Orthomolecular interventions
Orthomolecular interventions are nutrients and actions that promote health by supporting the body’s specific biochemical needs. These interventions can include specific diets, foods, nutrients, and lifestyle changes.
Beneficial diets
Diets that have been shown to prevent or decrease hypertension
DASH Diet (Dietary Approaches to Stop Hypertension)
- High in fruits, vegetables, whole grains, low-fat dairy; moderate in nuts and legumes; low in red meat, sugar, and saturated fat
- Shown in a clinical trial to reduce systolic blood pressure by 5.5 mm Hg and diastolic blood pressure by 3.0 mm Hg more than a control diet (BioLINCC: Dietary Approaches to Stop Hypertension (DASH), n.d.).
Mediterranean Diet
- Emphasizes olive oil, fruits, vegetables, legumes, nuts, whole grains, fish; moderate red wine; low red meat and processed foods
- A systematic review and meta-analysis showed a positive and significant association between the Mediterranean Diet and blood pressure in adults (Nissensohn et al., 2016)
Whole-Food, Anti-Inflammatory Diets
- Minimally processed foods, high in antioxidants and fibre, moderate healthy fats
- A meta-analysis of 18 randomized control trials showed that adhering to anti-inflammatory diets led to an average systolic blood pressure reduction of −3.99 mm Hg, and diastolic blood pressure reduction of −1.81 mm Hg (Jiang et al., 2025).
Vitamin B1 (thiamine)
Thiamine is a water-soluble vitamin. Thiamine deficiency is implicated in hypertension.
Key ways thiamine deficiency promotes hypertension include:
- decreasing mitochondrial energy production, which negatively impacts the ability of cells to function normally – low energy in endothelial cells causes cellular dysfunction and promotes increased vascular contraction (Wilson et al., 2022)
- damaging cells by simultaneously causing oxidative stress (due to mitochondrial dysfunction) and impairing the activity of thiamine-dependent enzymes needed for antioxidant defence – oxidative stress decreases nitric oxide, and increases inflammation and vascular stiffness (Pushpakumar et al., 2014)
- impairing the function of the enzyme pyruvate dehydrogenase, which causes pyruvate to be converted to lactate – leads to lactic acidosis, which lowers cellular pH, damages mitochondria, impairs enzyme activity, and can trigger cell death (Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition, 2017)
- impairing kidney filtration by damaging kidney vascular circulation (Rabbani et al., 2009)
- decreasing prevention of glucose- and insulin-induced proliferation of smooth muscle cells – which in turn, causes increased atherosclerotic plaque formation and reduced blood flow (Ritorto et al., 2025)
“Thiamine deficiency should be considered in all patients with pulmonary hypertension of unknown origin” (Asakura et al., 2013).
Thiamine deficiency, elevated blood-sugar, and hypertension
Elevated blood sugar (hyperglycemia), especially in the context of diabetes, prediabetes, and metabolic syndrome, is known to reduce thiamine levels (Thornalley et al., 2007). The effects of hyperglycemia add to the effects of low thiamine by:
- further impairing mitochondrial energy production (adenosine triphosphate (ATP)
- further increasing production of reactive oxygen species (ROS)
- increasing the production of advanced glycation end products (AGEs) and their corresponding vascular damage
- damaging kidney nephrons and filtering capacity (Rabbani et al., 2009)
Vitamin B6
Actions of vitamin B6 in preventing and addressing hypertension include: (Tsuda & Nishio, 2004):
- regulating homocysteine levels, which prevents homocysteine-induced damage to the blood vessels
- supporting nitric oxide production by helping to lower homocysteine levels
- supporting the synthesis of dopamine, norepinephrine, serotonin, and GABA – these neurotransmitters decrease/modulate sympathetic nervous system function, which decreases blood pressure
- supporting sodium excretion by the kidneys
- reducing free radicals and pro-inflammatory cytokines
- regulating cellular calcium levels – excess calcium in endothelial cells causes vasoconstriction (Vasdev et al., 1999)
Deficiency of vitamin B6 can be identified by:
- the absence of dreams, or the inability to remember dreams
- having disturbing dreams or nightmares
Causes of vitamin B6 deficiencies
- inadequate dietary intake
- medications, including anti-tuberculosis drugs, anti-parkinsonians, nonsteroidal anti-inflammatory drugs, and oral contraceptives, may interfere with vitamin B6 metabolism (Vitamin B6, 2014)
- alcoholism – due to low intake and impaired metabolism of vitamin B6
- long-term diuretic medication therapy (Houston, 2013)
Vitamin C
Actions of vitamin C in preventing and addressing hypertension include:
- increasing the availability and action of nitric oxide by (Mullan et al., 2002) by:
- protecting it from deterioration due to oxidative stress caused by free radicals
- promoting nitric oxide production (via the enzyme nitric oxide synthase)
- preventing oxidation of low-density lipoprotein (LDL), which impedes nitric oxide production
- improving sensitivity of cells to insulin, which can increase the release of nitric oxide
- decreasing arterial stiffness by:
- protecting against free radical damage
- supporting collagen synthesis – which supports healthy elasticity and integrity of the arterial wall (May & Harrison, 2013)
- decreasing arterial inflammation by decreasing pro-inflammatory cytokines (Ellulu et al., 2015)
- decreasing the formation of AGEs (AGEs cause arterial stiffening, oxidative stress, and inflammation) (Rabizadeh et al., 2023)
Vitamin C deficiency
Causes of Vitamin C deficiency include:
- restrictive diets
- diet lacking in sources of vitamin C, especially fresh fruit and vegetables
- digestive tract disorders, e.g. diarrhea, Crohn’s and colitis
- smoking
- alcoholism
- chronic inflammatory conditions
Signs of vitamin C deficiency:
- bleeding or swollen gums
- frequent nosebleeds
- dry hair, split ends
- easy bruising
- slow wound healing
- fatigue
- moodiness
- depression and cognitive impairment (Plevin & Galletly, 2020)
Folate
Key actions of folate in preventing and addressing hypertension include:
- reducing homocysteine via conversion to methionine which:
- reduces endothelial damage and improves vascular tone
- supporting key enzymes involved in nitric oxide synthesis by stabilizing and enhancing the function of endothelial nitric oxide synthase (eNOS) (Li et al., 2015)
- regenerating tetrahydrobiopterin (BH4) (Crabtree et al., 2009)
- reducing free radical production (Mangoni et al., 2002)
- supporting production of the important antioxidant glutathione (Ducker & Rabinowitz, 2017), and maintaining NADPH levels (Fan et al., 2014)
Causes of folate deficiencies
- low dietary intake
- poor absorption
- gastrointestinal issues
- chronic alcoholism
- smoking
- oral contraceptives (Gaby, 2011)
- drug interactions (Folate, 2014)
- genetic variations in folate metabolism, for example variations the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (“Folate”, 2014)
Calcium
Roles of calcium in blood pressure management:
- stabilizes vascular cell membranes (Houston & Harper, 2008)
- stable membranes decrease calcium entry into the cells
- less calcium in cells results in decreased smooth muscle contraction and vasoconstriction
- suppresses production of 1,25-dihydroxyvitamin D, thereby reducing inflow of calcium into the smooth muscle cells of blood vessels (Zemel, 2001; Jayedi et al., 2019)
- promotes sodium excretion by the kidneys (Zemel, 2001)
- decreases the action of renin – which decreases the formation of angiotensin II (Jayedi et al., 2019)
- counters the loss of calcium in the urine that occurs as a result of high salt intake in sensitive individuals (Zemel, 2001)
Getting the right amount of calcium is important for keeping blood pressure healthy, but too little or too much calcium can raise the risk of hypertension.
Key ways calcium DEFICIENCY promotes hypertension include:
- promoting smooth muscle contraction by:
- increasing intracellular calcium influx into vascular smooth muscle (McCarron, 1983)
- increased creation of parathyroid hormone (Jorde et al., 2000) and 1,25-dihydroxyvitamin D (the hormone form of vitamin D) (Audran & Kumar, 1985) which:
- increases renin, angiotensin II and aldosterone – which increase sodium retention and vasoconstriction
- impairs endothelial nitric oxide production
- increasing sympathetic nervous system activity – which elevates vascular tone and heart rate (Linder et al., 2024)
Key ways calcium EXCESS promotes hypertension include:
- increasing calcium influx into vascular smooth muscle cells – which enhances contraction (Nadler & Antonipillai, 1986)
- promoting calcium buildup in vascular cells – which leads to arterial stiffening (Nadler & Antonipillai, 1986)
Dietary calcium intake and hypertension
- Higher dietary calcium consumption of calcium has been correlated with both reduced blood pressure and a lower risk of hypertension (Houston & Harper, 2008).
- Salt-sensitive people are the group most likely to experience blood pressure–lowering benefits from higher dietary calcium intake (Zemel, 2001).
- Studies using dietary sources of calcium showed roughly twice the effect on lowering blood pressure, and with greater consistency, compared to studies using calcium supplements (Zemel, 2001).
How much calcium to reduce blood pressure?
- Meta-analyses of 42 clinical trials found that increasing calcium intake by 1,000 to 2,000 mg per day led to significant reductions in blood pressure (Zemel, 2001).
- A study by Jayedi et al., (2019) showed a 7% lower risk of developing hypertension for each 500 mg increase in daily calcium intake.
Magnesium
Actions of magnesium in preventing and addressing hypertension include:
- promoting vasodilation and blood vessel relaxation (Houston & Harper, 2008)
- reducing the flow of calcium into the heart and arteries by acting as a natural calcium channel blocker (Houston & Harper, 2008)
Magnesium and hypertension
- Several epidemiological studies have shown an inverse relationship between dietary magnesium intake and blood pressure. A meta-analysis by Jee et al. (2002) reported significant, dose-dependent reductions in blood pressure with magnesium supplementation.
- A study by Resnick et al. (1984) found that people with untreated high blood pressure had lower levels of free magnesium inside their cells compared to those with normal blood pressure.
- Clinical trials using high-dose magnesium in patients with eclampsia and glomerulonephritis have demonstrated significant reductions in blood pressure (Jee et al., 2002).
- Kass et al. (2012) reported in their meta-analysis reductions in both systolic and diastolic blood pressure with supplementation of magnesium (Kass et al., 2012).
Magnesium deficiency is common
- Dietary intake of magnesium has declined significantly over the past 100 years putting people at greater risk of deficiency (Kass et al., 2012).
- Up to 30% of a given population may have subclinical serum magnesium deficiency (DiNicolantonio & O’Keefe, 2021).
- Magnesium deficiency is relatively common and often unrecognized in clinical settings, as magnesium is rarely tested (Wallace, 2020).
- Magnesium deficiency is associated with (Dominguez et al., 2021):
- increased inflammation
- increased oxidative stress
Reasons for magnesium deficiencies include:
- increased stress (causes magnesium depletion)
- low dietary protein (needed for magnesium absorption)
- gastrointestinal disorders (e.g. Crohn’s disease, malabsorption syndromes, and prolonged diarrhea)
- high doses of supplemental zinc (competes for absorption)
- certain diuretic medications
- alcoholism
- age – elderly adults tend to have lower dietary intake, absorption, and increased loss of magnesium
Potassium
Actions of potassium in preventing and addressing hypertension include:
- stimulating the kidneys to excrete more sodium – which reduces extracellular fluid volume and lowers blood pressure (Gritter et al., 2019; Preuss, 1997)
- inducing relaxation of vascular smooth muscle by activating potassium channels (Baranowska et al., 2007; Haddy et al., 2006)
- protecting against vascular calcification and stiffness (Xie et al., 2023)
- regulating electrolyte and fluid balance – which helps maintain osmotic balance and blood pressure homeostasis (World Health Organization, 2012)
- limiting blood renin activity (Kanbay et al., 2013)
- protecting endothelial function from the effects of elevated sodium (Smiljanec et al., 2020)
Potassium and hypertension
- Observational studies and clinical trials consistently show that higher potassium levels are linked to lower blood pressure (Houston & Harper, 2008).
- A large meta-analysis by Aburto et al. (2013) of 22 randomized trials found that increased potassium intake reduced systolic blood pressure by ~5.3 mm Hg and diastolic blood pressure by ~3.1 mm Hg in hypertensive adults.
- Increasing potassium intake by 750–1,000 mg a day has been shown to decrease blood pressure by 2–3 mm Hg (Houston & Harper, 2008).
- The effects of potassium on hypertension are greater in hypertensive people verses those without hypertension (Houston & Harper, 2008).
- Increasing potassium intake has been shown to lower blood pressure, even among people who are following a relatively low-sodium diet (Gijsbers et al., 2015).
“Increased potassium intake should be considered as a recommendation for prevention and treatment of hypertension, especially in those who are unable to reduce their intake of sodium” (Whelton et al., 1997).
EPA/DHA/Fish oils
Actions of the essential fatty acids EPA and DHA (fish oils) in preventing and addressing hypertension include:
- supporting nitric oxide (NO) production by:
- upregulating endothelial nitric oxide synthase (eNOS) (Niazi et al., 2017)
- preventing NO breakdown by reducing oxidative stress (via reduced NADPH oxidase activity) (Niazi et al., 2017)`
- promoting healthy arterial structure by:
- reducing infiltration of inflammatory cells and expression of adhesion molecules
- reducing triglycerides and LDL oxidation, resulting in less arterial wall thickening and stiffness
- improving cell membrane composition (changing fluidity and signal transduction), making them more responsive to vasodilators
- decreasing renin-angiotensin-aldosterone system (RAAS) activity
- decreasing blood viscosity by:
- decreasing levels of fibrinogen which contributes to clot formation and plasma viscosity
- inhibiting platelet aggregation by reducing thromboxane A2 (TXA2), and increasing anti-aggregatory prostaglandins (e.g., PGI3)
- enhancing red blood cell flexibility and deformability (which allows them to flow through capillaries with less resistance)
“Eicosapentaenoic acid (EPA or fish oil) lowers abnormal blood lipid levels and decreases blood viscosity. Fish oil, like niacin, raises HDL and reduces risk from heart disease (Braverman, 1992)”.
EPA/DHA/Fish oil and Hypertension
- Daily consumption of EPA and DHA by individuals with systolic hypertension resulted in blood pressure reductions of clinical relevance (Minihane et al., 2016).
- Intake of Omega 3 fatty acids by individuals with chronic kidney disease (CKD) resulted decreased blood pressure levels (Mori et al., 2009).
Coenzyme Q10 (CoQ10)
Actions of CoQ10 in preventing and addressing hypertension include:
- Supporting nitric oxide levels:
- Enhances eNOS activity (endothelial nitric oxide synthase), promoting nitric oxide production.
- Reduces oxidative degradation of nitric oxide, improving its bioavailability (Tiano et al., 2007).
- Supporting mitochondrial energy production:
- Mitochondrial dysfunction is recognized in the pathophysiology of hypertension (Dikalov & Ungvari, 2013).
- CoQ10 plays a central role in the mitochondrial electron transport chain, where it helps drive energy (ATP) production.
- Adequate ATP is necessary for the function of vascular smooth muscle cells and maintaining vascular tone (contraction and relaxation of blood vessels) (Wilson et al., 2023).
- Reducing oxidative stress by:
- acting as an antioxidant, especially in its ubiquinol form – decreasing oxidative damage to lipids, proteins, and DNA (Littarru & Tiano, 2007).
- countering reduced nitric oxide availability and constriction of arterial smooth muscle that results from oxidative stress in the endothelial tissue (Rosenfeldt et al., 2007)
- Decreasing vascular inflammation by:
- suppressing pro-inflammatory cytokines like CRP, IL-6, and TNF-αwhich are associated with endothelial dysfunction and hypertension (Fan et al., 2017) – which leads to improved arterial health and lower blood pressure (Maladkar, 2016).
- Enhancing the elasticity of large arteries (Vrentzos et al., 2024)
CoQ10 and hypertension
- Several studies have demonstrated the effectiveness of CoQ10 in reducing hypertension (Burke et al., 2001).
- A study by Rosenfeldt et al. (2007) found that Coenzyme Q10 may reduce systolic blood pressure by as much as 17 mm Hg and diastolic blood pressure by up to 10 mm Hg in hypertensive patients, without significant side effects.
- CoQ10 was found to lower blood pressure in people with type 2 diabetes (Hodgson et al., 2002).
CoQ10 deficiency and hypertension
- All tissues and organs of the body contain CoQ10, with the highest concentration being in the heart (Rosenfeldt et al., 2007).
- Aging and cardiovascular disease reduce levels of CoQ10 (Rosenfeldt et al., 2007).
- CoQ10 deficiency has been identified in individuals with hypertension (Rosenfeldt et al., 2007).
