HIGH INSULIN = FRAGILE BONES, Cancer & Faster Aging - PhD Cooper & MD Berry
In this hard-hitting interview, Dr. Ken Berry and PhD researcher Dr. Isabella Cooper (@I_mitochondria) blow the lid off why so many women fracture easily despite “normal or great” bone density scans. Dr. Cooper opens with her groundbreaking paper on hyperinsulinemia-osteofragility — how excess insulin quietly destroys bone quality while scans look fine.
They then unpack Insulin-Compensated Euglycemia (ICE): millions walk around with perfect glucose and HbA1c while sky-high insulin nukes their mitochondria and shuts down ketosis. Dr. Cooper explains her Homeodynamics paper, proving chronic hyperinsulinemia plus zero ketones wrecks autophagy, mitophagy, and drives accelerated ageing.
Her landmark KetoSAge trials deliver the receipts: healthy, lean, long-term keto women were forced onto official “healthy eating guidelines.” Insulin, IGF-1, inflammation, and liver enzymes exploded while protective SHBG crashed — clear evidence that mainstream carb-heavy advice may fast-track ageing and cancer signaling. The damage reversed the moment they returned to ketosis.
The conversation closes with cancer as a metabolic-endocrine-bioenergetics disease, glucose + glutamine addiction, and a remarkable stage IV breast cancer near-complete remission case using therapeutic ketosis and metabolic support instead of toxic chemo alone. Eye-opening, controversial, and full of hope for anyone tired of “your labs are normal” gaslighting.
::: spoiler summerizer
Bone density and bone quality
- Bone mineral density is an incomplete proxy for bone health, because bone quality determines fracture risk more directly.
- Normal or high DEXA results can give false reassurance when bone is mineralized but brittle.
- Fragility fracture risk in this model is not only porous osteoporosis; it can also involve dense, fossilized, low-ductility bone.
- Strong bone needs torsion strength and ductility, not just more mineral mass.
Bones, metabolism, and mental health
- Bone is biologically active tissue connected with insulin sensitivity, weight regulation, brain health, and pancreatic function.
- Poor bone quality connects with anxiety, stress, depression, gestational diabetes risk, and fetal development in this model.
- Bone health affects the developing baby through maternal metabolic health, with downstream relevance to anxiety, depression, and IQ.
- Bones are not passive scaffolding; they are part of whole-body metabolic regulation.
Hyperinsulinemia and fracture risk
- Too much insulin is the core metabolic problem, and hyperinsulinemia is the preferred term over insulin resistance.
- Type 2 diabetes can involve normal or high bone density while fracture risk remains elevated.
- A matched cohort of type 2 diabetes patients linked insulin therapy with a 38% higher fracture risk than nonuse.
- A male type 2 diabetes cohort over age 65 linked higher bone mineral density with higher fragility fracture risk.
Glucose-centered medicine and ICE
- Normal glucose can hide excessive insulin demand when insulin keeps glucose in range.
- ICE means normal-looking glucose maintained by too much insulin, while ketosis is suppressed.
- Glucose tests, HbA1c, and HOMA-IR are useful but insufficient for detecting personal hyperinsulinemia.
- Evening ketones under 0.5 mmol/L across repeated days can signal that insulin is high enough to suppress ketogenesis.
Glucose lowering trial and mortality
- The Action to Control Cardiovascular Risk in Diabetes trial found that glucose lowering through more intensive drug-driven insulin exposure increased mortality.
- The danger was the method used to lower HbA1c, not a healthy lower HbA1c achieved through diet and lifestyle.
- Better glucose regulation should come from lowering insulin demand, with diet as the largest driver.
- Sleep, nighttime light exposure, sympathetic stress, and some medications can also affect glucose and insulin dynamics.
Aging, insulin, IGF-1, and ketones
- Modern aging includes longer life through drugs but earlier chronic disease and longer morbidity.
- Dementia, cardiovascular disease, stroke, and cancer are too-much-insulin conditions in this model and occur earlier with chronic hyperinsulinemia.
- Cross-species whole-life animal data connects longevity and healthspan with low insulin and low IGF-1, not zero insulin or zero IGF-1.
- The goal is a homeodynamic range with the least insulin and IGF-1 needed for maximal function.
Redox biology and cellular repair
- Chronic high insulin demand consumes and impairs endogenous antioxidant systems.
- Ketogenesis above 0.5 mmol/L signals insulin is low enough to allow fatty-acid burning and ketone production.
- Low insulin with ketones supports antioxidant production, autophagy, mitophagy, mitochondrial biogenesis, and cellular cleanup.
- Chronic suppression of ketogenesis shifts cells away from repair and toward aging, senescence, and poorer tissue function.
Protein, stomach acid, and osteopenia
- Ketosis may improve protein recycling, but damaged proteins such as glycated proteins still need disposal.
- Osteopenia or osteoporosis can coexist with real nutrient deficits, so high-quality whole food protein remains important.
- Whole-formed protein gives digestive and intestinal signaling that hydrolyzed protein does not fully duplicate.
- Hyperinsulinemia can damage stomach acid production, impair digestion, and worsen micronutrient absorption.
Osteoporosis drugs and acid suppression
- Bisphosphonates can irritate the stomach lining.
- Acid blockers are often paired with bisphosphonates for reflux symptoms.
- Acid suppression can worsen the underlying digestion and nutrient-absorption problem.
- Symptom control without metabolic repair can compound the bone-health problem.
KetoSAge findings
- In the KetoSAge work, lean healthy long-term keto-adapted women had ketosis deliberately suppressed by a guideline-style diet.
- Suppressed ketosis increased insulin, IGF-1, inflammatory markers, liver markers, glucose, and respiratory quotient.
- Sex hormone binding globulin fell during ketosis suppression and returned toward baseline when nutritional ketosis resumed.
- Testosterone, estradiol, progesterone, and related reproductive hormone patterns did not show harmful disruption in that cohort.
Thyroid, HOMA-IR, and RQ
- Low T3 in a ketogenic phenotype is not automatically hypothyroidism.
- Low T3 can reflect efficient fat and ketone metabolism when HOMA-IR, ketones, and clinical context are healthy.
- Low T3 with suppressed ketogenesis can reflect insulin-driven thyroid stress and impaired iodine handling.
- Respiratory quotient can show whether fasted resting metabolism is mainly using fat, carbohydrate, or protein.
Cancer metabolism and therapeutic ketosis
- Ketosis is not a stand-alone cancer cure, and standard cancer care still has a place.
- Therapeutic ketosis can improve chemotherapy efficacy and reduce toxicity burden in this model.
- Cancer is defined here by chronic overproliferation plus loss of apoptosis.
- Metabolic health and low insulin demand can lower the drive toward overproliferation and impaired cell cleanup.
Insulin, mitochondria, and cancer signaling
- Excess glucose and insulin raise mitochondrial oxidative stress and inflammatory signaling.
- HIF-1 alpha, NF-kappa-beta, inflammasomes, and TNF-alpha push cells toward glycolysis and division.
- Overactive HIF-1 alpha and mitochondrial stress shut down autophagy, mitophagy, and mitochondrial biogenesis.
- Replicating damaged cellular machinery compounds dysfunction.
Glucose, glutamine, and dairy in cancer
- Glucose feeds much of the cancer energy demand, while insulin gives proliferation and anti-apoptosis signals.
- Glutamine is life-essential, but glutaminolysis in this model sits downstream of glucose and insulin pressure.
- People with cancer are advised here to avoid milk, yogurt, kefir, and cheese.
- Dairy is portrayed as hyperanabolic because whey, casein, IGF-1, lactose, and glutamine together activate growth pathways.
Serum insulin testing and prevention
- Serum insulin should be checked with glucose, HbA1c, thyroid, and bone-related bloodwork.
- Elevated insulin can occur before overt diabetes, prediabetes, cancer, dementia, cardiovascular disease, and bone fragility.
- UK access to insulin testing is limited unless diabetes or prediabetes is already recognized.
- Wider insulin testing and cheaper point-of-care insulin assays would support prevention.
Medical education and chronic disease care
- Endocrine education remains glucose-centered in this account.
- Professional education often centers new drugs for hyperglycemia or reflux and leaves root pathology unresolved.
- Acute medication has a valid role, but chronic disease care should improve the condition and reduce medication burden over time.
- A patient whose chronic condition worsens while medications multiply may need a different clinical approach.
References
- [00:00] Rethinking Fragility Fractures in Type 2 Diabetes: The Link between Hyperinsulinaemia and Osteofragilitas — https://doi.org/10.3390/biomedicines9091165
- [00:04] Insulin use and Excess Fracture Risk in Patients with Type 2 Diabetes: A Propensity-Matched cohort analysis — https://doi.org/10.1038/s41598-017-03748-z
- [00:05] Fracture risk in diabetic elderly men: the MrOS study — https://doi.org/10.1007/s00125-014-3289-6
- [00:10] Effects of Intensive Glucose Lowering in Type 2 Diabetes — https://doi.org/10.1056/NEJMoa0802743
- [00:15] Bio-Hacking Better Health—Leveraging Metabolic Biochemistry to Maximise Healthspan — https://doi.org/10.3390/antiox12091749
- [00:27] How and Why We Age — https://www.worldcat.org/oclc/1035597432
- [00:32] Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females — https://doi.org/10.3390/ijms242115621
- [00:32] Ketosis Suppression and Ageing (KetoSAge): The Effect of Suppressing Ketosis on GKI and Liver Biomarkers in Healthy Females — https://doi.org/10.3390/LIVERS5030041
- [00:32] Ketosis suppression and ageing (KetoSAge): the effect of suppressing ketosis on SHBG and sex hormone profiles in healthy premenopausal women, and its implications for cancer risk and therapy — https://doi.org/10.3389/fnut.2025.1731915
- [00:34] Ketosis Suppression and Ageing (KetoSAge) Part 2: The Effect of Suppressing Ketosis on Biomarkers Associated with Ageing, HOMA-IR, Leptin, Osteocalcin, and GLP-1, in Healthy Females — https://doi.org/10.3390/biomedicines12071553
:::
They then unpack Insulin-Compensated Euglycemia (ICE): millions walk around with perfect glucose and HbA1c while sky-high insulin nukes their mitochondria and shuts down ketosis. Dr. Cooper explains her Homeodynamics paper, proving chronic hyperinsulinemia plus zero ketones wrecks autophagy, mitophagy, and drives accelerated ageing.
Her landmark KetoSAge trials deliver the receipts: healthy, lean, long-term keto women were forced onto official “healthy eating guidelines.” Insulin, IGF-1, inflammation, and liver enzymes exploded while protective SHBG crashed — clear evidence that mainstream carb-heavy advice may fast-track ageing and cancer signaling. The damage reversed the moment they returned to ketosis.
The conversation closes with cancer as a metabolic-endocrine-bioenergetics disease, glucose + glutamine addiction, and a remarkable stage IV breast cancer near-complete remission case using therapeutic ketosis and metabolic support instead of toxic chemo alone. Eye-opening, controversial, and full of hope for anyone tired of “your labs are normal” gaslighting.
::: spoiler summerizer
Bone density and bone quality
- Bone mineral density is an incomplete proxy for bone health, because bone quality determines fracture risk more directly.
- Normal or high DEXA results can give false reassurance when bone is mineralized but brittle.
- Fragility fracture risk in this model is not only porous osteoporosis; it can also involve dense, fossilized, low-ductility bone.
- Strong bone needs torsion strength and ductility, not just more mineral mass.
Bones, metabolism, and mental health
- Bone is biologically active tissue connected with insulin sensitivity, weight regulation, brain health, and pancreatic function.
- Poor bone quality connects with anxiety, stress, depression, gestational diabetes risk, and fetal development in this model.
- Bone health affects the developing baby through maternal metabolic health, with downstream relevance to anxiety, depression, and IQ.
- Bones are not passive scaffolding; they are part of whole-body metabolic regulation.
Hyperinsulinemia and fracture risk
- Too much insulin is the core metabolic problem, and hyperinsulinemia is the preferred term over insulin resistance.
- Type 2 diabetes can involve normal or high bone density while fracture risk remains elevated.
- A matched cohort of type 2 diabetes patients linked insulin therapy with a 38% higher fracture risk than nonuse.
- A male type 2 diabetes cohort over age 65 linked higher bone mineral density with higher fragility fracture risk.
Glucose-centered medicine and ICE
- Normal glucose can hide excessive insulin demand when insulin keeps glucose in range.
- ICE means normal-looking glucose maintained by too much insulin, while ketosis is suppressed.
- Glucose tests, HbA1c, and HOMA-IR are useful but insufficient for detecting personal hyperinsulinemia.
- Evening ketones under 0.5 mmol/L across repeated days can signal that insulin is high enough to suppress ketogenesis.
Glucose lowering trial and mortality
- The Action to Control Cardiovascular Risk in Diabetes trial found that glucose lowering through more intensive drug-driven insulin exposure increased mortality.
- The danger was the method used to lower HbA1c, not a healthy lower HbA1c achieved through diet and lifestyle.
- Better glucose regulation should come from lowering insulin demand, with diet as the largest driver.
- Sleep, nighttime light exposure, sympathetic stress, and some medications can also affect glucose and insulin dynamics.
Aging, insulin, IGF-1, and ketones
- Modern aging includes longer life through drugs but earlier chronic disease and longer morbidity.
- Dementia, cardiovascular disease, stroke, and cancer are too-much-insulin conditions in this model and occur earlier with chronic hyperinsulinemia.
- Cross-species whole-life animal data connects longevity and healthspan with low insulin and low IGF-1, not zero insulin or zero IGF-1.
- The goal is a homeodynamic range with the least insulin and IGF-1 needed for maximal function.
Redox biology and cellular repair
- Chronic high insulin demand consumes and impairs endogenous antioxidant systems.
- Ketogenesis above 0.5 mmol/L signals insulin is low enough to allow fatty-acid burning and ketone production.
- Low insulin with ketones supports antioxidant production, autophagy, mitophagy, mitochondrial biogenesis, and cellular cleanup.
- Chronic suppression of ketogenesis shifts cells away from repair and toward aging, senescence, and poorer tissue function.
Protein, stomach acid, and osteopenia
- Ketosis may improve protein recycling, but damaged proteins such as glycated proteins still need disposal.
- Osteopenia or osteoporosis can coexist with real nutrient deficits, so high-quality whole food protein remains important.
- Whole-formed protein gives digestive and intestinal signaling that hydrolyzed protein does not fully duplicate.
- Hyperinsulinemia can damage stomach acid production, impair digestion, and worsen micronutrient absorption.
Osteoporosis drugs and acid suppression
- Bisphosphonates can irritate the stomach lining.
- Acid blockers are often paired with bisphosphonates for reflux symptoms.
- Acid suppression can worsen the underlying digestion and nutrient-absorption problem.
- Symptom control without metabolic repair can compound the bone-health problem.
KetoSAge findings
- In the KetoSAge work, lean healthy long-term keto-adapted women had ketosis deliberately suppressed by a guideline-style diet.
- Suppressed ketosis increased insulin, IGF-1, inflammatory markers, liver markers, glucose, and respiratory quotient.
- Sex hormone binding globulin fell during ketosis suppression and returned toward baseline when nutritional ketosis resumed.
- Testosterone, estradiol, progesterone, and related reproductive hormone patterns did not show harmful disruption in that cohort.
Thyroid, HOMA-IR, and RQ
- Low T3 in a ketogenic phenotype is not automatically hypothyroidism.
- Low T3 can reflect efficient fat and ketone metabolism when HOMA-IR, ketones, and clinical context are healthy.
- Low T3 with suppressed ketogenesis can reflect insulin-driven thyroid stress and impaired iodine handling.
- Respiratory quotient can show whether fasted resting metabolism is mainly using fat, carbohydrate, or protein.
Cancer metabolism and therapeutic ketosis
- Ketosis is not a stand-alone cancer cure, and standard cancer care still has a place.
- Therapeutic ketosis can improve chemotherapy efficacy and reduce toxicity burden in this model.
- Cancer is defined here by chronic overproliferation plus loss of apoptosis.
- Metabolic health and low insulin demand can lower the drive toward overproliferation and impaired cell cleanup.
Insulin, mitochondria, and cancer signaling
- Excess glucose and insulin raise mitochondrial oxidative stress and inflammatory signaling.
- HIF-1 alpha, NF-kappa-beta, inflammasomes, and TNF-alpha push cells toward glycolysis and division.
- Overactive HIF-1 alpha and mitochondrial stress shut down autophagy, mitophagy, and mitochondrial biogenesis.
- Replicating damaged cellular machinery compounds dysfunction.
Glucose, glutamine, and dairy in cancer
- Glucose feeds much of the cancer energy demand, while insulin gives proliferation and anti-apoptosis signals.
- Glutamine is life-essential, but glutaminolysis in this model sits downstream of glucose and insulin pressure.
- People with cancer are advised here to avoid milk, yogurt, kefir, and cheese.
- Dairy is portrayed as hyperanabolic because whey, casein, IGF-1, lactose, and glutamine together activate growth pathways.
Serum insulin testing and prevention
- Serum insulin should be checked with glucose, HbA1c, thyroid, and bone-related bloodwork.
- Elevated insulin can occur before overt diabetes, prediabetes, cancer, dementia, cardiovascular disease, and bone fragility.
- UK access to insulin testing is limited unless diabetes or prediabetes is already recognized.
- Wider insulin testing and cheaper point-of-care insulin assays would support prevention.
Medical education and chronic disease care
- Endocrine education remains glucose-centered in this account.
- Professional education often centers new drugs for hyperglycemia or reflux and leaves root pathology unresolved.
- Acute medication has a valid role, but chronic disease care should improve the condition and reduce medication burden over time.
- A patient whose chronic condition worsens while medications multiply may need a different clinical approach.
References
- [00:00] Rethinking Fragility Fractures in Type 2 Diabetes: The Link between Hyperinsulinaemia and Osteofragilitas — https://doi.org/10.3390/biomedicines9091165
- [00:04] Insulin use and Excess Fracture Risk in Patients with Type 2 Diabetes: A Propensity-Matched cohort analysis — https://doi.org/10.1038/s41598-017-03748-z
- [00:05] Fracture risk in diabetic elderly men: the MrOS study — https://doi.org/10.1007/s00125-014-3289-6
- [00:10] Effects of Intensive Glucose Lowering in Type 2 Diabetes — https://doi.org/10.1056/NEJMoa0802743
- [00:15] Bio-Hacking Better Health—Leveraging Metabolic Biochemistry to Maximise Healthspan — https://doi.org/10.3390/antiox12091749
- [00:27] How and Why We Age — https://www.worldcat.org/oclc/1035597432
- [00:32] Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females — https://doi.org/10.3390/ijms242115621
- [00:32] Ketosis Suppression and Ageing (KetoSAge): The Effect of Suppressing Ketosis on GKI and Liver Biomarkers in Healthy Females — https://doi.org/10.3390/LIVERS5030041
- [00:32] Ketosis suppression and ageing (KetoSAge): the effect of suppressing ketosis on SHBG and sex hormone profiles in healthy premenopausal women, and its implications for cancer risk and therapy — https://doi.org/10.3389/fnut.2025.1731915
- [00:34] Ketosis Suppression and Ageing (KetoSAge) Part 2: The Effect of Suppressing Ketosis on Biomarkers Associated with Ageing, HOMA-IR, Leptin, Osteocalcin, and GLP-1, in Healthy Females — https://doi.org/10.3390/biomedicines12071553
:::