Latest / Glaucoma, Vision & Longevity: Supplements & Science / Ketogenic Signals and Beta-Hydroxybutyrate: IOP, Neuroprotection, and Longevity Intersections

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Ketogenic Signals and Beta-Hydroxybutyrate: IOP, Neuroprotection, and Longevity Intersections · Glaucoma, Vision & Longevity: Supplements & Science

• 0:00
  SPEAKER_00: Ketogenic diet and retina, protecting eye nerves through metabolism.
• 0:04
  SPEAKER_00: Glaucoma is an eye disease where pressure or other factors cause progressive damage to the retinal nerve cells, retinal ganglion cells, RGCs, and their fibers, leading to vision loss.
• 0:16
  SPEAKER_00: Traditionally, treatment focuses on lowering eye pressure, intraocular pressure, IOP.
• 0:21
  SPEAKER_00: Recently, researchers have explored whether changing body metabolism, for example, with a ketogenic diet or ketone supplements, could help protect RGCs.
• 0:30
  SPEAKER_00: A ketogenic diet is very low in carbohydrates and high in fats.
• 0:34
  SPEAKER_00: In response, the body burns fat and produces ketone bodies, like beta-hydroxybutyrate or BHB as a fuel.
• 0:41
  SPEAKER_00: Ketones can serve as an alternative energy source for the brain and eyes.
• 0:45
  SPEAKER_00: Emerging evidence suggests these metabolic changes can boost cell energy use, quiet harmful overactivity, excitotoxicity, and even alter gene activity in ways that may shield RGCs from damage.
• 0:57
  SPEAKER_00: In animal studies, ketone treatments have improved RGC survival and function.
• 1:03
  SPEAKER_00: In other model systems, BHB shows broad anti-inflammatory and longevity effects.
• 1:09
  SPEAKER_00: In this article, we explain these findings in plain terms and discuss what they mean for glaucoma patients, especially those who are older or have other health issues.
• 1:18
  SPEAKER_00: Fueling mitochondria, energy efficiency and retinal health.
• 1:22
  SPEAKER_00: The retina, especially RGCs, is a highly active tissue that needs a lot of energy to work.
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  SPEAKER_00: This energy comes from tiny structures in cells called mitochondria.
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  SPEAKER_00: If mitochondria work better, nerve cells are healthier.
• 1:35
  SPEAKER_00: Ketones are a special fuel for mitochondria.
• 1:38
  SPEAKER_00: They can be turned into energy efficiently, sometimes even more cleanly than sugar.
• 1:43
  SPEAKER_00: A number of studies have shown that ketogenic metabolism boosts mitochondrial function.
• 1:48
  SPEAKER_00: For example, one study in mice used a glaucoma model and found that a ketogenic diet promoted both mitochondrial biogenesis, making new mitochondria, and mitophagy, recycling damaged mitochondria in RGCs.
• 2:01
  SPEAKER_00: In that glaucoma model, mice eating a high-fat, low-carb diet kept more RGCs alive than control mice.
• 2:08
  SPEAKER_00: The investigators noted increased mitochondrial markers and better energy balance in those cells.
• 2:14
  SPEAKER_00: In simpler terms, the ketogenic diet gave the eye nerves a metabolic upgrade, more and healthier mitochondria that could meet energy needs under stress.
• 2:24
  SPEAKER_00: Animal research also links ketosis to better antioxidant defenses, fighting cell damage.
• 2:30
  SPEAKER_00: For example, a scientific review points out that ketogenic metabolism can lower production of harmful reactive oxygen species and boost cell protective pathways.
• 2:39
  SPEAKER_00: In experimental glaucoma, an inherited model in DBA2J mice, mice on a ketogenic diet showed healthier mitochondria and more antioxidant response compared to controls.
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  SPEAKER_00: These changes were accompanied by better RGC survival.
• 2:53
  SPEAKER_00: This suggests that providing ketones, either through diet or supplements, may make retinal neurons more energy efficient and resistant to stress.
• 3:02
  SPEAKER_00: Calming excitotoxicity, dampening overactive nerve signals.
• 3:07
  SPEAKER_00: Another stress factor for neurons is excitotoxicity.
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  SPEAKER_00: This happens when too much glutamate, a common nerve messenger, over-excites cells and leads to injury.
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  SPEAKER_00: In glaucoma and other neurodegenerative diseases, excitotoxicity can kill retinal cells.
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  SPEAKER_00: Laboratory studies show ketones can attenuate this effect.
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  SPEAKER_00: In one rat study, scientists gave animals a toxic dose of NMDA, a glutamate-like chemical, to kill RGCs, mimicking excitotoxic damage.
• 3:34
  SPEAKER_00: Rats that received injections of beta-hydroxybutyrate, BHB, or acetoacetate, had significantly less nerve cell death than untreated rats.
• 3:44
  SPEAKER_00: In other words, ketone bodies protected RGCs from a glutamate-related assault.
• 3:49
  SPEAKER_00: The researchers found that BHB helped preserve levels of protective molecules like kinerinic acid, which naturally block excitotoxic signals.
• 3:57
  SPEAKER_00: This suggests that ketones can act like a break on harmful nerve overactivation.
• 4:02
  SPEAKER_00: The exact mechanisms still need more research, but the effect is consistent with the known anti-seizure benefits of ketogenic diets in epilepsy, which also involve reducing excitotoxic activity in the brain.
• 4:15
  SPEAKER_00: For glaucoma, dampening excitotoxicity could mean nerve cells are less likely to be killed by the constant stress of high eye pressure or other insults.
• 4:25
  SPEAKER_00: Thus, ketogenic therapy may protect RGCs by both boosting their energy and keeping their electrical activity in a safer range.
• 4:33
  SPEAKER_00: Epigenetic effects.
• 4:34
  SPEAKER_00: BHB as a gene regulator.
• 4:36
  SPEAKER_00: Beyond immediate fuel, ketones have surprising epigenetic effects.
• 4:40
  SPEAKER_00: They change how genes are expressed.
• 4:42
  SPEAKER_00: The key player here is BHB.
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  SPEAKER_00: Beta-hydroxybutyrate can influence the modifications like acetylation of histone proteins that package DNA as well as other gene-regulating proteins.
• 4:54
  SPEAKER_00: These changes can turn on long-term resilience programs in cells.
• 4:58
  SPEAKER_00: For example, BHB is known to inhibit certain histone deacetylase enzymes, HDX, which normally act to silence genes.
• 5:06
  SPEAKER_00: By blocking HDX, BHB tends to loosen up chromatin and allow protective genes to be more active.
• 5:12
  SPEAKER_00: In brain and cellular studies, BHB's HDAC inhibition has been linked to anti-inflammatory and antioxidant gene expression.
• 5:19
  SPEAKER_00: In fact, research cited in science showed that BHB treatment raised the acetylation of histones in the brain and activated key stress response factors.
• 5:29
  SPEAKER_00: In retinal cells specifically, inhibiting HDACs has been shown to preserve RGC structure.
• 5:35
  SPEAKER_00: While direct studies of BHB's epigenetic effects on the retina are still emerging, the known action of BHB implies it could turn on genes that protect nerves.
• 5:44
  SPEAKER_00: Animal experiments reinforce that this epigenetic switch matters for longevity.
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  SPEAKER_00: In the roundworm C.
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  SPEAKER_00: elegans, giving BHB extended the worm's lifespan.
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  SPEAKER_00: The mechanism required the worm's equivalent of FOXODAF-16 and NRF-2, SKN1, key longevity regulators, and also depended on BHB's HDAC inhibition.
• 6:04
  SPEAKER_00: In other words, BHB extended life by activating well-known longevity pathways, and it could not do that without affecting histone acetylation.
• 6:13
  SPEAKER_00: This suggests that in higher animals, too, BHB might promote a protected gene expression profile in nerve cells, helping them survive longer under stress.
• 6:22
  SPEAKER_00: Anti-inflammatory role calming chronic damage.
• 6:26
  SPEAKER_00: Chronic inflammation is another problem in aging and glaucoma.
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  SPEAKER_00: Damaged tissues often raise inflammatory signals that can harm neurons.
• 6:33
  SPEAKER_00: Here again, BHB has useful actions.
• 6:36
  SPEAKER_00: One major target is the NLRP3 inflammosome, a protein complex that drives inflammation.
• 6:42
  SPEAKER_00: Studies show BHB blocks the NLRP3 inflammosome, thereby lowering pro-inflammatory cytokines like IL-1 beta and IL18.
• 6:50
  SPEAKER_00: In fact, Umet et al.
• 6:59
  SPEAKER_00: Specific to the eye, a recent study in diabetic mice looked at this explicitly.
• 7:03
  SPEAKER_00: The researchers injected BHB and found it dramatically reduced markers of inflammosome activity in the retina.
• 7:10
  SPEAKER_00: After BHB treatment, diabetic mice had about half the levels of retinal NLRP3, ASC, and CAS base 1 inflammosome components, and much lower IL1 beta and IL18 compared to untreated diabetic mice.
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  SPEAKER_00: In short, the ketones stop the chain of inflammation signals that normally builds up in diabetes.
• 7:31
  SPEAKER_00: This is promising because many glaucoma patients also have diabetes or other conditions that cause chronic eye inflammation.
• 7:38
  SPEAKER_00: By acting on HCA2 receptors and inflammosomes, BHB could help quiet retinal stress.
• 7:43
  SPEAKER_00: Additionally, BHB can bind to G protein receptors like HCA2 that have anti-inflammatory effects in tissues.
• 7:50
  SPEAKER_00: It also has been reported to scavenge free radicals and support antioxidant pathways.
• 7:56
  SPEAKER_00: All these signals together mean ketones teach cells to switch from an angry-injured mode to a protected healing mode.
• 8:03
  SPEAKER_00: In model organisms, this shift is linked to health span.
• 8:06
  SPEAKER_00: For example, rodents on cycles of ketosis showed less brain inflammaging and better cognitive performance in old age.
• 8:14
  SPEAKER_00: While more human studies are needed, the anti-inflammatory properties of BHB are now well documented.
• 8:20
  SPEAKER_00: Ketones and longevity lessons from lab models.
• 8:23
  SPEAKER_00: Laboratory studies of aging hint that ketosis could be part of a pro-longevity regimen.
• 8:29
  SPEAKER_00: In simple organisms, supplementing with BHB can extend life.
• 8:33
  SPEAKER_00: C.
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  SPEAKER_00: Elegans given D beta hydroxybutyrate lived significantly longer and showed better stress resistance.
• 8:40
  SPEAKER_00: Their longevity increase required the same FOXO and AMPK pathways known from calorie restriction and needed BHB's HDAC effects.
• 8:49
  SPEAKER_00: This supports the idea that ketones mimic some benefits of fasting, like activating housekeeping genes.
• 8:55
  SPEAKER_00: In mice, the data is mixed but intriguing.
• 8:58
  SPEAKER_00: One study put middle-aged mice on a cyclic ketogenic diet, alternating ketogenic weeks, and found that fewer mice died in midlife and their memory stayed sharper into old age, compared to controls.
• 9:10
  SPEAKER_00: The ketogenic mice showed gene expression changes in common with fasting or high-fat feeding, including activation of PPRR targets involved in fat metabolism.
• 9:20
  SPEAKER_00: Importantly, memory tests like object recognition were much better in the ketogenic group, even at toward two years old.
• 9:28
  SPEAKER_00: This suggests ketosis helped preserve cognitive function with age.
• 9:32
  SPEAKER_00: No such study exists yet in humans for glaucoma, but it hints at possible brain benefits.
• 9:39
  SPEAKER_00: Finally, a general review noted that ketones and related short-chain fatty acids repeatedly show positive effects on health and lifespan across species.
• 9:48
  SPEAKER_00: However, it also warns that long-term use needs study.
• 9:52
  SPEAKER_00: Indeed, a very recent mouse study found that lifelong unrelenting ketogenic diet led to high blood lipids and liver issues in mice, along with drop in insulin secretion.
• 10:02
  SPEAKER_00: That means any recommendation must balance benefits with risks, especially over many years.
• 10:07
  SPEAKER_00: Clinical considerations.
• 10:09
  SPEAKER_00: Who should try it and how?
• 10:11
  SPEAKER_00: Glaucoma patients are often older and can have other health issues like diabetes, high blood pressure, or kidney concerns.
• 10:19
  SPEAKER_00: Any change to a strict keto diet needs careful thought.
• 10:22
  SPEAKER_00: Here are some key points.
• 10:23
  SPEAKER_00: Diabetic patients.
• 10:25
  SPEAKER_00: Type 1 diabetics must be extremely cautious.
• 10:28
  SPEAKER_00: Lack of insulin plus a keto diet could trigger diabetic ketoacidosis, a dangerous condition.
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  SPEAKER_00: Type 2 diabetics also need monitoring.
• 10:37
  SPEAKER_00: However, short-term keto under medical supervision can improve blood sugar control in some patients.
• 10:43
  SPEAKER_00: Anyone with diabetes should only attempt ketogenic diets with a doctor's guidance and frequent blood tests.
• 10:49
  SPEAKER_00: Heart and blood lipids.
• 10:51
  SPEAKER_00: Because ketogenic diets are high in fat, some studies report rises in LDL bad cholesterol.
• 10:56
  SPEAKER_00: Others show improved markers, like lower triglycerides in overweight people 41.
• 11:02
  SPEAKER_00: Still, a patient with known atherosclerosis or very high LDL should consult a cardiologist.
• 11:08
  SPEAKER_00: It would be wise to check cholesterol regularly.
• 11:10
  SPEAKER_00: Some experts advise focusing on healthy fats, olive oil, nuts, rather than saturated fats if trying low-carb eating.
• 11:18
  SPEAKER_00: Kidney issues.
• 11:19
  SPEAKER_00: High protein or ketogenic diets can change mineral balance.
• 11:23
  SPEAKER_00: One well-known effect is an increased risk of kidney stones.
• 11:26
  SPEAKER_00: For example, a child on a strict keto diet developed painful kidney stones within months.
• 11:32
  SPEAKER_00: For glaucoma patients with any kidney disease or history of stones, caution is needed.
• 11:37
  SPEAKER_00: Good hydration and dietary advice, such as citrate supplements, might help, but this should be managed by a doctor or dietitian.
• 11:45
  SPEAKER_00: Nutritional balance.
• 11:47
  SPEAKER_00: Ketogenic diets can be low in fiber, vitamins, or minerals if not planned properly.
• 11:52
  SPEAKER_00: Long-term ketogenic eating should be accompanied by a vitamin-mineral supplement and possibly a registered dietitian's guidance.
• 11:59
  SPEAKER_00: Goals like controlled carbohydrates, as in a Mediterranean or modified Atkins diet, might be safer alternatives.
• 12:07
  SPEAKER_00: Medication interactions.
• 12:09
  SPEAKER_00: Fasting-like states can alter how some drugs work.
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  SPEAKER_00: For instance, glaucoma patients on eye drops or pills to lower pressure should know that severe dietary changes might affect blood pressure or fluid balance.
• 12:22
  SPEAKER_00: Patients should not change their glaucoma treatment without consulting their eye doctor.
• 12:27
  SPEAKER_00: In sum, while ketogenic signals show promise in lab studies, most glaucoma patients shouldn't go keto on their own.
• 12:35
  SPEAKER_00: A doctor or clinic should supervise any such intervention, ideally with input from nutritionists and primary care.
• 12:42
  SPEAKER_00: Those with heart disease or kidney problems should especially get clearance.
• 12:47
  SPEAKER_00: The no free lunch rule applies.
• 12:49
  SPEAKER_00: If one tries to increase ketones, the potential benefits must be weighed against known metabolic changes.
• 12:56
  SPEAKER_00: Pilot trials, testing ketones in glaucoma patients.
• 13:00
  SPEAKER_00: To move forward, carefully designed research is needed.
• 13:03
  SPEAKER_00: Instead of everyone immediately adopting a keto diet, small pilot clinical trials could test feasibility and outcomes.
• 13:10
  SPEAKER_00: A useful study might enroll glaucoma patients with and without issues like diabetes and give a monitored ketogenic diet or ketone supplement for a few months.
• 13:20
  SPEAKER_00: Key measures would include metabolic phenotyping, regular blood tests to check ketone levels, glucose, cholesterol, triglycerides, and kidney liver function.
• 13:30
  SPEAKER_00: Insulin sensitivity tests could show if the diet is helping or harming metabolic health.
• 13:35
  SPEAKER_00: This ensures safety.
• 13:37
  SPEAKER_00: Retinal imaging techniques like OCT, optical coherence tomography can measure nerve fiber layer thickness, a marker of RGC health.
• 13:45
  SPEAKER_00: Researchers could see if these structural measures stabilize or decline more slowly on keto-verse control.
• 13:52
  SPEAKER_00: Functional tests like visual fields, perimetry, or a contrast sensitivity test could also be recorded.
• 13:58
  SPEAKER_00: Neuroprotection markers.
• 14:00
  SPEAKER_00: Special retinal scans can detect metabolic stress, for example, retinal oximetry.
• 14:04
  SPEAKER_00: Researchers might also measure cerebrospinal or blood biomarkers of neuroprotection, e.g., BDNF levels, inflammatory markers like IL1 beta.
• 14:14
  SPEAKER_00: Cognitive aging measures, since BHB affects the brain too, simple cognitive tests, memory, attention, could be included.
• 14:21
  SPEAKER_00: If keto really boosts brain health in middle older age, patients might perform better on standardized memory tests or show improved mood, fatigue scores.
• 14:30
  SPEAKER_00: Before and after comparisons and control groups, perhaps an exercise and healthy diet group would help isolate effects.
• 14:38
  SPEAKER_00: Even if a pilot is too small to prove glaucoma benefit, it would show who can tolerate the diet and whether retinal measures change in a positive direction.
• 14:47
  SPEAKER_00: Ideally, these trials would be double-blinded if using a ketone supplement, like ketone esters or salts versus placebo, to control for diet differences.
• 14:57
  SPEAKER_00: To summarize, basic science suggests ketones from diet or pills could help retinal neurons by improving their energy use, damping harmful signals, and turning on protective genes.
• 15:09
  SPEAKER_00: BHB in particular is a natural anti-inflammatory signal that activates longevity pathways.
• 15:15
  SPEAKER_00: These effects have been seen in animal glaucoma models and aging studies.
• 15:20
  SPEAKER_00: However, ketogenic approaches are not risk-free and require medical oversight.
• 15:25
  SPEAKER_00: In glaucoma patients with multiple health issues, any new diet should be matched to their overall condition.
• 15:32
  SPEAKER_00: Carefully conducted pilot studies with metabolic and imaging measurements, plus memory cognition tests, could clarify whether advancing ketone metabolism safely slows vision loss or cognitive aging.
• 15:45
  SPEAKER_00: As of now, patients should not make drastic dietary changes without professional guidance.
• 15:50
  SPEAKER_00: All links to sources are available in the text version of this article.
• 15:54
  SPEAKER_00: You can find the full article at VisualFieldTest.com.
• 15:58
  SPEAKER_00: Thanks for listening.
• 15:59
  SPEAKER_00: To check your visual field, click the link at the bottom of this article or visit VisualFieldtest.com.