Potassium helps bones by increasing the absorption of both Calcium and Vitamin D – Feb 2024

Potassium: A Frontier in Osteoporosis

Horm Metab Res DOI: 10.1055/a-2254-8533
Widhilika Singh , Poonam Kushwaha

Osteoporosis is a significant public health concern, particularly in aging populations, leading to fractures, decreased mobility, and reduced quality of life. While calcium and vitamin D have long been recognized as essential for bone health, emerging research suggests that potassium may play a crucial role in maintaining bone density and preventing osteoporosis. This manuscript explores the relationship between potassium and osteoporosis, delving into the mechanisms, epidemiological evidence, and potential therapeutic implications of potassium in bone health. Furthermore, the manuscript discusses the sources of dietary potassium, its impact on bone metabolism, and the future directions in research and clinical practice regarding potassium’s role in osteoporosis management.
 Download the PDF from Vitamin D Life

The following text is poorly formatted - You will probably find the PDF to be easier to read

Introduction
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, structural deterioration of bone tissue, and an increased susceptibility to fractures. It is a major global health concern, par­ticularly as the aging population continues to grow [1]. Osteopo­rosis is often referred to as the “silent disease” because it progress­es without symptoms until a fracture occurs. The primary hallmark of osteoporosis is reduced bone density and altered bone microar­chitecture, leading to bones becoming fragile and prone to frac­tures, especially in the hip, spine, and wrist [2].
Epidemiology
Osteoporosis is a global health issue affecting both men and women. According to the International Osteoporosis Foundation, it is estimated that worldwide, one in three women over the age of 50 and one in five men will experience an osteoporotic fracture dur­ing their lifetime. The prevalence of osteoporosis varies across re­gions, with higher rates observed in postmenopausal women and the elderly [3,4].
Causes and Risk Factors
Osteoporosis results from an imbalance in bone remodeling, a con­tinuous process involving bone resorption by osteoclasts and bone formation by osteoblasts. Several factors contribute to this imbal­ance [5-7]:

• Aging: Osteoporosis is more common in older adults due to the natural aging process, which leads to decreased bone density.
• Hormonal Changes: Postmenopausal women are at a higher risk of osteoporosis due to a decline in estrogen levels, which plays a crucial role in bone health.
• Genetics: A family history of osteoporosis can increase one's risk.
• Nutrition: Inadequate intake of calcium and vitamin D can impair bone formation and maintenance
• Physical Activity: Sedentary lifestyles contribute to bone loss while weight-bearing exercise helps maintain bone density.
• Medications and Health Conditions: Certain medications (e. g., glucocorticoids) and health conditions (e. g., rheuma­toid arthritis) can increase osteoporosis risk.

Diagnosis

Accurate diagnosis is crucial for effective management. The cut­ting-edge diagnostic tools to detect fractures and osteoporosis with advanced technology include (► Fig. 1).

• Bone Density Testing: Dual-energy X-ray absorptiometry (DXA) scans measure bone mineral density and are used for diagnosis. Bone densitometry is a reliable method to know the prognosis of osteoporotic conditions. It is conventional to use either of the methods to calculate and diagnose the osteo­porotic condition which is T-Score or Z-Score. T-Score is where standard deviations are compared with a young healthy individual's mean bone density [4]. Z-Score is calculated by comparing standard deviations with mean bone mineral density of individuals of identical age, gender and size [8]. World Health Organization suggested T Score or Z Score value - 1.0 to - 2.5 as low mineral density indicating osteopenia and below - 2.5 indicates porous bone that may tend to fracture, that is, osteoporosis [9, 10].
• Fracture Risk Assessment: FRAX (Fracture Risk Assessment Tool) calculates the ten-year risk of hip and major osteoporot­ic fractures. For the detection of fractures suggested technol­ogy of use is Dual Energy X-ray Absorptiometry. Another technique to know bone mass is high-resolution computed tomography. Ultrasound can predict the fracture by diagnos­ing the bone firmness [9]. A bone biopsy is another method to determine the occurrence of osteoporosis [10].
• Change in Biomarkers: Serum osteocalcin and bone-specific alkaline phosphatase serve as indicators of bone formation, whereas urinary type I collagen C-telopeptide and urinary pyridinoline and deoxypyridinoline serve as indicators of bone resorption. Alterations in these biomarkers are linked to rapid bone loss. Strontium absorption tests determine calcium absorption through the intestine [8, 9].
• Clinical Evaluation: A comprehensive assessment of medical history and risk factors helps identify those at risk [11].

Prevention
Preventing osteoporosis is essential, and lifestyle modifications can significantly reduce the risk [12-14]:

• Diet: Adequate calcium and vitamin D intake through diet or supplements is crucial.
• Physical Activity: Weight-bearing exercises help maintain bone density and strength.
• Lifestyle Choices: Avoiding smoking and excessive alcohol consumption can reduce osteoporosis risk.
• Medication: In some cases, medication may be prescribed to prevent or treat osteoporosis.

Treatment
Several medications are available for osteoporosis management [15-17]:
Bisphosphonates: Alendronate, risedronate, and others inhibit bone resorption.
Hormone Replacement Therapy (HRT): Estrogen therapy can help maintain bone density in postmenopausal women.
Denosumab: A monoclonal antibody that reduces bone resorption.
Teriparatide and Abaloparatide: Anabolic agents that stimulate bone formation.
Calcitonin: Reduces bone resorption and may be used for pain relief.
Emerging Therapies: Novel treatments are under investiga­tion, including sclerostin inhibitors and romosozumab.

Potassium and Bone Health

Mechanisms of Action
Potassium is an essential mineral known primarily for maintaining electrolyte balance and cardiovascular health. However, emerging evidence suggests that potassium may have a positive impact on bone health through several mechanisms [18].

Potassium's Role in Acid-Base Balance and Bone Buffering
Potassium plays a critical role in maintaining acid-base balance in the body. It acts as an alkaline buffer by neutralizing excess acid, which is produced during metabolic processes. This acid-base bal­ance is intimately connected with bone health [19].
Recent studies have highlighted the following key points:

• Acidosis and Bone Resorption: Acidosis, characterized by elevated blood acidity, has been associated with increased bone resorption. The body releases calcium from bones to neutralize excess acid, potentially leading to reduced bone density [20]. Frassetto et al., found that reducing dietary acid load through increased potassium intake can mitigate bone loss [21].
• Potassium's Alkaline Effect: Potassium-rich foods, such as fruits and vegetables, have an alkalizing effect on the body. Alkaline diets have been linked to a lower risk of osteoporosis. Hannan et al., demonstrated that a diet rich in potassium from fruits and vegetables was associated with a higher bone mineral density (BMD) in older adults [22].

Influence of Potassium on Bone Turnover Markers
Potassium has been shown to influence bone turnover markers, providing insights into its direct impact on bone remodeling.

• Serum Alkaline Phosphatase (ALP): Elevated serum ALP levels are associated with increased bone formation. Dawson-Hughes et al., reported that higher potassium intake was positively associated with lower serum ALP levels, suggesting a potential role in regulating bone formation [23].
• Markers of Bone Resorption: Potassium's alkaline properties may also affect markers of bone resorption. Macdonald et al., illustrated that increased fruit and vegetable consumption, rich in potassium, was associated with lower urinary excretion of markers of bone resorption [24].

Interaction with Calcium and Vitamin D in Bone Remodeling
Potassium's interaction with calcium and vitamin D is crucial for bone health.
Calcium Absorption: Adequate potassium levels may enhance calcium absorption in the intestines. Lu et al. showed that potassium supplementation improved calcium retention, potentially promoting bone health [25].
Vitamin D Activation: Potassium may also play a role in vitamin D metabolism. Research carried out by Kim et al., suggests that potassium may influence the conversion of vitamin D to its active form, which is essential for calcium absorption and bone remodeling [26].
A simplified representation of the mechanisms of potassium in os­teoporosis is illustrated in ► Fig. 2.

Cellular Mechanisms
The cellular mechanisms underlying osteoporosis involve a delicate balance between bone formation by osteoblasts and bone resorp­tion by osteoclasts. Emerging research suggests that potassium, an essential mineral, plays a significant role in regulating these cel­lular processes in bone tissue.

Effects of Potassium on Osteoblasts and Osteoclasts
Recent studies have demonstrated that potassium levels can mod­ulate the activity of both osteoblasts and osteoclasts, thereby af­fecting bone health. Potassium exerts its effects through potassi­um channels present on the cell membranes of these bone cells [18].

Potassium Channels in Bone Cells
Potassium channels, specifically the inwardly rectifying potassium (Kir) channels and voltage-gated potassium (Kv) channels, have been identified in osteoblasts and osteoclasts. These channels are involved in regulating membrane potential and intracellular calci­um levels, which are crucial for cellular functions [19].
Osteoblasts: High extracellular potassium concentrations have been shown to enhance the differentiation and minerali­zation of osteoblasts. Activation of Kir channels in osteoblasts can lead to membrane hyperpolarization, triggering calcium influx and promoting osteoblast maturation [3].
Osteoclasts: In contrast, increased extracellular potassium levels inhibit osteoclast activity. High potassium concentra­tions can hyperpolarize osteoclasts, reducing their resorptive capacity. This effect is mediated through voltage-gated potassium channels, which influence calcium signaling in osteoclasts [16].

The Role of Potassium in Collagen Synthesis
Collagen is a major component of the bone matrix and is essential for bone strength. Potassium has been linked to collagen synthesis in osteoblasts. Research suggests that optimal potassium levels are necessary for collagen production, contributing to bone quality and integrity [16, 18].

Epidemiological Evidence

Epidemiological studies have provided supportive evidence for the role of potassium in osteoporosis prevention [16]. Li et al., report­ed that higher dietary potassium intake was associated with in­creased bone mineral density (BMD) in postmenopausal women [27]. In another study Larsson et al., showed that potassium-rich diets were associated with a lower risk of osteoporotic fractures in elderly men [28].

Population Studies
Population studies play a crucial role in understanding the relation­ships between dietary factors and bone health. correlations Between Dietary Potassium Intake and Bone Min­eral Density (BMD) Several population-based studies have inves­tigated the association between dietary potassium intake and BMD:

• NHANESIIIStudy: The National Health and Nutrition Examina­tion Survey III found that higher dietary potassium intake was positively associated with BMD in older adults [29]. Increased potassium intake was linked to higher spine and hip BMD, indicating a potential protective effect on bone density.
• The Framingham Osteoporosis Study: Research from this longitudinal cohort study revealed that higher dietary potassium intake was associated with greater hip BMD in older men and women [30]. These findings suggest a potential role for potassium in preserving bone health with age.

Longitudinal Studies on Potassium-Rich Diets and Fracture Risk
Population-based longitudinal studies have explored the relation­ship between potassium-rich diets and fracture risk:

• The Nurses' Health Study: This prospective cohort study found that postmenopausal women with higher potassium intake had a lower risk of hip fractures [31]. The protective effect of potassium was particularly evident in women who consumed diets rich in fruits and vegetables.
• The Osteoporotic Fractures in Men (MrOS) Study: In this study of older men, those with higher dietary potassium intake had a reduced risk of hip fractures [32] The results support the notion that potassium-rich diets can contribute to fracture prevention in both genders.

Impact of Potassium on Bone Health Across Different Age Groups
Understanding the effects of potassium on bone health across var­ious age groups is essential:
Adolescents and Young Adults: A cross-sectional study conducted by Whiting et al., indicated that higher dietary potassium intake was associated with greater bone mass in adolescents. This suggests that potassium-rich diets during youth may contribute to optimal peak bone mass [33].
Elderly Populations: Research from Harding et al., demonstrat­ed that higher potassium intake was associated with reduced risk of hip fractures in older women. These findings under-
score the importance of potassium in maintaining bone health in the elderly [34].

Clinical Trials
Potassium Supplementation and Bone Health Outcomes Clinical trials have examined the impact of potassium supplemen­tation on bone health outcomes, with promising results. A rand­omized controlled trial carried by Dawson-Hughes et al., investi­gated the effects of potassium bicarbonate supplementation on bone mineral density (BMD) in postmenopausal women. The study found that potassium supplementation led to significant improve­ments in BMD at the lumbar spine [29]. Another clinical trial con­ducted by Orchard et al., explored the effects of potassium citrate supplementation in individuals with osteopenia. The results indi­cated that potassium citrate supplementation was associated with reduced bone resorption and improved bone microarchitecture [35]. A randomized controlled trial conducted by Nasri et al., inves­tigated the effects of potassium supplementation on bone health in postmenopausal women. The study found that daily potassium supplementation led to improved bone mineral density (BMD) at the lumbar spine and hip over a one-year period. This suggests that potassium supplementation may have a positive impact on bone density [36].

Potassium-Rich Diets and Bone Density Changes Clinical trials have assessed the relationship between potassi­um-rich diets and changes in bone density. A study carried by Wu et al., examined the dietary potassium intake of elderly women and its association with changes in BMD over time. The research sug­gested that higher dietary potassium intake was linked to slower BMD decline, supporting the potential benefits of potassium-rich diets in preserving bone density [37]. In a prospective cohort study reported Macdonald et al., researchers assessed the relationship between dietary potassium intake and bone health. The study in­cluded a large sample of postmenopausal women and found a pos­itive association between higher dietary potassium intake and in­creased BMD at the hip and lumbar spine. These findings suggest that potassium-rich diets may support bone density maintenance [38].

Combination Therapy with Potassium, Calcium, and Vitamin D
Clinical trials have explored combination therapies involving po­tassium, calcium, and vitamin D for optimizing bone health. A clin­ical trial reported by Saadi et al. investigated the effects of a com­bination therapy involving calcium, vitamin D, and potassium cit­rate in postmenopausal women. The study demonstrated that this combination therapy had a positive impact on BMD and reduced the risk of fractures [39]. A multicenter randomized trial conduct­ed by Weaver et al. investigated the effects of combination thera­py with potassium, calcium, and vitamin D on bone health in older adults. The trial demonstrated that participants receiving the com­bination therapy exhibited greater improvements in BMD com­pared to those receiving calcium and vitamin D alone. This high­lights the potential synergistic effects of potassium when combined with other bone-boosting nutrients [40].

The findings from these clinical trials have significant therapeu­tic implications for bone health. Potassium supplementation, par­ticularly in the form of potassium citrate or potassium bicarbonate, may offer a non-pharmacological approach to enhance bone min­eral density in postmenopausal women and individuals with osteo­penia. Encouraging potassium-rich diets may be a simple and ac­cessible strategy for preserving bone density in aging populations. Combination therapies involving potassium, calcium, and vitamin D may have synergistic effects on bone health, reducing the risk of fractures and improving bone microarchitecture.

Dietary Guidelines

Diet plays a crucial role in maintaining bone health and overall well-being. In addition to calcium and vitamin D, potassium is an essential nutrient that has garnered attention for its potential role in preventing osteoporosis and maintaining overall health. This ar­ticle explores dietary guidelines related to potassium intake, po­tassium-rich foods, and the importance of balancing potassium and sodium intake, supported by recent evidence [41].

Recommendations for Potassium Intake in Osteoporosis Prevention
The recommended daily intake of potassium varies by age, sex, and individual health status. However, there are general guidelines pro­vided by health organizations, such as the World Health Organiza­tion (WHO) and the U.S. Department of Agriculture (USDA). These guidelines typically recommend a daily intake of around 4700 mil­ligrams (mg) of potassium for adults [41-43].
Recent evidence has shown that maintaining adequate potas­sium intake can be beneficial for bone health and may contribute to osteoporosis prevention. A study carried by Li et al., found that higher dietary potassium intake was associated with increased bone mineral density (BMD) in postmenopausal women, suggesting that meeting recommended potassium levels may support bone health [27].

Potassium-Rich Foods and Their Role in Bone Health
Consuming potassium-rich foods is an effective way to meet daily potassium requirements and support bone health. Key potassi­um-rich foods include [43,44]:

• Fruits: Bananas, oranges, and avocados are rich sources of potassium. These fruits not only provide essential potassium but also contain other nutrients, such as vitamin C and folate, which contribute to overall bone health.
• Vegetables: Spinach, sweet potatoes, and tomatoes are exam­ples of vegetables high in potassium. They are also packed with vitamins and minerals like vitamin K, which plays a crucial role in bone metabolism.
• Legumes: Beans, lentils, and peas are excellent sources of potassium and provide protein and dietary fiber, which are beneficial for bone health.
• Dairy Products: Dairy items like yogurt and milk contain potas­sium along with calcium, which is vital for maintaining strong bones.

Balancing Potassium and Sodium Intake for Overall Health
Maintaining a proper balance between potassium and sodium (salt) intake is essential for overall health, as both minerals have signifi­cant impacts on heart health and blood pressure regulation. High sodium intake is associated with hypertension, which can increase the risk of heart disease and stroke. Recent studies emphasize the importance of reducing sodium intake and increasing potassium intake to mitigate these risks [45].
A potassium-rich diet can help counteract the negative effects of excess sodium by promoting healthy blood pressure levels. In fact, the Dietary Approaches to Stop Hypertension (DASH) diet, which is high in potassium-rich foods and low in sodium, has been shown to reduce blood pressure and improve overall cardiovascu­lar health [46].

Potassium Supplementation

Potassium is an essential mineral that plays a crucial role in various bodily functions, including maintaining proper nerve and muscle function, regulating heart rhythm, and balancing fluid levels. Sup­plementation with potassium may be necessary in certain situa­tions, particularly for at-risk populations and older adults.

Potassium Supplements for At-Risk Populations

• Hypokalemia Risk: Potassium supplementation is often recom­mended for individuals at risk of hypokalemia, which is a con­dition characterized by low potassium levels in the blood. At-risk populations may include people with kidney disease, certain gastrointestinal disorders (e. g., chronic diarrhea), and those taking specific medications such as diuretics, which can lead to potassium loss [47].
• Recommended Dosage: The appropriate dosage of potassium supplements varies depending on individual needs and medi­cal conditions. Typically, healthcare providers prescribe potas­sium supplements in the form of tablets or capsules, with dosages ranging from 20 mEq to 100 mEq per day. However, the dosage should be determined by a healthcare professional after considering the patient's specific circumstances [48, 49].
• Forms of Potassium Supplements: Common forms of potassium supplements include potassium chloride, potassium citrate, and potassium gluconate. The choice of supplement depends on factors like the patient's tolerance, the presence of under­lying conditions, and the potential for drug interactions [49, 50].

Considerations for Supplementation in Older Adults

• Age-Related Changes: Older adults may be at an increased risk of potassium deficiency due to age-related changes in kidney function and reduced dietary intake. Therefore, they may ben­efit from potassium supplementation to maintain healthy potassium levels [50].
• Caution with Medications: Older adults are more likely to be taking medications that can interfere with potassium levels, such as diuretics or certain blood pressure medications. Healthcare providers should carefully consider the interaction between these drugs and potassium supplements to avoid adverse effects [51].
• Individualized Assessment: Supplementation in older adults should be individualized and based on their specific health sta­tus, dietary habits, and medication use. Regular monitoring of potassium levels is essential to prevent both deficiency and excess [52, 53].

Monitoring Potassium Levels and Potential Side Effects

• Regular Blood Tests: People who are prescribed potassium sup­plements should undergo regular blood tests to monitor their potassium levels. This is crucial to ensure that supplementa­tion is effective but not leading to hyperkalemia (excess potas­sium in the blood) [51,52].
• Potential Side Effects: Excessive potassium intake can lead to hyperkalemia, which can cause muscle weakness, irregular heart rhythms, and in severe cases, cardiac arrest. Therefore, it is essential to monitor for symptoms of hyperkalemia and adjust the dosage as needed [47, 54].
• Consultation with Healthcare Provider: Anyone considering potassium supplementation, especially those with underlying health conditions, should consult with a healthcare provider who can provide guidance on the appropriate dosage and monitor for any adverse effects [55].

Interdisciplinary Approaches in Management and Prevention of Osteoporosis

Interdisciplinary approaches have gained prominence in managing and preventing osteoporosis as they leverage the expertise of var­ious healthcare professionals to address the multifactorial nature of the condition. The present review delves into three key interdis­ciplinary approaches in osteoporosis prevention:

Collaborative Efforts between Nutritionists, Endocrinologists, and Bone Specialists
Nutrition plays a pivotal role in bone health, and collaborative ef­forts among nutritionists, endocrinologists, and bone specialists can provide comprehensive care for individuals at risk of osteopo­rosis. Nutritionists can assess dietary intake and formulate person­alized nutrition plans to optimize calcium and vitamin D intake, which are critical for bone health. Endocrinologists can identify hormonal imbalances that may contribute to bone loss, such as hormonal deficiencies or excesses, while bone specialists can eval­uate bone density and assess fracture risk [27]. A study reported by Ceglia et al., demonstrated that collaborative care involving nu­tritionists, endocrinologists, and bone specialists resulted in sig­nificant improvements in bone health markers in postmenopausal women [56].

Personalized Nutrition Plans for Osteoporosis Prevention
Personalized nutrition plans tailored to an individual's specific needs and risk factors can be highly effective in osteoporosis prevention. These plans consider factors such as age, gender, dietary preferences, and existing medical conditions. They aim to optimize calcium and vitamin D intake, as well as other nutrients like potas­sium, magnesium, and protein. Additionally, dietary plans may con­sider the avoidance of excessive sodium and caffeine consumption, as they can contribute to bone loss. A meta-analysis carried by Tang et al., concluded that personalized dietary interventions had a pos­itive impact on bone mineral density, particularly in postmenopau­sal women [57].

Addressing the Potassium-Calcium Balance in Dietary Guidelines
Potassium and calcium are vital minerals for bone health, and main­taining an appropriate balance between them is crucial. High so­dium intake, which is common in many Western diets, can lead to excessive calcium excretion in the urine and increase the risk of os­teoporosis. Interdisciplinary teams can work together to develop dietary guidelines that emphasize potassium-rich foods (e. g., fruits and vegetables) and recommend reducing sodium intake to im­prove the potassium-calcium balance. A study conducted by Tuck­er et al., 1999 found that a higher dietary potassium-calcium ratio was associated with a lower risk of osteoporosis-related fractures in older adults [30].

Limitations of Current Research

Variability in Study Methodologies and Populations
Numerous studies examining the association between potassium intake and bone health have employed different methodologies, including cross-sectional studies, cohort studies, and randomized controlled trials (RCTs). These studies often have varying method­ologies for assessing potassium intake and bone health outcomes. For example, a meta-analysis performed by Lanham-New et al. found significant heterogeneity among studies investigating the association between dietary potassium intake and bone mineral density, highlighting the variability in methodologies and popula­tions [58]. Variability in study designs and methodologies can lead to inconsistent findings and make it difficult to draw definitive con­clusions about the relationship between potassium intake and bone health [59].

The Need for Randomized Controlled Trials (RCTs)
While there is evidence from observational studies suggesting a positive association between higher potassium intake and better bone health, the gold standard for establishing causation is RCTs. RCTs involve randomly assigning individuals to different levels of potassium intake and observing the impact on bone health out­comes. RCTs help control for confounding variables and provide stronger evidence for causation [60]. Identifying the optimal range of potassium intake that promotes bone health without causing harm requires more research, including RCTs and long-term stud­ies. A meta-analysis reported by Lambert et al. concluded that both low and high potassium intakes may be associated with a higher risk of osteoporosis, emphasizing the need for further research to determine optimal levels [61]. The scarcity of RCTs specifically de­signed to assess the effects of potassium supplementation on bone health limits our ability to make definitive conclusions regarding the causal relationship.

Identifying Optimal Potassium Levels for Bone Health
There is a lack of consensus regarding the optimal level of potassi­um intake for promoting bone health. Some studies suggest that higher potassium intake is associated with improved bone density and reduced risk of fractures, while others find no significant asso­ciation or even potential adverse effects at very high potassium lev­els. Optimal potassium levels may vary depending on an individu­al's overall diet and other factors [62]. The lack of a clear consen­sus on the optimal potassium intake for bone health makes it challenging to provide specific dietary recommendations.

Potential Risks

Monitoring potassium levels in individuals with renal issues and bal­ancing potassium intake with medications are important consid­erations in healthcare to prevent potential risks associated with po­tassium imbalances.

Monitoring Potassium Levels in Individuals with Renal Issues
Potassium is an essential mineral that plays a critical role in various bodily functions, including nerve function, muscle contractions, and maintaining heart rhythm. However, the kidneys are respon­sible for regulating potassium levels in the body by excreting ex­cess potassium through urine. In individuals with renal (kidney) is­sues, such as chronic kidney disease (CKD), the kidneys may not function properly, leading to a potential risk of high potassium lev­els in the blood (hyperkalemia). Hyperkalemia can have serious consequences, including cardiac arrhythmias and muscle weakness, which can be life-threatening if not properly managed [63, 64].

Balancing Potassium Intake with Medications
Some medications can affect potassium levels in the body. For ex­ample, certain medications, like potassium-sparing diuretics (e. g., spironolactone), can increase potassium levels, while others, like certain diuretics (e. g., furosemide), can decrease potassium lev­els. It is crucial to balance dietary potassium intake with medica­tions to prevent either hyperkalemia (high potassium) or hypo­kalemia (low potassium). Imbalances in potassium levels can lead to adverse health effects. High potassium levels can cause heart rhythm disturbances, and low potassium levels can result in mus­cle weakness and irregular heartbeat [65, 66].

Future Research Areas

Potassium is an essential mineral in the human body, primarily known for its role in maintaining electrolyte balance and regulat­ing blood pressure. However, emerging evidence suggests that po­tassium may also play a significant role in bone health by influenc­ing bone microarchitecture, including bone density and structure. Conducting longitudinal studies to investigate the association be­tween dietary potassium intake and bone microarchitecture. These studies could include advanced imaging techniques like high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess bone quality. Examining the potential mechanisms through which potassium affects bone microarchitecture. This might involve in vitro studies using bone cell cultures to understand the cellular processes involved [67].
Genetic factors can play a crucial role in determining an individ­ual's potassium metabolism and, by extension, their bone health. Identifying specific genes and genetic variations associated with potassium metabolism and bone health can provide valuable in­sights into personalized medicine and interventions. Genome-wide association studies (GWAS) to identify genetic variants associated with potassium metabolism and bone health outcomes such as bone mineral density and fracture risk. Investigating gene-environ­ment interactions to understand how genetic factors and dietary potassium intake interact to influence bone health [68].
To understand how potassium influences bone health at the cel­lular level, mechanistic studies are essential. These studies can pro­vide insights into the signaling pathways and cellular processes in­volved in potassium's impact on bone cells. Conducting in vitro studies using bone cell cultures to investigate how potassium in­fluences osteoblast (bone-forming cell) and osteoclast (bone-re- sorbing cell) activity. This could involve exploring potassium's ef­fects on cell proliferation, differentiation, and mineralization [69].

Marketed Products of Potassium

Potassium supplements are available in many salt forms like Potas­sium gluconate, Potassium Chloride, Potassium Citrate, Potassium Asporotate, Potassium Iodide, Potassium Magnesium Citrate, Po­tassium Magnesium Aspartate, Potassium Bicarbonate in various brand names for different indications like Nephrotic stones, hypo­kalemia, Hypertension, Arrhythmia, Thallium toxicity, Hyperthy­roidism, Sporotrichosis [70]. Potassium bicarbonate cannot be given orally since it releases carbon dioxide that could impart a del­eterious effect on gastric mucosa [71].
Some Potassium Supplements Products that are Available in the Market
Although the branded products of potassium listed (► Table 1) below are just a few examples of potassium supplements, they are also a prescription medication that is available in tablet, capsule, powder form. Low blood potassium levels are treated or prevent­ed using this medication. Only use prescription drugs as directed by a healthcare professional.

Other Products
Twinlab Potassium Caps, Country Life Target-Mins Potassium, Solgar Potassium Tablets, Nature's Way Potassium Chelate, Bluebon­net Nutrition Chelated Potassium, Douglas Laboratories Potassium 99 mg Chelated, Life Extension Potassium Caps, Solaray Potassium Asporotate, Pure Encapsulations Potassium Magnesium Citrate, Doctor's Best High Absorption Magnesium & Potassium, GNC Po­tassium Magnesium Aspartate, Now Foods Potassium Citrate Pow­der, Himalayan Organics Potassium Citrate Tablets, Jarrows Potas­sium Citrate Tablets, Source Naturals Potassium Iodide.

Adverse Reactions, Drug Interactions and Contraindications to Potassium Supplements

To guarantee the safety and efficacy of the medication, potassium contraindications or potential drug interactions should be careful­ly reviewed and assessed prior to usage. Potassium is contraindi­cated in hyperkalemia and it tends to interact with Angioten­sin-Converting Enzyme (ACE) Inhibitors, Angiotensin Receptor Blockers (ARBs) [72] and Potassium-Sparing Diuretics (Triamterene, Amiloride, Spironolactone) causing hyperkalemia [73], gastroin­testinal adverse drug reactions [74], esophageal obstruction [75], Perforation of Small Bowel [76], ulcer, and stenosis [77].
The National Academies of Sciences describes the Dietary Ref­erence Intakes (DRIs) for potassium as guidelines established by the National Academies of Sciences, Engineering and Medicine to help people maintain a healthy diet and avoid nutrient deficiencies. The article specifically focuses on the potential toxicity of potassi­um, providing recommendations for safe intake levels and poten­tial adverse effects of consuming too much potassium. Although not consistently, high, acute potassium intakes have been linked to symptoms of neuromuscular dysfunction such as weakness, pa­ralysis, nausea, vomiting and diarrhea [78].
Potassium overdose is also related to morbidity as mentioned in one of the case studies by Guillermo et al., where a deliberate in­gestion of 100 extended release potassium chloride pills, 50 mg of clonazepam, and an unknown quantity of ethanol by a woman (42 years of age) resulted in hyperlactatemia, metabolic acidosis, and sinus tachycardia within two hours. No particular procedures were required after the patient originally received therapy with activat­ed charcoal and gastric lavage. She did, however, need to have a transcutaneous pacemaker implanted. Her medical history led to the suspicion of a pharmacobezoar, which was treated with an en­doscopy to eliminate 99 pills of potassium that had developed con­cretions [79].
Afshar et al., demonstrated that the BALB/c fetal mice devel­oped their eyes with substantial abnormalities as a result of long­term potassium benzoate ingestion. The detected consequences included ocular malformations and structural abnormalities, sug­gesting that potassium benzoate may be teratogenic. The level of potassium benzoate exposure and the severity of the anomalies were associated [80].

Safe Dose of Potassium

It seems that adding around 2500 mg/day (64 mmol/day) of potas­sium in regular meal for a brief period is not risky for individuals who are generally in good health [78].
A study conducted Goyal et al., in 2012 revealed that individu­als who suffer from Acute Myocardial Infarction displayed a lower incidence of mortality if their potassium levels in serum lie within range of 3.5 mEq/l and < 4.5 mEq/l conversely to potassium levels that were higher or lower. Therefore, it is plausible to deduce that healthy serum potassium values may fall within the range of 3.5 mmol/l and 5.0 mmol/l. Levels that fall beyond this range could potentially result in death due to various complications [81].
A reference daily intake (RDI) for potassium is set by the Food and Drug Administration (FDA). RDI refers to ‘the quantity of a nuSingh W, Kushwaha P. Potassium: A Frontier in... Florm Metab Res | © 2024. Thieme. All rights reserved.
► Table 1 An overview on marketed products of potassium.
En­
try Brand Manufacturer Marketed by Category Dose Dosage
form Formulation
technology Reference
1. Klor-Con® (USP) Upsher Smith Laboratories. LLC Upsher Smith Laboratories. LLC Potassium Chloride 600 mg, 750 mg ERTab Wax Matrix
Tablet RxList [85]
2. Klor-Con®M
10/15/20 (USP) Upsher Smith Laboratories. LLC Upsher Smith Laboratories. LLC Potassium Chloride 750 mg, 1125 mg, 1500 mg ERTab ME Dailymed [86]
3. KCI Cure (I.P.) Pharma Cure Laboratories/ Curetech Formulations (P)
Ltd Hargun Biotech Potassium Chloride 1500mg in 10 mL Liquid
Injection Not Specified Pharmacure Laboratories [87]
4. K-TAB (USP) AbbVie LTD AbbVie Inc. Potassium Chloride 600 mg, 750 mg, 1500 mg ERTab Film sealed tablet Food and Drug Administration [88]
5. Slow-K (USP) Novartis Pharmaceutical Corporation Novartis Pharmaceutical Corporation Potassium Chloride 600 mg ERTab Wax Matrix RxList [89]
6. Sando-K Alturix Limited Sandoz Potassium Chloride (Ph.Eur.), Potassium Bicarbonate (USP) 600 mg + 400 mg ERTab Not Specified Medicines [90]
7. Micro-K ExtenCaps (USP) KV Pharmaceutical Ther Rx Corporation Potassium Chloride 600 mg, 750 mg ER- HCCap ME RxList [91]
8. K-Dur(USP) Key Pharmaceuticals Inc. Key Pharmaceuticals Inc. Potassium Chloride 750 mg, 1500 mg ERTab ME Drugs [92]
9. Urikind-K Oral Solution (USP) Cris Pharma (India) Ltd Mankind Pharmaceuticals Potassium Citrate 1100 mg Oral Solution Not Specified 1 mg [93]
10. Urocit-K Mission Pharmaceutical Allmed Labs Potassium Citrate 1080 mg ERTab Wax Matrix
Tablets Urocit-K [94]
11. Bone Up Jarrow Formulas Jarrow Formulas Potassium Citrate 99 mg Capsule Not Specified Jarrow [95]
12. Klotrix Bristol-Myers Squibb
Company Bristol-Myers Squibb Company Potassium Chloride 750 mg ERTab Film-Coated
Wax-Matrix Drugs [96]
Tablet

ER Tab: Extended Release Tablets; ER-HG Cap: Extended Release Hard Gelatin Capsules; ME: Microencapsulation.

trient thought to be enough to fulfill the needs of most healthy people on a daily basis'. According to the FDA, potassium RDI is 4700 milligrams per day indicated to individuals over the age of 14. However, certain populations may require different amounts, such as pregnant or lactating women [82].
As per National Institute of Health Adequate intake (AI) of po­tassium recommended for 14 to 18 years of age is 3000 mg (male) and 2300 mg (female), 19 to 50 years of age and above 3400 (male) 2600 mg (female). For pregnant ladies of age 14 to 18 years AI of potassium recommended is 2600 mg and 19 to 50 years is 2900 mg whereas for lactating mothers recommended AI for the age be­tween 14 to 18 years is 2500 mg and for 19 to 50 years is 2800 mg. This recommended AI is not applicable for patients with any renal condition [83].
Around 90 % of the potassium consumed, which amounts to 60-100 mEq, is eliminated through urine, 10 % of the body's waste is passed in the stool, and some is lost through perspiration. De­spite this, uncertainty exists regarding the bioavailability of potas­sium from dietary sources, and its impact on health outcomes re­mains largely unknown [84].

Summary and Conclusion

In the ever-evolving landscape of bone health research, potassium emerges as a frontier with immense potential to reshape our un­derstanding of osteoporosis. The journey of exploring the role of this essential mineral in bone microarchitecture, deciphering ge­netic factors influencing potassium metabolism, and unraveling mechanistic insights into its effects on bone cells has opened a world of possibilities. As we navigate the complexities of osteopo­rosis, the evidence amassed from studies linking potassium intake to improved bone mineral density and reduced fracture risk in post­menopausal women and older adults cannot be overlooked. The tantalizing prospect of potassium as a modifiable dietary factor brings hope for preventive strategies and personalized interven­tions. Furthermore, genetics adds a layer of complexity and intrigue to the potassium-bone health equation. Genetic factors influence not only our potassium metabolism but also our predisposition to bone-related disorders. By delving into the genetic determinants of potassium and bone health, we may unearth the keys to person­alized osteoporosis management and treatment.
Mechanistic studies at the cellular level have unveiled glimpses of how potassium interacts with bone cells, from osteoblasts to os­teoclasts. These investigations shed light on the intricate molecu­lar pathways that underlie the effects of potassium on bone remod­eling. Such insights hold promise for the development of targeted therapies that can harness potassium's potential to strengthen bones.
In conclusion, the exploration of potassium's role in osteoporo­sis represents an exciting frontier in bone health research. It beck­ons us to venture further, to probe deeper, and to seek answers that may ultimately transform the way we approach osteoporosis prevention and treatment. With continued dedication and scien­tific rigor, potassium may well become a cornerstone in our efforts to fortify the foundations of bone health for generations to come.

96 References

Adejuyigbe B, Kallini J, Chiou D et al. Osteoporosis: molecular pathology, diagnostics, and therapeutics. Int J Mol Sci 2023; 24: 14583

1. Svedbom A, Hernlund E, Ivergàrd M et al. Osteoporosis in the European Union: a compendium of country-specific reports. Archiv Osteoporos 2013; 8: 1-218.
2. Eastell R, O’Neill TW, Hofbauer LC et al. Postmenopausal osteoporosis. Nat Rev Dis Primers 2016; 2: 1-6
3. Khadilkar AV, Mandlik RM. Epidemiology and treatment of osteoporosis in women: an Indian perspective. Int J Womens Health 2015; 7: 841-850
4. Clynes MA, Harvey NC, Curtis EM et al. The epidemiology of osteoporosis. Br Med Bull 2020; 133: 105-117
5. Wright NC, Looker AC, Saag KG et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 2014; 29: 2520-2526
6. Nuti R, Brandi ML, Checchia G et al. Guidelines for the management of osteoporosis and fragility fractures. Intern Emerg Med 2019; 14: 85-102
7. Kranioti EF, Bonicelli A, García-Donas JG. Bone-mineral density: clinical significance, methods of quantification and forensic applications. Res Rep Forensic Med Sci 2019; 25: 9-21
8. Chitra V. Diagnosis, screening and treatment of osteoporosis-a review. Biomed Pharmacol J 2021; 14: 567-575
9. Sheu A, Diamond T. Diagnostic tests: bone mineral density: testing for osteoporosis. Austr Prescriber 2016; 39: 35-39
10. Fuggle NR, Curtis EM, Ward KA et al. Fracture prediction, imaging and screening in osteoporosis. Nat Rev Endocrinol 2019; 15: 535-547
11. Khosla S, Cauley JA, Compston J et al. Addressing the crisis in the treatment of osteoporosis: a path forward. J Bone Miner Res 2018; 33: 1393-1394
12. Ralston SH, Uitterlinden AG. Genetics of osteoporosis. Endocr Rev 2019; 40: 575-599
13. Kadam NS, Chiplonkar SA, Khadilkar AV et al. Prevalence of osteoporosis in apparently healthy adults above 40 years of age in Pune City, India. Indian J Endocrinol Metab 2018; 22: 67-73
14. Tu KN, Lie JD, Wan CK et al. Osteoporosis: a review of treatment options. Pharm Therap 2018; 43: 92-104
15. Sozen T, Oziçik L, Bagaran NÇ. An overview and management of osteoporosis. Eur J Rheumatol 2017; 4: 46-56
16. Cosman F, Crittenden DB, Adachi JD et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Eng J Med 2017; 376: 1432-1443
17. Sakhaee K, Maalouf NM, Abrams SA et al. Effects of potassium alkali and calcium supplementation on bone turnover in postmenopausal women. J Clin Endocrinol Metab 2005; 90: 3528-3533
18. Starke A, Corsenca A, Kohler T et al. Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality. Clin J Am Soc Nephrol 2012; 7: 1461-1472
19. Gregory NS, Kumar R, Stein EM et al. Potassium citrate decreases bone resorption in postmenopausal women with osteopenia: a randomized, double-blind clinical trial. Endocr Pract 2015; 21: 1380-1386
20. Lambert H, Frassetto L, Moore JB et al. The effect of supplementation with alkaline potassium salts on bone metabolism: a meta-analysis. Osteoporos Int 2015; 26: 1311-1318
21. Hannan MT, Tucker KL, Dawson-Hughes B et al. Effect of dietary protein on bone loss in elderly men and women: the Framingham Osteoporosis Study. J Bone Miner Res 2000; 15: 2504-2512
22. Dawson-Hughes B, Harris SS, Palermo NJ et al. Potassium bicarbonate supplementation lowers bone turnover and calcium excretion in older men and women: a randomized dose-finding trial. J Bone Miner Res 2015;30: 2103-2111
23. Tylavsky FA, Holliday K, Danish R et al. Fruit and vegetable intakes are an independent predictor of bone size in early pubertal children. Am J Clin Nutr 2004; 79: 311-317
24. Praditsap O, Sawasdee N, Pungsrinont T et al. Genetic heterogeneity of kidney stone disease in northeastern Thai patients. Genom Genet 2022; 15: 1-5
25. Han H, Segal AM, Seifter JL, Dwyer JT. Nutritional management of kidney stones (nephrolithiasis). Clin Nutr Res 2015; 4: 137-152
26. Lim SY, Joo-Hak Kim MD. Nutrient intake risk factors of osteoporosis in postmenopausal women. Asia Pac J Clin Nutr 2008; 17: 270
27. Laurent MR, Gielen E, Orwoll E et al. Osteoporosis in men: what is similar and what is different? In: Marcus and Feldman’s Osteoporosis. AmsterdaM: Elsevier; 2020: 589-632
28. Gregory NS, Kumar R, Stein EM et al. Potassium citrate decreases bone resorption in postmenopausal women with osteopenia: a randomized, double-blind clinical trial. Endocr Pract 2015; 21: 1380-1386
29. Tucker KL, Hannan MT, Chen H et al. Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. Am J Clin Nutr 1999; 69: 727-736
30. Ryder KM, Shorr RI, Bush AJ et al. Magnesium intake from food and supplements is associated with bone mineral density in healthy older white subjects. J Am Geriatr Soc 2005; 53: 1875-1880
31. Seth A, Mossavar-Rahmani Y, Kamensky V et al. Potassium intake and risk of stroke in women with hypertension and nonhypertension in the Women’s Health Initiative. Stroke 2014; 45: 2874-2880
32. Whiting SJ, Boyle JL, Thompson A et al. Dietary protein, phosphorus and potassium are beneficial to bone mineral density in adult men consuming adequate dietary calcium. J Am Coll Nutr 2002; 21: 402-409
33. Granchi D, Caudarella R, Ripamonti C et al. Potassium citrate supplementation decreases the biochemical markers of bone loss in a group of osteopenic women: the results of a randomized, double­blind, placebo-controlled pilot study. Nutrients 2018; 10: 1293
34. Granchi D, Torreggiani E, Massa A et al. Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss. PLoS One 2017; 12: e0181230
35. Humalda JK, Yeung SM, Geleijnse JM et al. Effects of potassium or sodium supplementation on mineral homeostasis: a controlled dietary intervention study. J Clin Endocrinol Metab 2020; 105: e3246-e3256
36. Hu D, Cheng L, Jiang W. Fruit and vegetable consumption and the risk of postmenopausal osteoporosis: a meta-analysis of observational studies. Food Funct 2018; 9: 2607-2616
37. Wilson-Barnes SL, Lanham-New SA, Lambert H. Modifiable risk factors for bone health & fragility fractures. Best Pract Res Clin Rheumatol 2022; 36: 101758
38. Papadimitropoulos E, Wells G, Shea B et al. VIII: meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women. Endocr Rev 2002; 23: 560-569
39. Martiniakova M, Babikova M, Mondockova V et al. The role of macronutrients, micronutrients and flavonoid polyphenols in the prevention and treatment of osteoporosis. Nutrients 2022; 14: 523
40. Guideline WH. Potassium intake for adults and children. World Health Organization (WHO); Geneva, Switzerland. 2012: 1-52
41. US Department of Agriculture, US Department of Health and Human Services. Dietary Guidelines for Americans 2020; 2020-2025
42. Frassetto LA, Goas A, Gannon R et al. Potassium. Adv Nutr 2023; 14: 1237
43. Orchard TS, Larson JC, Alghothani N et al. Magnesium intake, bone mineral density, and fractures: results from the Women’s Health Initiative Observational Study. Am J Clin Nutr 2014; 99: 926-933
44. Sacks FM, Svetkey LP, Vollmer WM et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. N Eng J Med 2001; 344: 3-10
45. Saneei P, Salehi-Abargouei A, Esmaillzadeh A. Serum potassium levels and risk of stroke: a dose-response meta-analysis of prospective studies. J Am Coll Nutr 2013; 32: 240-249
46. Kardalas E, Paschou SA, Anagnostis P et al. Hypokalemia: a clinical update. Endocr Connect 2018; 7: R135-R146
47. Weaver CM. Potassium and health. Adv Nutr 2013; 4: 368S-377S
48. Palmer BF. Potassium supplements and salt substitutes containing potassium in CKD. Am J Kidney Dis 2019; 74: 259-262
49. Geleijnse JM, Kok FJ, Grobbee DE. Blood pressure response to changes in sodium and potassium intake: a metaregression analysis of randomised trials. J Hum Hyperten 2003; 17: 471-480
50. Cupisti A, Kovesdy CP, D’Alessandro C et al. Dietary approach to recurrent or chronic hyperkalaemia in patients with decreased kidney function. Nutrients 2018; 10: 261
51. Mount DB, Zandi-Nejad K. Disorders of potassium balance. In Brenner & Rector's Kidney Brenner BM, Rector FC (eds), 8th ed. Saunders Elsevier;Philedelphia, Chap: 15
52. Appel LJ, Moore TJ, Obarzanek E et al. A clinical trial of the effects of dietary patterns on blood pressure. N Eng J Med. 1997; 336: 1117-1124
53. Knochel JP. Hypokalemia Adv Inten Med 1984; 30: 317-335
54. Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Eng J Med 2015; 372: 274-275
55. Ceglia L, Harris SS, Abrams SA et al. A randomized study of the effects of vitamin D supplementation on muscle function. J Clin Endocrinol Metab 2013; 98: 1611-1618
56. Tang BMP, Eslick GD, Nowson C et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2015; 385: 1011-1018
57. Wang L, Yin L, Cheng X et al. The association of calcium intake with osteoporotic vertebral fractures in a large Chinese cohort. Aging (Albany NY) 2020; 12: 5500
58. Dawson-Hughes B. Acid-base balance of the diet - implications for bone and muscle. Eur J Clin Nutr 2020; 74: 7-13
59. Dawson-Hughes B, Harris SS. Calcium intake influences the association of protein intake with rates of bone loss in elderly men and women. Am J Clin Nutr 2002; 75: 773-779
60. Dominguez LJ, Veronese N, Ciriminna S et al. Association between serum magnesium and fractures: a systematic review and meta­analysis of observational studies. Nutrients 2023; 15: 1304
61. Ascherio A, Rimm EB, Hernán MA et al. Intake of potassium, magnesium, calcium, and fiber and risk of stroke among US men. Circulation 1998; 98: 1198-1204
62. Levey AS, Becker C, Inker LA. Glomerular filtration rate and albuminuria for detection and staging of acute and chronic kidney disease in adults: a systematic review. J Am Med Assoc 2015; 313: 837-846
63. Palmer BF, Clegg DJ. Electrolyte and acid-base disturbances in patients with diabetes mellitus. N Eng J Med 2015; 373: 548-559
64. McMurray JJ, Adamopoulos S, Anker SD et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European society of cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012; 33: 1787-1847
65. Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized aldactone evaluation study investigators. N Engl J Med 1999;341: 709-717
66. Macdonald HM, Black AJ, Aucott L et al. Effect of potassium citrate supplementation or increased fruit and vegetable intake on bone metabolism in healthy postmenopausal women: a randomized controlled trial. Am J Clin Nutr 2008; 88: 465-474
67. Li GH, Robinson-Cohen C, Sahni S et al. Association of genetic variants related to serum calcium levels with reduced bone mineral density. J Clin Endocrinol Metab 2020; 105: e328-e336
68. Zanello LP, Norman A. 1a,25 (OH) 2 vitamin D3 actions on ion channels in osteoblasts. Steroids 2006; 71: 291-217
69. Sur M, Mohiuddin SS. Potassium. InStatPearls [Internet] 2022 May 11. StatPearls Publ https://www.ncbi.nlm.nih.gov
70. Arnett TR. Acidosis, hypoxia and bone. Archiv Biochem Biophys 2010; 503:103-109
71. Raebel MA, McClure DL, Simon SR et al. Laboratory monitoring of potassium and creatinine in ambulatory patients receiving angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Pharmacoepidemiol Drug Safety 2007; 16: 55-64
72. Green DM, Ropper AH, Kronmal RA et al. Serum potassium level and dietary potassium intake as risk factors for stroke. Neurology 2002; 59: 314-320
73. Pietro DA, Davidson L. Evaluation of patient’s preference of two potassium chloride supplements: Slow-K and K-Dur. Clin Therap 1990; 12: 431-435
74. Pemberton J. Oesophageal obstruction and ulceration caused by oral potassium therapy. Br Heart J 1970; 32: 267-268
75. Farquharson-Roberts MA, Giddings AE, Nunn AJ. Perforation of small bowel due to slow release potassium chloride (slow-K). Br Med J 1975; 3: 206
76. Howie AD, Strachan RW. Slow release potassium chloride treatment. Br Med J 1975; 2: 176
77. National Academies of Sciences, Engineering, and Medicine. Dietary reference intakes for sodium and potassium; 2019. https://www.nap. nationalacademies.org
78. Guillermo PT, Carlos PH, Ivonne BA et al. Extended release potassium salts overdose and endoscopic removal of a pharmacobezoar: a case report. Toxicol Rep 2014; 1: 209-213
79. Afshar M, Moallem SA, Khayatzadeh J et al. Teratogenic effects of long term consumption of potassium benzoate on eye development in BALB/c fetal mice. Iran J Basic Med Sci 2013; 16: 593
80. Goyal A, Spertus JA, Gosch K et al. Serum potassium levels anmortality in acute myocardial infarction. J Am Med Assoc 2012; 307: 157-164
81. Hoque M, Emon K, Malo PC et al. Comprehensive guide to vitamin and mineral sources with their requirements. Indiana J Agric Life Sci 2023; 3:23-31
82. National Institutes of Health (NIH). Potassium - fact sheet for health professionals. 2021. https://ods.od.nih.gov/factsheets/Potassium- HealthProfessional/
83. Stone MS, Martyn L, Weaver CM. Potassium intake, bioavailability, hypertension and glucose control. Nutrients 2016; 8: 444
84. RxList. KLOR-CON. Retrieved June 21,2023 from https://www.rxlist.com/klor-con-drug.htm#description
85. Dailymed. KLOR-CON M- potassium chloride tablet, extended release. Retrieved June 21,2023 from https://dailymed.nlm.nih.gov/dailymed/ fda/fdaDrugXsl.cfm?setid = b89910f6-4ff5-4a62-8269- 696f7c10e4f6&type = display
86. Pharmacurelaboratories. Potassium Chloride Injection. Retrieved June 21,2023 from https://www.pharmacurelabs.com/potassium-chloride- injection-3307667.html
87. Food and Drug Administration. K-TAB®. Retrieved June 21,2023 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018279s034lbl.pdf
88. RxList. SLOW-K. Retrieved June 21,2023 from https://www.rxlist.com/slow-k-drug.htm#description
89. Medicines. Sando-K. Retrieved June 21,2023 from https://www.medicines.org.uk/emc/product/959/smpc#gref
90. RxList. Micro-K. Retrieved June 21,2023 from https://www.rxlist.com/micro-k-drug.htm
91. Drugs. K-Dur Dosage. Retrieved June 21,2023 from https://www.drugs.com/dosage/k-dur.html
92. 1 mg. Urikind -K Solution. Retrieved June 21,2023 from https://www.1mg.com/drugs/urikind-k-solution-147808?wpsrc = Google + Organic + Search
93. Urocit-K. Urocit-K 15 mEq Potassium citrate extended release tablet. Retrieved June 21,2023 from https://www.urocit-k.com/
94. Jarrow. BoneUp®. Retrieved June 21,2023 from https://jarrow.com/products/boneup-capsules
95. Drugs. Klotrix Prescribing Information. Retrieved June 21,2023 from https://www.drugs.com/pro/klotrix.html

Vitamin D Life – Bone - Health category contains

• Overviews: Osteoporosis,  Fractures,  Rickets  Dental   Hair
• 15 articles are in both Bone and Magnesium categories
• 28 articles are in both Bone and Vitamin K2 categories
• 17 articles are in both Bone and Sports categories
• 8 articles are in both Bone and Meta-analysis categories
• 24 articles are in both Fractures and Meta-analysis categories
• Healthy bones need: Calcium, Vitamin D, Magnesium, Silicon, Vitamin K, and Boron – 2012
• Vitamin D Life pages with BONE MINERAL DENSITY or BMD in title 25 pages as of Feb 2023
• Hearing loss is associated with soft bones in ear
  • Perhaps prevented and treated by Vitamin D

Vitamin D Life – Overview Osteoporosis and vitamin D contains

• FACT: Bones need Calcium (this has been known for a very long time)
• FACT: Vitamin D improves Calcium bioavailability (3X ?)
• FACT: Should not take > 750 mg of Calcium if taking lots of vitamin D (Calcium becomes too bio-available)
• FACT: Adding vitamin D via Sun, UV, or supplements increased vitamin D in the blood
• FACT: Vitamin D supplements are very low cost
• FACT: Many trials, studies. reviews, and meta-analysis agree: adding vitamin D reduces osteoporosis
• FACT: Toxic level of vitamin D is about 4X higher than the amount needed to reduce osteoporosis
• FACT: Co-factors help build bones.
• FACT: Vitamin D Receptor can restrict Vitamin D from getting to many tissues, such as bones
• It appears that to TREAT Osteoporosis:
•        Calcium OR vitamin D is ok
•        Calcium + vitamin D is good
•        Calcium + vitamin D + other co-factors is great
•        Low-cost Vitamin D Receptor activators sometimes may be helpful
• CONCLUSION: To PREVENT many diseases, including Osteoporosis, as well as TREAT Osteoporosis
• Category Osteoporosis has 215 items
• Category Bone Health has 307 items

Note: Osteoporosis causes bones to become fragile and prone to fracture
  Osteoarthritis is a disease where damage occurs to the joints at the end of the bones

Vitamin D Life – Osteoporosis category contains

• 215 items in category - see also Overview Osteoporosis and vitamin D
• Overview Fractures and vitamin D
• Bone - Health 307 items
• Vitamin D Life pages with BONE MINERAL DENSITY or BMD in title 29+ pages
• Search Vitamin D Life for OSTEOPENIA 1740 items as of July 2020
• 13 articles are in both Osteroporosis and Vitamin D Receptor categories
• 9 articles are in both Osteroporosis and Meta-analysis categories
• 20X increase in vitamin D sold and 36 percent decrease in osteoporosis business in Australia – Nov 2013

5+ Vitamin D Life pages have POTASSIUM in the title

This list is automatically updated

Vitamin D Life – Calcium hazards and bioavailability contains

• All items with Calcium in Vitamin D Life 220 items
• Calcium from food or supplements associated with more deaths (US Cohort of 31,000 people) – April 2019
• More Calcium absorbed with more vitamin D – 6.7% more with 4000 IU – RCT March 2014
• Decrease Calcium and Increase Magnesium when increasing vitamin D
• Calcium supplements proven to NOT reduce fractures, but are proven to INCREASE heart problems – July 2015
• More than 1.4 grams of Calcium increased male death rate by 1.4 X – Sept 2018
• 10,000 IU of Vitamin D is too much if you also take Calcium supplements – RCT Sept 2018
• Calcium Essential to Limit Osteoporosis but Avoid Excess, Say Europeans - Nov 2017
• Hypercalcemia can result from excess Vitamin D (if not reduce Ca or increase water) Oct 2016
• Must balance co-factors when increasing vitamin D 500 Ca, 500 Mg - which has the following concept graph

• More than 800 mg of Calcium increases Cardiovascular events by 85 %– Nov 2011

Chart of recent decrease in Potassium from crops - published 2020

https://doi.org/10.1021/acs.jafc.0c05139