Fixing problems in cholesterol metabolism could stave off a leading cause of blindness (AMD help)

Medical Xpress / Washington University in St. Louis / Nature Communications ^ | June 24, 2025 | Lee TJ, et al

[ConservativeMind]

A study identifies a possible way to slow or block progression of age-related macular degeneration.

The researchers implicated problems with cholesterol metabolism in this type of vision loss, perhaps helping explain the links between macular degeneration and cardiovascular disease, which both worsen with age.

The new findings—identified using human plasma samples and mouse models of macular degeneration—suggest that increasing the amount of a molecule called apolipoprotein M (ApoM) in the blood fixes problems in cholesterol processing that lead to cellular damage in the eyes and other organs.

In recent years, evidence has emerged that ApoM can serve as a protective molecule with known anti-inflammatory effects and roles in maintaining healthy cholesterol metabolism.

They showed that patients with macular degeneration have reduced levels of ApoM circulating in blood compared with healthy controls. And past work showed patients with various forms of heart failure also had reduced levels of ApoM in the blood.

This study revealed ApoM is a key component in the "good cholesterol" pathways that mop up excess cholesterol—the bad kind that tends to drive inflammation—and clear it from the body.

Javaheri's research suggests when ApoM is low, cells in the retina and heart muscle can't correctly metabolize cholesterol deposits and have a hard time getting rid of these accumulating lipids. When these lipids build up, it leads to inflammation and cellular damage.

To see if they could reverse the harmful effects of low ApoM, the researchers increased ApoM levels in mouse models of macular degeneration.

The mice showed evidence of improved retinal health, improved function of light-sensing cells in the retina and reduced accumulation of cholesterol deposits. The researchers further found evidence that ApoM triggers a signaling pathway that breaks down the cholesterol in cellular compartments called lysosomes, which are known for playing roles in disposing of cellular waste.

[OftheOhio]

I just wanted you to know my previous comment was not a slam on you. In fact, one of your previous articles about choelesterol had some epic comments and was thought-provoking, especially about cancer.

I find it unbelievable that we haven’t cured cancer with all the monies that have gone to research for decades.

[ConservativeMind]

It is all fine, my FRiend.

[OftheOhio]

Oh, I forgot. Make Cursive Great Again.
That was a great article too on how it may help old timers like me from getting old timers.

[Mr Rogers]

“Unfortunately, according to the studies, it doesn’t work for the majority.”

Actually, if it DOES work for me, then it means it is NOT the problem the other people are encountering.

If X is THE CAUSE of Y, then someone doing X - or in this case, millions doing X - and having Y not happen means X does NOT cause Y.

There are now MILLIONS of people who deliberately skip breakfast every day and are not seeing anything bad. In fact, we’re seeing many good things.

Skipping breakfast because you are too weak to get out of bed means a bad thing is happening, but the bad thing is being too weak (or too poor) to be able to eat breakfast. What the studies you linked really show is “Wet sidewalks cause rain”.

No one bothers to study the many people doing “Time Restricted Eating” - a form of Intermittent Fasting - to see if it is “skipping breakfast” that causes the problem. Maybe because there are no breakfast cereal companies willing to pay for it.

[onthelookout777]

Sorry. I should have reworded what I said.

You list the benefits you’ve experienced from your diet and from intermittent fasting, and I didn’t mean that you, and others, haven’t experienced those benefits.

I just meant that a lot of studies show that for the majority of people who skip breakfast, there are significant downsides, some of which take time to develop. So it seems best to do intermittent fasting in a way that doesn’t involve skipping breakfast.

[ConservativeMind]

On the AMD front, this is a study I posted a few years back that made me start eating a small amount of dried goji berries nearly every day.

I eat them as part of dessert after a meal that had fat.

Dried goji berries may provide protection against age-related vision loss (1 oz/day provides 28.8 mg Zeaxanthin - Lutein 6mg/Zeaxanthin 4mg supplement did nothing)

https://freerepublic.com/focus/f-chat/4029249/posts

Another thing my wife and I constantly get now is ergothioneine from foods and supplements. It is a backup antioxidant to all sorts of antioxidants our body needs. Unlike all other antioxidants, it lasts over three weeks, once in place. Nearly all of our body's cells have an ion pathway to allow in only this substance. Internally-made antioxidants SOD or glutathione last a couple hours, at most.

Ergothioneine appears to also help the retina and other parts of the eye.

Screening and evaluation of antioxidants for retinal pigment epithelial cell protection: L-ergothioneine as a novel therapeutic candidate through NRF2 activation

https://www.sciencedirect.com/science/article/abs/pii/S0014483524000836

“The continual exposure of retinal tissues to oxidative stress leads to discernible anatomical and physiological alterations. Specifically, the onslaught of oxidative damage escalates the irreversible death of retinal pigmented epithelium (RPE) cells, pinpointed as the fundamental pathological event in dry age-related macular degeneration (AMD). There is a conspicuous lack of effective therapeutic strategies to counteract this degenerative process. This study screened a library of antioxidants for their ability to protect RPE cells against oxidative stress and identified L-ergothioneine (EGT) as a potent cytoprotective agent. L-ergothioneine provided efficient protection against oxidative stress-damaged RPE and maintained cell redox homeostasis and normal physiological functions. It maintained the normal structure of the retina in mice under oxidative stress conditions. Transcriptomic analysis revealed that EGT counteracted major gene expression changes induced by oxidative stress. It upregulated antioxidant gene expression and inhibited NRF2 translocation… In conclusion, we identified EGT as a safe and effective small-molecule compound that is expected to be a novel antioxidative agent for treating AMD.”

This is in oyster and shiitake mushrooms, and in small quantities in white and brown button mushroom. If you don't eat mushrooms often, Double Wood has L-Ergothioneine at $10 for a 60 count of 30 mg capsules (Amazon). This is an incredible deal, as just a couple years ago this was not available in supplement form in any reasonable amount. I recall a few years back seeing it at $125 for half this amount in 25 mg capsules from a research company.

[BrandtMichaels]

Damned if you do and damned if you don’t - seems that so
many studies contradict each other, it’s all just maddening!

All of my heart, stress, health tests always came out with
very good numbers, except for ‘high blood pressure’ similarly
a co-worker had all great numbers except for cholesterol.

Then I read somewhere recently (no I didn’t save it - sorry)
that ‘science’ lowered the numbers rather arbitrarily iirc.

So I asked Grok to get better background info to share and
lo and behold if you have a healthy heart and no history
of heart attacks/disease then likely no need to worry nor
take a prescription.

Read my next post if you have the time and see if you agree per Grok...

[BrandtMichaels]

Per Grok (sorry, Grok messes up the formatting) ... Yes, the thresholds for acceptable cholesterol and blood pressure levels have been lowered over time, driven by evolving scientific evidence, clinical studies, and shifts in medical guidelines. Below, I’ll outline the key scientific basis for these changes, focusing on major studies and guideline updates.Cholesterol ThresholdsHistorical Context: In the 1980s, total cholesterol levels below 240 mg/dL were often considered acceptable. Over time, guidelines tightened, with current recommendations emphasizing LDL ("bad") cholesterol below 100 mg/dL (or 70 mg/dL for high-risk individuals) and total cholesterol below 200 mg/dL.Scientific Studies Supporting Lower Cholesterol Thresholds:Framingham Heart Study (1948–ongoing):This landmark study established cholesterol as a key risk factor for cardiovascular disease (CVD). It showed that higher total cholesterol levels correlated with increased heart attack risk, prompting early guidelines to target lower levels. Later analyses refined this, emphasizing LDL cholesterol’s role in atherosclerosis, leading to more specific targets. Statins and Clinical Trials (1990s–2000s):Scandinavian Simvastatin Survival Study (4S, 1994): This trial demonstrated that lowering LDL cholesterol with statins in patients with existing heart disease significantly reduced mortality and heart attack risk. It supported targeting LDL levels below 130 mg/dL, a shift from earlier, less stringent goals. Heart Protection Study (2002): Showed that even individuals with “normal” LDL levels (around 130 mg/dL) benefited from further reductions, pushing guidelines toward lower LDL targets (e.g., <100 mg/dL for high-risk patients). PROVE-IT TIMI 22 (2004): Compared intensive (LDL <70 mg/dL) vs. moderate (LDL <100 mg/dL) statin therapy, finding better outcomes with lower LDL in high-risk patients, influencing guidelines to recommend <70 mg/dL for those with established CVD. Epidemiological and Genetic Evidence:Studies like the MRFIT (Multiple Risk Factor Intervention Trial) showed a continuous relationship between cholesterol levels and CVD risk, with no clear “safe” threshold, suggesting that lower is better for most populations. Genetic studies (e.g., PCSK9 mutation research) showed that individuals with naturally very low LDL levels (e.g., <50 mg/dL) have significantly reduced CVD risk, supporting aggressive lowering in high-risk groups. Guideline Evolution:The National Cholesterol Education Program (NCEP) in the 1980s set total cholesterol <240 mg/dL as a threshold. By the 2000s, ATP III guidelines shifted focus to LDL (<100 mg/dL for high-risk groups). The 2013 ACC/AHA Cholesterol Guidelines moved away from strict LDL targets, emphasizing risk-based statin therapy, but 2018 updates reinstated LDL <70 mg/dL for very high-risk patients based on newer trial data (e.g., FOURIER and ODYSSEY trials with PCSK9 inhibitors). Blood Pressure ThresholdsHistorical Context: In the 1970s–1980s, blood pressure thresholds for hypertension were higher (e.g., >160/100 mmHg). Over time, guidelines lowered the cutoff to 140/90 mmHg and, more recently, to 130/80 mmHg for many adults.Scientific Studies Supporting Lower Blood Pressure Thresholds:Veterans Administration Cooperative Study (1960s–1970s):Early trials showed that treating severe hypertension (>160/100 mmHg) reduced stroke and heart failure risk, establishing the benefits of blood pressure control and prompting initial guidelines. Hypertension Detection and Follow-Up Program (HDFP, 1979):Demonstrated that treating milder hypertension (diastolic 90–104 mmHg) reduced mortality, shifting focus to lower thresholds than previously considered. SPRINT Trial (2015):A pivotal study comparing intensive (<120 mmHg systolic) vs. standard (<140 mmHg systolic) blood pressure control in high-risk patients. Intensive treatment reduced cardiovascular events by 25% and mortality by 27%, strongly supporting lower targets. This trial heavily influenced the 2017 ACC/AHA Hypertension Guidelines, which redefined hypertension as ≥130/80 mmHg (previously ≥140/90 mmHg) for most adults. Meta-Analyses and Cohort Studies:Lancet 2016 Meta-Analysis: Analyzed multiple trials and confirmed that lowering blood pressure below 130/80 mmHg reduced CVD risk across populations, even in those without prior hypertension. Observational studies (e.g., Framingham) showed a linear increase in CVD risk starting at systolic pressures as low as 115 mmHg, supporting the “lower is better” approach for high-risk groups. Guideline Evolution:JNC 7 (2003): Defined hypertension as ≥140/90 mmHg, with treatment goals of <140/90 mmHg for most and <130/80 mmHg for high-risk groups (e.g., diabetes, kidney disease). 2017 ACC/AHA Guidelines: Lowered the hypertension threshold to ≥130/80 mmHg based on SPRINT and other data, emphasizing earlier intervention to prevent CVD. European Guidelines (2018): Maintained 140/90 mmHg as the general threshold but recommended <130/80 mmHg for many patients, reflecting similar evidence. Why Thresholds LoweredBetter Understanding of Risk: Long-term studies (e.g., Framingham, MRFIT) showed that even “normal” cholesterol and blood pressure levels carried significant CVD risk, especially in combination with other factors like age, smoking, or diabetes. Improved Treatments: Statins, PCSK9 inhibitors, and better antihypertensive drugs made achieving lower targets feasible and safe, supported by trials showing benefits outweighed risks. Population-Level Data: Epidemiological studies and meta-analyses confirmed that lower cholesterol and blood pressure levels correlate with reduced CVD events across diverse populations. Focus on Prevention: Guidelines shifted toward preventing events in lower-risk populations, not just treating those with established disease, leading to stricter thresholds. Caveats and ControversiesCholesterol: Some argue that overly aggressive LDL lowering (e.g., <70 mg/dL) may not benefit low-risk individuals and could increase side effects (e.g., statin-related muscle pain). The 2013 ACC/AHA guidelines’ shift away from strict LDL targets sparked debate, though later updates balanced risk-based and target-driven approaches. Blood Pressure: The SPRINT trial’s intensive targets (<120 mmHg systolic) raised concerns about risks like hypotension, kidney injury, or falls, particularly in older adults. JNC 8 (2014) and European guidelines have been more cautious, recommending individualized targets. Guideline Variability: Different organizations (e.g., ACC/AHA vs. European Society of Cardiology) interpret the same data differently, leading to varying thresholds and debates over “overtreatment.” ConclusionThe lowering of cholesterol and blood pressure thresholds is supported by robust scientific evidence from large-scale clinical trials (e.g., 4S, SPRINT), epidemiological studies (e.g., Framingham), and meta-analyses showing reduced CVD risk with lower levels. These findings, combined with advances in treatment, have driven guideline updates to prioritize prevention and tighter control. However, some controversies remain about balancing benefits and risks, especially in low-risk or elderly populations.

[dfwgator]

140/90 used to considered “normal blood pressure”.

Now if it’s above 110/70 they want you on drugs.

[BrandtMichaels]

All of the above in post #28 leads one to ask:

If all this science is true then why are we all still
under constant scrutiny for high BP & Cholesterol when
heart disease is still the leading cause of death - are
the statistics even going down for the last 70-80 years?

One could ask the same for cancer - the #2 leading cause
of death. No Thank You modern medicine - give me my
functional mushrooms, ivermectin, fembendazole and every
other holistic approach that modern medicine has not, in
the least, proven detrimental to overall health - just the
opposite imo!

[BrandtMichaels]

Reading these studies and the ‘expert’ opinions does
raise my blood pressure - highest iirc 225/135 and yet
by their accounts I should be rushed to the hospital to
save my life (and drain my bank account).

Worst side effect I’ve noticed is sometimes I wake up
with a dull headache that usually fades away on it’s own!

[BrandtMichaels]

Currently 158/94 so no worries from my perspective.

[BobL]

Thanks, I’ll stick with my personal targets for BP of 150/95. There was a huge study reported by 60 minutes decades ago (maybe the Swedish Nurses Study) where they tracked people over many years...the ones that lived longer had higher Blood Pressure. As far as Cholesterol goes, until they properly test LDL (meaning testing for particle size), its number is meaningless, and LDL does some very important things to for the human body. The BIG FACTORS in lipids is HDL and especially Triglycerides (fat in blood).

[ConservativeMind]

What is thought to be the reason for your blood pressure?

Have you had a coronary calcium scan?

I would encourage backing those numbers down a bit.

[BrandtMichaels]

Experts and MSM who are addicted to lying and causing
the general public to fear anything and everything -
just my guess - since not much bothers me anymore and
my BP readings are trending downward.

[tired&retired]

“I thought masturbation was the leading cause of blindness”

That’s what my Buddy said. However, he said he would stop when he needs glasses!