietary calcium intake and MA in the general population has not been established in the current literature. Most research investigating a potential link between calcium and kidney-related outcomes has been conducted in pregnancy, where calcium metabolism is altered and linked to conditions like pre-eclampsia. However, these specialized findings are not readily generalizable to the broader population with chronic HTN or CKD. Therefore, the discussion on calcium primarily focuses on its impact on HTN.

5. Nutrients with Emerging or Highly Controversial Roles

5.1. Iron

Iron deficiency can impair crucial enzymatic functions and lead to chronic inflammation, which causes endothelial dysfunction and contributes to the development of HTN. Conversely, excess iron is a powerful catalyst for ROS formation, leading to widespread cellular damage, lipid peroxidation, and endothelial injury, which promotes atherosclerosis and increases BP. Consequently, studies show that while a moderate iron intake is associated with a lower risk of HTN, elevated iron stores, often indicated by high serum ferritin levels, are linked to a significantly increased risk [116,117]. Cross-sectional studies suggest a positive association between elevated ferritin concentrations, which signify iron overload, and the risk of HTN, implying a potential interaction between iron levels and HTN. Moreover, concerns exist regarding the potential nephrotoxic effects of iron supplements, particularly when administered in high doses or in conjunction with conventional medications. Further studies are required to confirm the detailed mechanisms [118].

The exact iron-induced mechanisms that damage the systemic vasculature are particularly harmful to the delicate microvasculature of the kidneys, providing a strong mechanistic link to MA. Although direct clinical evidence is still emerging, the relationship is highly plausible. Elevated serum ferritin is frequently observed in patients with glomerular disease and proteinuria, which is likely explained by iron’s capacity to induce oxidative stress directly at the glomerulus, disrupting the filtration barrier and leading to protein leakage [119]. While ferritin can also be a general marker of inflammation, studies have shown a weak correlation with other inflammatory markers like hs-CRP in this context, suggesting that direct iron-mediated injury is the more probable mechanism [119,120].

5.2. Zinc

Zinc is an essential mineral whose protective effects on the cardiovascular and renal systems are primarily attributed to its powerful antioxidant properties and critical role in NO synthesis. Zinc’s influence on BP is directly linked to its support of endothelial function. It is a key component of enzymes that scavenge superoxide radicals, thereby reducing oxidative stress in the vasculature. Furthermore, zinc is essential for the proper function of NOS, the enzyme responsible for producing NO. In states of zinc deficiency, reduced NOS activity leads to lower NO bioavailability, impairing the ability of blood vessels to relax and leading to endothelial dysfunction and HTN [121,122].

This exact protective mechanism is fundamental to zinc’s role in kidney health. Reducing oxidative stress and supporting endothelial function are particularly crucial for protecting the delicate microvasculature of the glomeruli [123]. Evidence from clinical studies shows that zinc supplementation can decrease MA, especially in individuals with T2D—a condition characterized by high oxidative stress. Preclinical studies in animal models further clarify this link, demonstrating that zinc deficiency can exacerbate kidney damage by promoting the expression of fibrotic factors like TGF-β, leading to tubulointerstitial fibrosis [124].

5.3. Selenium

Selenium is a trace mineral demonstrating a narrow therapeutic window, where maintaining a precise balance is crucial for cardiovascular and renal health. Both its deficiency and excess have been linked to adverse outcomes, establishing a classic U-shaped relationship. Selenium is essential for health in sufficient amounts, acting as a necessary cofactor for key antioxidant enzymes like glutathione peroxidase (GPx). These enzymes protect the body from ROS, inhibit lipid oxidation, and may help prevent the formation of atherosclerotic plaques. By safeguarding cells from oxidative damage, adequate selenium status is vital for maintaining vascular health [125]. However, once selenium intake exceeds the body’s requirements, it can become toxic and paradoxically promote the conditions it helps prevent at lower levels, as multiple studies have associated higher selenium levels with an increased risk of HTN [125,126].

High levels of selenium can induce endoplasmic reticulum (ER) stress in endothelial cells, which leads to a harmful combination of decreased NO bioavailability and increased ROS release. This endothelial injury particularly damages the delicate glomerular filtration barrier in the kidneys. By injuring glomerular endothelial cells, excess selenium can directly cause albuminuria. Furthermore, high selenium levels can inhibit other protective enzymes like thioredoxin reductase, leaving the kidneys more vulnerable to damage from oxidative stress and ischemia [127].

Given this U-shaped curve, the clinical implication is to ensure dietary adequacy—meeting the recommended daily intake of 55 μg—rather than pursuing high-dose supplementation [128]. Supplementation should be approached with significant caution and reserved for cases of diagnosed deficiency, as the risk of harm from excess intake is substantial.

5.4. Phosphorus

While high phosphorus levels are clearly linked to vascular damage and are a primary target for management in CKD, some observational studies have surprisingly associated higher dietary intake with lower BP. Mechanistic and clinical data show that high phosphorus loads can harm vascular health. In animal studies, phosphorus has been shown to elevate BP and induce endothelial dysfunction. In humans, high phosphorus intake, particularly from food additives, is linked to diminished endothelial function and an increased risk of adverse cardiovascular outcomes, including vascular calcification. A proposed mechanism involves the hormone FGF23, which regulates phosphorus and may also enhance sodium retention in the kidneys, thereby raising BP [129]. Because of these harmful effects, regulating dietary phosphate absorption is essential at all stages of CKD to prevent progression.

The paradoxical findings that higher phosphorus intake correlates with lower BP in some studies are likely explained by confounding dietary factors. The underlying mechanism for this observation remains unclear. However, whole foods naturally rich in phosphorus, such as dairy products, are also excellent sources of BP-lowering minerals like calcium and magnesium. In these cases, phosphorus may indicate a diet rich in these other beneficial cations, rather than the cause of the benefit itself. Therefore, the crucial distinction lies in the source of the phosphorus [130,131]. The harm is most strongly associated with highly absorbable inorganic phosphates used as additives in processed foods, whereas the paradoxical beneficial association is seen with organic phosphorus from nutrient-dense whole foods. The clinical takeaway is not to increase phosphorus intake for BP control but to limit phosphorus from food additives. A low-phosphate diet and phosphate binders remain essential for any patient with CKD, as intermittent dialysis is insufficient for clearing the body’s phosphate load [132].

Table 3. Summary of evidence and clinical recommendations for individual nutrients for HTN and MA.

Nutrient/ Factor	Strength of Evidence	Effect on Hypertension (HTN)	Effect on Microalbuminuria (MA)	Clinical Recommendation
Sodium	Strong	High sodium intake is a primary and well-established driver of HTN.	Elevated salt consumption can activate the local RAAS within the kidneys, leading to glomerular injury.	Prioritize reducing sodium intake towards the WHO recommendation of 2 g/day.
Potassium	Strong	Crucial for promoting vasodilation and lowering BP by counteracting sodium’s effects.	The complex relationship appears to follow a U-shaped curve where moderate intake may be protective, but excessive intake may be harmful.	Achieve adequate intake through diet (3.5–4.7 g/day) while exercising caution in patients with compromised renal function.
Protein	Moderate	The role is complex, with benefits and risks depending on the quantity and the source (plant vs. animal).	High-protein diets are harmful and accelerate kidney function decline by causing hyperfiltration and glomerular scarring.	Recommend moderation (~0.8 g/kg/day), favoring plant-based and lean protein sources. Protein restriction is crucial for patients with CKD.
Vitamin D	Moderate (Associative)	Observational studies show a strong inverse relationship between vitamin D levels and HTN risk, but evidence from intervention trials is conflicting.	The benefits of supplementation appear more pronounced for kidney health, with evidence showing a significant reduction in proteinuria.	Consider its role as an “efficient adjuvant” therapy. The goal is to correct the deficiency, not pursue high-dose supplementation.
Carbohydrate	Moderate to Strong	Quality is more critical than quantity; diets high in fiber and low in glycemic index are beneficial.	High fructose intake is linked to glomerular HTN and renal injury, while fiber is protective.	Prioritize high-quality, high-fiber, low-glycemic-index carbohydrates while limiting added sugars and refined grains.
Antioxidant Vitamins (C & E)	Weak & Conflicting	Vitamin C has a modest benefit in hypertensive populations, but not normotensive ones. Vitamin E has no significant effect on BP.	Evidence does not support a benefit for Vitamin C. Vitamin E supplementation alone may significantly reduce albuminuria.	Long-term, high-dose supplementation is not recommended; nutrients should be obtained from whole foods.
B Vitamins & Homocysteine	Weak & Conflicting	Folic acid reduces BP in hypertensive populations (especially with MTHFR variants), but B vitamins do not affect normotensive individuals.	Despite successfully lowering homocysteine, B vitamin supplementation has little to no effect on urinary albumin excretion in clinical trials.	The evidence does not currently support routine high-dose supplementation beyond correcting a deficiency.
Magnesium & Calcium	Promising but Inconsistent	Supplementation benefits hypertensive individuals but not the normotensive population.	Magnesium may reduce urinary albumin excretion. A direct link between calcium intake and MA is not established.	Prioritize dietary sources. Supplementation can be considered for hypertensive patients.
Iron & Selenium	Controversial (U-shaped)	Both deficiency and excess are detrimental to vascular health and are linked to HTN risk.	The U-shaped risk curve applies to renal health, as both deficiency and excess can promote oxidative stress in the kidneys.	Supplementation should be avoided unless a true deficiency is diagnosed, due to the narrow therapeutic window and risk of toxicity.
Phosphorus	Controversial	The “phosphorus paradox”: harm is most strongly associated with inorganic phosphates from food additives, not organic phosphorus from whole foods.	Phosphate control is a cornerstone of management in Chronic Kidney Disease (CKD) to slow its progression.	Limit phosphorus from food additives. For any patient with CKD, a low-phosphate diet is essential.

presents the summary of evidence and clinical recommendations for patients with HTN and MA.

6. Considerations and Future Perspectives

When interpreting the findings of this review, several limitations should be considered. First, this work is a comprehensive narrative review and not a systematic one, meaning it does not follow a predefined, reproducible search protocol such as PRISMA. This approach risks selection bias, and some relevant studies may have been unintentionally omitted. Furthermore, this review provides a qualitative synthesis of the evidence without performing a quantitative meta-analysis to statistically pool the data. Therefore, conclusions regarding the magnitude of effects for each nutrient are descriptive rather than based on a single, aggregated estimate.

The conclusions are also inherently limited by the nature of the available primary literature. The studies discussed are highly heterogeneous in their design, patient populations, intervention durations, and nutrient dosages, which makes drawing universal conclusions challenging and likely contributes to the conflicting findings for many nutrients. This review also highlights the frequent discrepancy between observational studies, which suggest strong associations, and RCTs, which often fail to show a causal benefit for supplementation. It is also essential to consider the influence of regional and cultural variability when interpreting nutritional evidence. Dietary patterns differ substantially across populations, including the dominant carbohydrate and fat sources, levels of food processing, and micronutrient fortification practices. Environmental factors such as sunlight exposure, altitude, and food availability further contribute to differences in nutrient status, particularly for vitamin D and mineral intake. Genetic polymorphisms affecting salt sensitivity, lipid metabolism, and homocysteine regulation may also modify individual responses to specific nutrients. These variations highlight the importance of contextualizing dietary recommendations and underscore the need for regionally adapted strategies to prevent HTN and kidney disease.

7. Conclusions and Suggestions

In conclusion, the most compelling message from this comprehensive review is the superior efficacy of whole dietary patterns, such as the DASH and Mediterranean diets, over single-nutrient supplementation for managing HTN and protecting renal health. The evidence suggests a clear hierarchy of nutritional strategies. The cornerstones of management remain well-established principles: the reduction in dietary sodium and an increased intake of potassium-rich foods. Beyond this, while some nutrients like magnesium show promise, their evidence is often inconsistent and dependent on an individual’s baseline status. For other micronutrients, particularly trace minerals like iron and selenium, caution is warranted due to their narrow therapeutic windows and U-shaped risk curves. Ultimately, this review underscores that a one-size-fits-all approach is inadequate, and effective nutritional management requires personalization based on an individual’s clinical status, deficiencies, and health conditions.

Translating these findings into actionable guidance, several suggestions for clinical practice and future research emerge. Clinicians should prioritize counseling patients on foundational, pattern-based advice, such as reducing the intake of processed foods to lower sodium and increasing the consumption of fruits and vegetables. Based on the current evidence, routine high-dose supplementation with isolated nutrients like antioxidant vitamins is not justified for BP control or renoprotection and may carry risks. A more prudent approach would be to screen for and correct specific deficiencies, such as vitamin D, to restore sufficiency rather than achieve supraphysiological levels.

Future research should prioritize long-term, high-quality RCTs that assess clinical endpoints rather than only short-term biomarker changes to address the inconsistencies and gaps identified in this review. There is a critical need for more head-to-head trials directly comparing the effectiveness of different dietary patterns on blood pressure and MA progression. Given that much of the existing research is BP-centric, future studies must be designed to specifically investigate the direct effects of nutrition on albuminuria, independent of BP changes. Finally, research should continue to move beyond single-nutrient models to explore the synergistic effects of nutrients within whole-food matrices across diverse ethnic and geographic populations.