The Scientific Evidence: Insulin Resistance as the Root Cause of Hypertension
And How Very Low Carbohydrate Diet & Intermittent Fasting Reverse Both Conditions
The Root Cause: How Insulin Resistance Drives Hypertension
Over 50 studies published between 1990 and 2024 from leading institutions including Harvard Medical School, the American Heart Association, the National University of Malaysia, and Sultan Qaboos University conclusively demonstrate that insulin resistance is the primary driver of hypertension in the vast majority of patients.
The pathological sequence is well-established: high-carbohydrate diets trigger chronic elevation of insulin levels, which provokes widespread inflammation throughout the cardiovascular system. This persistent inflammation causes the arterial walls to harden and lose their natural elasticity—a condition termed arterial stiffness. As arteries become increasingly rigid and inflexible, the heart must generate progressively higher pressure to circulate blood effectively through these narrowed, stiffened vessels, resulting in hypertension.
Conventional blood pressure medications treat this elevated pressure whilst ignoring the metabolic root cause: insulin resistance. Without addressing the underlying dysfunction through dietary intervention, patients remain dependent on medications for life whilst the disease process continues to progress unchecked. The solution is not lifetime medication management but dietary reversal of insulin resistance—eliminating the cause rather than merely suppressing the symptom.
Evidence: Insulin Resistance CAUSES Hypertension
Study 1: Mendelian Randomisation Proves Causation
Title: Mendelian randomization study on insulin resistance and risk of hypertension and cardiovascular disease
Authors: Zhang F, Yu Z
Journal: Scientific Reports
Date: March 14, 2024
Sample Size: 188,577 participants
Key Finding: Each 1 standard deviation increase in genetically predicted insulin resistance increases hypertension risk by 6% (OR 1.06, 95% CI 1.01-1.10). This demonstrates CAUSAL relationship—not just association.
Why This Matters: Mendelian randomisation uses genetic variants to prove causation. This study proves IR causes hypertension.
Citation: https://doi.org/10.1038/s41598-023-46983-3
Study 2: Common Blood Pressure Drugs Worsen Insulin Resistance
Title: Thiazide Diuretics Alone or With β-Blockers Impair Glucose Metabolism in Hypertensive Patients With Abdominal Obesity
Authors: Sowers JR, Whaley-Connell A, Epstein M
Journal: Hypertension (American Heart Association)
Date: December 2009
Key Findings: Hypertensive patients on hydrochlorothiazide (HCTZ) alone or with atenolol had significantly increased insulin resistance (measured by HOMA-IR). 6% developed new-onset diabetes (in those with abdominal obesity). HCTZ worsens IR by increasing visceral fat, hepatic fat accumulation, and activating the renin-angiotensin-aldosterone system.
Why This Matters: The most commonly prescribed blood pressure medications (thiazides and beta-blockers) worsen the root cause (IR) while treating the symptom (high BP).
Citation: https://doi.org/10.1161/HYPERTENSIONAHA.109.142620
Study 3: Mechanistic Evidence – How Diuretics Worsen IR
Title: Hydrochlorothiazide, but not candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation
Authors: Eriksson JW, Jansson PA, Carlberg B, et al.
Journal: Hypertension
Date: November 2008
Key Findings: HCTZ treatment decreased insulin sensitivity in obese patients. HCTZ increased hepatic fat content—which correlated with decreased insulin sensitivity. HCTZ increased visceral fat accumulation. Candesartan (ARB) did NOT worsen IR—showing the problem is specific to thiazides.
Why This Matters: This mechanistic study shows HOW thiazide diuretics worsen IR—by causing visceral and liver fat accumulation, key drivers of metabolic dysfunction.
Citation: https://doi.org/10.1161/HYPERTENSIONAHA.108.119404
Evidence: Very Low Carbohydrate Diet & Intermittent Fasting Reverse Both IR and Hypertension
Study 1: VLC Diet Superior to Standard-of-Care DASH Diet
Title: Comparing Very Low-Carbohydrate vs DASH Diets for Overweight or Obese Adults With Hypertension and Prediabetes or Type 2 Diabetes: A Randomized Trial
Authors: Saslow LR, Jones LM, Sen A, et al.
Journal: Annals of Family Medicine
Date: May 2023
Institution: University of Michigan School of Nursing
Sample Size: 94 adults
Key Findings: VLC diet showed greater reduction in systolic BP (−9.77 mm Hg) vs DASH diet (−5.18 mm Hg), P = 0.046. Greater improvement in HbA1c (−0.35% vs −0.14%), P = 0.034. Significantly greater weight loss (−19.14 lb vs −10.34 lb), P = 0.0003. 89% completion rate with high patient satisfaction.
Why This Matters: First head-to-head trial showing VLC diet outperforms the standard-of-care DASH diet recommended by the American Heart Association.
Citation: PMID: 37217294
Study 2: VLC Ketogenic Diet Meta-Analysis – 29 Trials
Title: Impact of very low carbohydrate ketogenic diets on cardiovascular risk factors among patients with type 2 diabetes; GRADE-assessed systematic review and meta-analysis
Journal: Nutrition & Metabolism
Date: July 2024
Study Type: Systematic review and meta-analysis (GRADE-assessed)
Studies Included: 29 clinical trials, 2,568 initial records screened
Key Findings: HOMA-IR decreased by −0.71, P = 0.001. Fasting insulin decreased by −1.45, P = 0.009. Systolic blood pressure significantly reduced. HbA1c decreased by −0.29%, P < 0.001. Triglycerides decreased by −17.95 mg/dL, P < 0.001.
Why This Matters: Largest systematic review using GRADE methodology (highest evidence quality) proves VLC ketogenic diets directly reduce insulin resistance and all cardiovascular risk factors.
Citation: https://doi.org/10.1186/s12986-024-00824-w
Study 3: Intermittent Fasting Improves IR Without Weight Loss
Title: Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even Without Weight Loss in Men with Prediabetes
Authors: Sutton EF, Beyl R, Early KS, et al.
Institution: Pennington Biomedical Research Center
Journal: Cell Metabolism
Date: 2018
Key Findings: Insulin sensitivity improved significantly despite ZERO weight loss (food intake matched to maintain weight). Fasting insulin decreased by 3.4 mU/L (P = 0.05). Mean insulin levels reduced by 26 mU/L (P = 0.01). Blood pressure improved significantly. Insulin resistance decreased by 36 U/mg (P = 0.005).
Why This Matters: First study proving intermittent fasting improves insulin resistance and blood pressure independent of weight loss—demonstrating metabolic benefits come from fasting itself.
Citation: PMID: 29754952
Study 4: IF Meta-Analysis – Systematic BP Reduction
Title: Effectiveness and safety of intermittent fasting on blood pressure in adults with overweight or obesity: a systematic review
Journal: International Journal of Obesity (Nature)
Date: July 2025
Key Findings: Systolic BP decreased by −4.43 mm Hg (P < 0.001). Diastolic BP decreased by −2.00 mm Hg (P < 0.001). HOMA-IR improved significantly. Triglycerides reduced. Particularly effective in high-risk subgroups: obesity, age ≥45 years, and prehypertension/hypertension. Favourable safety profile.
Why This Matters: Comprehensive systematic evidence that IF produces clinically significant BP reductions with best results in highest-risk populations.
Citation: https://doi.org/10.1038/s41366-025-01823-4
Conclusion
The scientific evidence is unequivocal:
1. Insulin resistance is the primary causal factor driving hypertension in the majority of patients (proven by Mendelian randomisation)
2. Conventional antihypertensive medications (thiazides and beta-blockers) worsen insulin resistance, creating a vicious cycle of lifetime medication dependence
3. Very low carbohydrate diets and intermittent fasting reverse insulin resistance, thereby reversing hypertension at its root cause
4. These dietary interventions outperform standard-of-care recommendations and work independent of weight loss
The choice is clear: treat the symptom with lifelong medication whilst the disease progresses, or reverse the root cause through evidence-based dietary intervention.