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The Surprising Role of Cortisol in Alzheimer’s
Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/11/26/role-of-cortisol-in-alzheimers.aspx
Analysis by Dr. Joseph Mercola November 26, 2025
Story at-a-glance
- New research shows that people with Alzheimer’s have higher cortisol levels and a skewed cortisol-to-DHEA-S ratio, revealing that chronic stress drives early brain degeneration long before memory loss appears
- Cortisol, your body’s main stress hormone, damages neurons and disrupts energy metabolism when it stays elevated, while DHEA-S acts as a protective neurosteroid that helps your brain resist inflammation and oxidative stress
- Bioenergetic researcher Georgi Dinkov connected these findings to thyroid and metabolic health, showing that when your cells don’t produce enough energy, cortisol rises and accelerates cognitive decline
- Tracking your cortisol-to-DHEA-S ratio offers a powerful early warning sign for chronic stress and neurodegeneration, allowing you to take preventive action years before symptoms develop
- You can rebalance these hormones naturally by fueling your metabolism with adequate healthy carbohydrates, improving sleep and light exposure, reducing overtraining, practicing calming breathwork, and using natural progesterone to help quiet cortisol
Alzheimer’s disease doesn’t begin with memory loss — it begins years earlier with a slow, silent shift in your body’s stress chemistry. Long before neurons die, your brain’s hormonal balance starts to erode under constant pressure from everyday stress. The same hormones that once kept you alert and focused start working against you, wearing down your brain’s repair systems and disrupting the flow of energy your cells depend on.
Cortisol, the body’s main stress hormone, plays a central role in this process. When it stays high for too long, it drains your metabolic reserves and interferes with memory formation. Meanwhile, a second hormone called DHEA-S acts as cortisol’s natural counterbalance, helping protect neurons and stabilize brain function.
When the ratio between these two hormones tilts toward cortisol, your brain loses its resilience and becomes more vulnerable to aging and degeneration. This hormonal tug-of-war — shaped by stress, diet, and metabolism — has drawn new attention from researchers exploring why some people develop Alzheimer’s while others do not. The latest findings suggest that long-term hormonal imbalance, not just genetics or plaque buildup, could be one of the earliest warning signs of decline.
Understanding this relationship changes how you think about prevention. By strengthening your metabolism, restoring hormonal balance, and reducing chronic stress, you can support your brain’s ability to heal and adapt — long before symptoms appear. The new research provides a roadmap for how to start.
Stress Hormones Tip the Balance Toward Alzheimer’s
A clinical study published in Cureus examined 85 adults in Serbia — 45 with diagnosed Alzheimer’s disease and 40 healthy peers of similar age and sex — to determine how two hormones, cortisol and DHEA-S, relate to brain health.1 Cortisol is your body’s main stress hormone, while DHEA-S (dehydroepiandrosterone sulfate) acts as its built-in counterbalance — a neurosteroid that supports brain resilience and energy metabolism.
Unlike DHEA, which is the fast-acting, active form, DHEA-S is its sulfated storage form that circulates in your blood far longer and provides a more stable picture of long-term stress balance. By focusing on DHEA-S, the researchers could better gauge chronic stress effects on the brain rather than short-term fluctuations. The scientists wanted to know whether Alzheimer’s patients showed measurable differences in these hormones or in their ratio, which indicates how well your body manages prolonged stress.
• People with Alzheimer’s had higher cortisol levels but not lower DHEA-S — Those with Alzheimer’s showed cortisol levels averaging nearly 399 nanomoles per liter (nmol/L) — about 20% higher than healthy adults — yet their DHEA-S concentrations stayed roughly the same.
This imbalance means the stress response remains chronically activated without the brain’s natural protection. When cortisol dominates, neurons experience more inflammation and less regeneration. The study also noted that this skewed balance was strongest among participants aged 65 to 75, suggesting that middle-to-late adulthood is when stress hormones begin exerting their most damaging effects.
• The cortisol-to-DHEA-S ratio proved to be the real warning sign — Although each hormone alone tells part of the story, the researchers emphasized that their ratio — how much cortisol outweighs DHEA-S — offers a clearer window into chronic stress and brain decline.
In Alzheimer’s patients, that ratio climbed steeply, implying that the body’s defense system against cortisol’s toxicity was failing. This finding helps explain why some people with normal cortisol readings still experience cognitive decline: it’s the imbalance, not just the level, that matters.
• Men and women responded differently, revealing hormonal sensitivity — In healthy adults, men had significantly higher DHEA-S levels than women, meaning their brains could have greater protection from chronic stress. But that sex difference disappeared in those with Alzheimer’s.
The disease seemed to override normal hormonal patterns, flattening DHEA-S levels in both sexes. This means that once neurodegeneration begins, your brain’s ability to maintain hormonal balance — one of its self-defense tools — breaks down.
• Age changed the picture again, suggesting a nonlinear hormonal response — When researchers divided participants by age, they noticed that younger Alzheimer’s patients (60 to 65) had higher DHEA-S levels, which dropped sharply in the 66 to 75 group before rising again after age 75.
This unexpected curve points to a possible window of hormonal collapse, where midlife stress overwhelms the body’s compensatory systems. If you’re in this age range and facing chronic stress, that’s when intervention — stress reduction, adequate rest, and metabolic support — could be most protective for your brain.
Cortisol Acts Like an Overzealous Cleanup Crew That Damages What It’s Meant to Protect
Elevated cortisol increases inflammation and oxidative stress — chemical reactions that corrode neurons and disrupt communication between brain cells. It also suppresses the growth of new neurons in your hippocampus, the brain’s memory center, making it harder to store new information.
In contrast, DHEA-S supports neuronal survival, enhances energy metabolism, and shields brain tissue from the harmful effects of excessive cortisol. When cortisol wins this hormonal tug-of-war, brain networks lose their flexibility and begin to deteriorate.
• Why stress and memory loss are so tightly linked — Chronic cortisol elevation interferes with glucose uptake in brain cells, depriving them of the fuel needed to form memories. It also increases amyloid-beta and tau accumulation — the same proteins that define Alzheimer’s pathology.
Meanwhile, DHEA-S helps counter these effects by enhancing insulin sensitivity and calming overactive immune responses in your brain. In simple terms, one hormone burns your mental circuits, the other repairs them.
• A new biological marker for early intervention — Instead of waiting for memory loss or imaging changes, tracking your cortisol-to-DHEA-S ratio could signal early stress damage years before cognitive symptoms arise.
If your cortisol stays high while DHEA-S falls or stagnates, that’s a red flag. Supporting your metabolic health, prioritizing quality sleep, and restoring hormonal balance could help keep your brain’s internal environment stable long before Alzheimer’s develops.
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Lowering Cortisol and Raising Metabolic Energy Could Reverse Brain Decline
In a commentary, bioenergetic researcher Georgi Dinkov analyzed the Cureus study showing that people with Alzheimer’s disease had significantly higher cortisol levels and a skewed cortisol-to-DHEA-S ratio compared to healthy adults.2 He explained that these results validate decades of bioenergetic research linking chronic stress, low metabolism, and neurodegeneration.
Dinkov emphasized that it’s not just elevated cortisol that drives decline — it’s the imbalance between cortisol and protective steroids such as DHEA, testosterone, and progesterone. When this ratio tips toward cortisol dominance, your body remains in a chronic “fight-or-flight” state that accelerates tissue breakdown and cognitive loss.
• Dinkov connected the findings to thyroid-driven metabolic stress — Building on the Cureus data, Dinkov explained that hypothyroidism — a sluggish thyroid that slows metabolic energy production — creates the same hormonal pattern seen in Alzheimer’s patients: high cortisol and suppressed DHEA–S.
When your metabolism slows, your body compensates by ramping up stress hormones to stay alert and energized. But this backfires over time, leading to chronic brain inflammation, poor glucose uptake, and reduced adenosine triphosphate (ATP) production — the energy currency your brain depends on.
• Your cortisol-to-DHEA-S ratio predicts long-term health better than any single hormone — According to Dinkov, this ratio — spotlighted by the Cureus research — is among the strongest predictors of all-cause mortality and neurodegenerative risk. Even when cortisol fluctuates throughout the day, the ratio reveals whether your stress and repair systems are balanced.
Dinkov suggested measuring cortisol and DHEA-S in hair or nails rather than blood, since these tissues reflect long-term hormonal patterns. For anyone trying to gauge chronic stress or cognitive risk, this offers a simple, objective biomarker that’s far more reliable than a one-time blood test.
• Natural compounds help restore hormonal balance and metabolic strength — Dinkov referenced several well-known substances — aspirin, niacinamide (vitamin B3), progesterone, pregnenolone, thyroid support, glycine, and emodin — that help correct the same imbalance observed in the Cureus study. These compounds work by lowering excess cortisol, improving mitochondrial energy output, and supporting the production of protective hormones.
Niacinamide, for instance, increases NAD+, which fuels cellular repair, while aspirin dampens inflammation and cortisol overproduction. Used together, these tools shift your body back into a “rest-and-repair” mode rather than the constant stress chemistry that drives brain aging.
• DHEA acts as a built-in cortisol regulator — Dinkov explained one of the key ways DHEA helps keep cortisol in check: it blocks the enzyme that turns inactive cortisol back “on” and boosts the one that clears excess cortisol from your body. This dual action makes DHEA a natural cortisol buffer that prevents the overactivation of stress pathways.
In other words, DHEA gives your brain a biochemical “cooling system,” stopping cortisol from overheating your neurons. Supporting DHEA through thyroid health, nutrition, and targeted supplementation helps restore this essential balance.
• Stress is a symptom of low energy, not just emotional strain — Dinkov described how the elevated cortisol levels observed in the Cureus Alzheimer’s cohort represent a deeper issue: energy failure. When your cells don’t make enough ATP — whether from poor thyroid output, nutrient deficiencies, or aging — they turn to cortisol to compensate.
The hormone breaks down tissue to release fuel, but that process worsens energy depletion over time. This self-reinforcing loop explains why chronic stress feels endless: it’s a metabolic, not psychological, trap. Dinkov concluded that maintaining a low cortisol-to-DHEA-S ratio protects more than memory — it sustains whole-body resilience.
People who keep this ratio balanced experience better sleep, stable mood, and slower biological aging. His message is practical: by restoring thyroid function, eating enough to prevent energy deficits, and lowering chronic inflammation, you directly influence the biochemical environment that determines whether your brain decays or endures.
Rebuild Your Energy System to Lower Cortisol and Protect Your Brain
If you wake up tired, crash midafternoon, or feel wired when you should be asleep, your body’s stress chemistry has taken over. The Cureus study3 and Dinkov’s review4 both point to the same conclusion: your brain suffers when your cells can’t make enough energy.
To fix that, you have to restore steady fuel, retrain your stress response, and help your body recognize that it’s no longer in survival mode. Here’s how to bring your hormones — and your energy — back into balance:
1. Feed your metabolism the fuel it’s been missing — Cutting carbs keeps your body trapped in a constant stress loop because cortisol spikes whenever blood sugar drops too low. Break that pattern by eating enough healthy carbohydrates — around 250 grams daily — to give your mitochondria a steady energy supply.
Start with gentle foods like fruit and white rice. When your digestion feels stable (no bloating or irregularity), add cooked root vegetables, then more vegetables, legumes, and well-tolerated whole grains. Once your body trusts it’s being fed regularly, cortisol naturally declines, and your energy and focus stabilize.
2. Move in ways that restore instead of deplete — Overdoing endurance exercise or high-intensity intervals keeps your body in fight-or-flight mode long after the workout ends. Cortisol stays elevated, recovery slows, and sleep suffers.
Replace long, punishing sessions with physical activities that build energy rather than drain it — strength training, walking outdoors, dancing, or swimming at an easy pace. Use how you feel afterward as your guide: if you finish feeling grounded and calm, you’ve helped your hormones, not hurt them.
3. Train your nervous system to shift out of stress — Your breath is the fastest lever you have to quiet cortisol and activate your parasympathetic, or “rest and digest,” system. Try rhythmic breathing patterns like 4-7-8 or 4-8 breathing — inhaling for four seconds, holding briefly, and exhaling slowly for seven to eight seconds.
The extended exhale stimulates your vagus nerve, lowering heart rate and cortisol while signaling safety to every organ. Practice before bed, after meals, or whenever tension rises. Over time, your body learns that it no longer needs to live in emergency mode.
4. Rebuild your circadian rhythm through light and sleep — Cortisol follows your light exposure, not your alarm clock. Get outside within an hour of waking to anchor your body’s circadian rhythm, and dim screens and overhead lighting at night so melatonin can rise naturally.
Keep your bedtime and wake-up times consistent — even on weekends — to lock in hormonal balance. Deep, regular sleep clears stress hormones, strengthens memory, and repairs brain tissue. If you’re dragging through the day, fix your light and sleep first instead of relying on caffeine.
5. Use natural progesterone to quiet the cortisol surge — Bioidentical progesterone acts as your body’s built-in cortisol brake, restoring calm where chronic stress has hijacked balance. Unlike synthetic versions, natural progesterone fits perfectly into your body’s own receptor system, lowering cortisol’s overstimulation and supporting deep rest.
FAQs About Cortisol and Alzheimer’s Disease
Q: What did the new Alzheimer’s study reveal about cortisol and DHEA-S?
A: Researchers found that people with Alzheimer’s disease had cortisol levels roughly 20% higher than healthy adults, while their DHEA-S levels stayed about the same. This created a skewed cortisol-to-DHEA-S ratio — meaning stress hormones were overpowering the brain’s natural defenses. That imbalance, not just genetics or amyloid buildup, appears to drive the early stages of brain decline.
Q: How are DHEA and DHEA-S different?
A: DHEA is the fast-acting form of the hormone, while DHEA-S is the stable, long-lasting form stored in your blood. Because DHEA-S changes slowly, it’s a better measure of long-term stress and brain resilience. It also acts as a neurosteroid, helping neurons resist inflammation and oxidative damage while buffering cortisol’s harmful effects.
Q: What did Georgi Dinkov’s analysis add to this research?
A: Dinkov explained that the Cureus study confirms a broader principle: high cortisol and low metabolic energy often go hand in hand. He connected these hormone shifts to thyroid sluggishness, nutrient depletion, and aging — all of which drain cellular energy and raise stress chemistry. He also noted that maintaining a low cortisol-to-DHEA-S ratio predicts not just better memory but longer life and greater overall resilience.
Q: What practical steps help lower cortisol and restore hormonal balance?
A: To calm your stress system, start by fueling your metabolism. Eat enough healthy carbohydrates — about 250 grams per day — to keep blood sugar stable. Cut back on overtraining, use rhythmic breathing to activate your vagus nerve, and rebuild your circadian rhythm by getting morning sunlight and sleeping on a consistent schedule. These changes lower cortisol naturally while improving energy and mental clarity.
Q: How does progesterone fit into this picture?
A: Natural progesterone acts as a built-in cortisol blocker. Your body recognizes it as a calming, balancing hormone that reduces overstimulation, helps you sleep deeply, and stabilizes mood. Natural progesterone effectively blocks cortisol by reducing blood concentrations, helping restore hormonal harmony, protecting your brain and body from the long-term effects of stress.
The Four Hormones Most Adults Need More Of
Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2023/12/03/four-hormones-most-adults-need-more-of.aspx
The original Mercola article may not remain on the original site, but I will endeavor to keep it on this site as long as I deem it to be appropriate.
Analysis by Dr. Joseph Mercola December 03, 2023
STORY AT-A-GLANCE
- Four hormones most adults can benefit from are progesterone, thyroid hormone T3, DHEA and pregnenolone
- Around the ages of 11 and 12, right before puberty, the hormonal profiles of boys and girls are relatively similar. They produce about the same amounts of pregnenolone and progesterone. This is also the time when thyroid hormone levels are the highest they’ll ever be, and it’s the time in a person’s life cycle when their mortality is the lowest. Most supplementation recommendations are based on these prepubescent levels
- To optimize bioavailability, take T3, DHEA and/or pregnenolone orally, after dissolving them in a long-chain fat (14 carbons or more) such as ghee or butter
- The normal daily output of DHEA by the adrenal gland is about 20 to 50 milligrams (mg), so for most people, the max DHEA dose would be 50 mg, ideally split into several smaller doses. Human studies have shown that once you take more than 50 mg of DHEA per day, you begin to increase estrogen biomarkers. Best to start at 5-10 mg.
- As a general recommendation, I recommend taking 30 to 50 mg of bioidentical progesterone per a day, taken in the evening before bed, as it can promote sleep. The same dose (30 to 50 mg a day) is recommended for pregnenolone. This is the physiological dose, meaning it’s what you need for full replenishment, assuming you’re producing nothing
In this interview, repeat guest Georgi Dinkov and I discuss the four hormones most adults need more of if they want to optimize their health. In my introduction I mention that we will review the benefits and mechanisms of action of carbon dioxide (CO2), but that will be covered in Part 2 of this interview that will be posted in the next few weeks.
As for hormones, if you’re optimally healthy, hormone replacement therapy (HRT) is unnecessary, as your body will make whatever hormones you need. The problem is that very few people, including me, enjoy truly optimal health.
We live in a very polluted world, so “optimal health” is a high bar for all of us. I take four hormones that I believe most adults can benefit from: Progesterone, thyroid hormone T3, DHEA and pregnenolone.
Three of these, progesterone, DHEA and pregnenolone are available over-the-counter. Thyroid hormones, however, require a doctor’s prescription. You also need to get routine blood tests done (typically two to four times a year) to make sure your thyroid hormones are maintained at optimal levels. Overtreatment can result in hyperthyroid symptoms, which you clearly want to avoid.
How Hormones Impact Health Span and Life Span
As noted by Dinkov, around the ages of 11 and 12, right before puberty, the hormonal profiles of boys and girls are relatively similar, and they produce about the same amounts of pregnenolone and progesterone.
This is also the time when thyroid hormone levels are the highest they’ll ever be, and it’s the time in a person’s life cycle when their mortality is the lowest. Once puberty strikes, adrenal activity increases. In fact, the old name for puberty was adrenarchy, which tells you that adrenal activity is driving the process.
At this time, boys start producing more testosterone and girls progesterone (depending on where they are in the menstrual cycle). Interestingly, many studies have shown that the later puberty starts, the longer the lifespan and health span of both sexes. Conversely, the earlier the onset of puberty, the shorter the lifespan and the more prone to diseases the individual will be.
“After puberty starts and until the late 20s, people are remarkably resilient to stress,” Dinkov notes. “In fact, stress often seems stimulating for them. This seems to change drastically after they hit 30, and especially after 35. It’s basically a very steep decline.
And if you look at the way the hormonal profile changes, you’ll see that whenever young, healthy people are exposed to stress, there’s a spike in cortisol release, followed closely by a spike of pregnenolone and DHEA release for males, and pregnenolone, progesterone and DHEA release for females.
That delayed release of these secondary hormones drop off a cliff after the age of about 35. The ranges for pregnenolone, progesterone and DHEA, and even testosterone, change depending on what age group you fall into, but the range for cortisol doesn’t change.
So, throughout your lifetime, unless you’re critically ill, in which case cortisol drops, or you have Addison disease, which is full on adrenal failure, your cortisol levels do not decline, and that’s what keeps you alive because, if you have adrenal failure, unless you take cortisol shots you will die from hypoglycemia or Addison’s disease. So, it’s lethal.
Cortisol is really a life-saving hormone. It’s proinflammatory, but its primary purpose is to keep blood sugar from dropping too low, because your brain runs predominantly on glucose. So, basically, after the age of 35, cortisol stays the same.
It’s a catabolic hormone. It can shred your muscles, soft tissue, bone, you name it. There’s no organ that is immune to the effects of cortisol. There is only one that is somewhat resilient, and it’s the heart. And the reason the heart is so resilient in both genders is because in males, the heart contains a very large amount of testosterone, and in females it contains very large amounts of progesterone.
Both of these happen to be glucocorticoid antagonists. So they’re protecting this vital muscle … but all the other tissues can be shredded and they’re considered basically nonessential. So, after the age of 35, you have a stable supply of a catabolic hormone and then a rapidly declining supply of pregnenolone, progesterone and DHEA, all three of which have antiglucocorticoid effects.”
All of that said, if you’re taking progesterone, you don’t need to worry about the DHEA converting to estrogenic substances because progesterone will block that conversion. Even if there is conversion, progesterone is an antagonist at the estrogen receptors so it will directly block the estrogen as well. Pregnenolone has similar effects. It’s a milder aromatase inhibitor than progesterone, but it’s still quite good at preventing the uptake of estrogen into the cell.
Cortisol-to-DHEA Ratio Is a Good Predictor of Life Span
One of the take-homes from the above is that when you’re young, before puberty sets in, you have high production of T3 thyroid hormone, cortisol and anti-cortisol steroids. After age 35, there’s a gradual decline of thyroid function and a rapid decline in the synthesis and release of the anti-cortisol hormones, some of which also happen to be anti-estrogenic.
As a result, you enter a state of relative glucocorticoid and estrogen excess, both of which have detrimental effects on health. Dinkov explains:
“The state of glucocorticoid excess is not very well known. It’s easily measurable though by the ratio of cortisol to DHEA, or cortisol to progesterone, or cortisol to pregnenolone. Studies demonstrate that the cortisol to DHEA ratio is the best predictor we have for how long you’re going to live and for any diseases that you’re going to develop throughout your lifetime.”
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DHEA Influences Your Immune Function
One of the reasons for this is because DHEA is an immune booster, and your immune system is your first line of defense against both acute and chronic diseases, including cancer. And the amount of DHEA produced is about the same in both sexes, regardless of age. Dinkov suspects an ideal ratio of cortisol to DHEA is 0-to-3 or lower.
As for DHEA by itself, he recommends aiming for a level in the upper 50th percentile for the upper range of a 20-year-old, which is around 600 nanograms per deciliter (ng/dL). So, ideally, if you’re older than 35, you’d want your DHEA to be somewhere between 300 and 600 ng/dL.
As for the daily dosage, the normal daily output of DHEA by the adrenal gland is about 10 milligrams (mg), so for most people, the max DHEA dose would be 5-10 mg and mixed with a long-chain fat. According to Dinkov, human studies have shown that once you take more than 10 mg of DHEA per day, you begin to increase estrogen biomarkers, which is something you don’t want.
“Anything less than [10 mg], which happens to be a physiological dose, doesn’t really cause that much of a problem, but I would still take it with progesterone because blood levels are not always indicative of tissue levels,” Dinkov says.
“In fact, [DHEA] is not always reflected on the blood test … If you look at the studies, they show you that cells have a very high uptake of pregnenolone and DHEA. They accumulate them at levels 100 times higher than what they are in the bloodstream. So if you’re very DHEA deficient, it will take a while to fill up your reserves and then for the extra to spill over. About six months.
There’s a study with Italian women. They took 10 mg for a full year. Eventually that restored their levels back to normal, but not until the six-month mark did they see significant change. So it really depends on how deficient you are, for how long you’ve been deficient, and the state of your adrenal gland.
Another study demonstrated that the DHEA starts working immediately. You don’t see it in the blood test, but they started measuring downstream metabolites of DHEA and found that taking just 10 mg of DHEA drastically increased the metabolites of the dihydrotestosterone such as 3-alpha androstane diol and metabolites of testosterone, such as testosterone glucoronate and sulfate.
So, DHEA starts working immediately and converting to downstream hormones, but it’s going to take a while to see that in the biomarkers that are usually measured, which is DHEA and DHEA sulfate. What they really should be doing is measure all of the other things that DHA can convert into.
And some of those things are estrogens. Chances are, at least based on studies, that either prolactin or estrone will rise if you’re taking too high of a dose long before there will be changes in the blood levels of DHEA or DHEA sulfate.”
Caveats and Warnings
There are a few important caveats here. Taking too high a dose of DHEA can cause unwanted hair growth in women, and breast growth in men,1 so be sure to monitor your symptoms. DHEA is also banned in sports. It’s classified as a doping agent by the World Anti-Doping Agency, so athletes must take their competitive status into account before taking supplemental DHEA.
Also, never take DHEA without progesterone. They need to be taken together. Another point to optimize the therapy and not derail it is that if you take T3, DHEA and/or pregnenolone orally, you need to dissolve them in a long-chain fat (14 carbons or more) first.
If you don’t do that, they’ll be metabolized by your liver, which significantly lowers their effectiveness. According to Dinkov, the bioavailability of oral hormones can be as low as 10%. Dissolving the supplements in a little ghee or butter will bypass liver metabolism and allow you to get the most out of your supplements.
Olive oil is also a long-chain fat, but I don’t recommend it in this case, as it can have 20% linoleic acid (LA) and a flavor that many don’t like. According to Dinkov, at least one study has demonstrated that LA binds directly to estrogen receptors and acts like estrogen.
So, LA not merely promotes the effects of estrogen but also acts as an estrogen directly. Since estrogen is a potent carcinogen, you want to avoid things with estrogenic activity.
Progesterone Works Best With Vitamin E
Progesterone, meanwhile, needs to be mixed into vitamin E for optimal bioavailability. Health Natura sells a progesterone in vitamin E product. Alternatively, you can make your own by dissolving pure USP progesterone powder in one capsule of a high-quality vitamin E. The difference in bioavailability between taking progesterone orally without vitamin E and taking it with vitamin E is 45 minutes versus 48 hours.
Another good reason for taking progesterone with vitamin E is because it binds to red blood cells, which allows the progesterone to be carried throughout your body and be distributed to where it’s needed the most. What’s more, Dinkov cites recent research showing that when you dissolve a substance in vitamin E, it specifically targets sites with the highest inflammation.
Other Important Benefits of Vitamin E
Another important benefit of vitamin E is that it prevents LA stored in your tissues from being oxidized into toxic byproducts. Since most people are walking around with LA stores that are 10 times higher than normal, and since excess LA is likely one of the primary contributors to chronic disease, it can be a good idea to take vitamin E regularly until you get your LA down to healthy levels, which may take up to six years for most people.
Vitamin E can almost miraculously prevent most of the damage done by LA. It can also reverse or prevent many of the issues associated with excess estrogen. This is important because LA has remarkable parallels to excess estrogen in terms of its metabolic and anti-health effects.
When you eat excess PUFA or LA, you increase your body’s production of estrogen. So, when you increase LA, estrogen levels go up — and that’s not a good thing. Both LA and estrogen interestingly increase the flow of calcium from outside the cell to inside because the concentration of calcium outside as well is 50 times higher than inside. So, the excess as LA will cause the influx of calcium inside the cell, which causes nitric oxide and superoxide to increase inside the cell.
Nitric oxide and superoxide combine almost instantaneously to form a very pernicious reactive nitrogen species called peroxynitrite, which causes pervasive damage to tissues in your body.
Both LA and estrogen also increase a potentially dangerous process in your body called lipolysis, which is simply the liberation of fatty acids from your fat cells into your bloodstream where they are mobilized. This then increases the oxidation of LA, which is precisely what you want to avoid as ideally you want to keep LA in your fat cells until they metabolize it with peroxisomes.
Fortunately, vitamin E can also help neutralize this damaging effect of LA. Vitamin E also directly inhibits the activity of an enzyme called aromatase. This is an enzyme that converts the male hormones like testosterone and DHEA into estrogens.
Even better, it serves as an estrogen antagonist, meaning it binds to the estrogen receptor to block it from binding to estrogen. This dramatically lowers the damage from excess estrogen.
Vitamin E works very similarly to the drug tamoxifen, which is used to treat estrogen receptor-positive breast cancers. For these reasons, I firmly believe nearly everyone needs to be getting vitamin E in their diet. However, due to the high LA burden, very few people can get enough vitamin E from their diet to suppress this oxidative destruction unless they’re supplementing with vitamin E.
The good news is that since the supplementation is short term, you’re not going to need it the rest of your life. If you can keep your LA intake to below 5 grams a day for three years, it’s likely you may not even need it at all, or at most, only a few times a month.
However, if for whatever reason, during this time, or when the LA in your tissues are low or normal, and you go out and binge on a meal that’s very high in LA, I would strongly recommend taking a vitamin E capsule to protect yourself from this exposure.
Vitamin E also protects against free radical damage and the normal effects of aging. It’s particularly important for brain health, and studies have found it can help delay the loss of cognitive function in people with Alzheimer’s disease by preventing cell membrane damage and neuronal death.2
How to Pick a Good Vitamin E Supplement
Most vitamin E supplements are synthetic, and you want to steer clear of those. Studies have demonstrated that synthetic vitamin E has the opposite effect of natural vitamin E, such as increasing the risk of certain cancers rather than lowering it, for example. So, it’s important to make sure you’re getting a natural version.
Synthetic vitamin E is called alpha tocopherol acetate. The acetate indicates that it’s synthetic. Next, you need to pay attention to the orientation of the optical isomer. Most vitamin supplements are racemic, or they have left- and right-hand isomers. This is a problem as most biological molecules have optical isomers that are right-handed.
They’re usually called D and L isomers, which stands for right and left. When you have both left and right isomers present, it’s called racemic. Biologically, there’s usually only one optical isomer that works well, and with vitamin E it is the D isomer that works in your body, while the L isomer is useless. Yet in synthetic supplements, 50% of the vitamin E in the supplement is the useless L isomer.
To make matters even worse, many synthetic versions use an ester of vitamin E, which only has about 50% of the activity of the natural product. So, the total activity of many vitamin E supplements is reduced by 75%.
So, the first step in identifying healthy good vitamin E supplements is to make sure you’re getting real vitamin E and not synthetic. What you’re looking for is “d alpha tocopherol.” This is the pure D isomer, which is what your body can use.
Many vitamin E brands will use vitamin E from sunflower oil, which has a very high percentage of LA. However, the LA in the capsule is an insignificant amount, probably less than 50 or 100 mg, so in this case it’s not a problem. Your goal is to keep LA intake under 5,000 mg, and even better under 2,500 mg, so it really won’t negatively impact your LA intake at all.
As for dose, you don’t need more than 100 mg a day. There are also other vitamin E isomers, and you want the complete spectrum of tocotrienols, specifically the beta, gamma, and delta types of vitamin E, in the effective D isomer. It’s important to get this right, which is why I’m going into this much detail.
Most People Can Benefit From Bioidentical Progesterone
So, to tie up the discussion about progesterone, bioidentical progesterone (not synthetic progestin) is probably the most important hormone that most adults need. Conversely, I believe estrogen — including bioidentical estrogen — should never be used, as estrogen is carcinogenic.
As noted by Dinkov, virtually all cancers respond to hormones and estrogen is a primary growth factor in all of them. So, there’s really no such thing as a nonendocrine cancer. To learn more about this, see our previous interview, where we dove deeper into the hazards of estrogen.
Unfortunately, most people who use progesterone use it transdermally, which could be problematic. As explained by Dinkov, your skin expresses high levels of 5-alpha reductase enzyme, which causes a significant portion of the progesterone you’re taking to be irreversibly converted primarily into allopregnanolone and cannot be converted back into progesterone.
If you’re taking it orally with vitamin E as the solvent, a significant portion will be non-metabolized, that non-metabolized progesterone has potent pro-thyroid effects. It’s also a thermogenic steroid. It induces uncoupling, so you’ll be producing more heat, which is one of the effects of taking T3. While not as potent as taking T3, it can raise your metabolic rate by about 10%.
Progesterone also blocks cortisol and helps protect against excess cortisol production, but not to the point of causing cortisol deficiency (Addison disease), and it helps deactivate adrenaline.
“There are human studies demonstrating that you administer progesterone, even in its nonoptimal form — such as just the powder without the long-chain fatty acids and definitely without the tocopherols — even in that form, 100 to 200 milligrams orally.
A single dose is sufficient to drop cortisol and adrenaline by about 60%. As a side effect of that, the blood pressure also dropped in both sexes,” Dinkov says. “So, we know that progesterone has a very potent antistress effect by acting specifically on the two sides of the stress system, cortisol and adrenaline.
One of the explanations is that progesterone has shown some ability to directly activate the alpha receptors, which are negative feedback. In other words, if you activate the alpha adrenal receptor, you basically send in the signal that there’s too much adrenaline, so the body will produce less adrenaline …”
The dose of bioidentical progesterone I recommend is 30 to 50 mg a day (again, mixed with a long-chain fat), taken in the evening before bed, as it can promote sleepiness. The same dose (30 to 50 mg a day) is recommended for pregnenolone. This is the physiological dose, meaning it’s what you need for full replenishment, assuming you’re producing nothing.
Important Caveat for Menstruating Women
Women who still menstruate need to be careful with the timing of their progesterone supplementation. Progesterone is crucial for successful pregnancy, and you can severely inhibit your ability to get pregnant if you take it at the wrong time. (During pregnancy, progesterone actually skyrockets. In the third trimester, women produce about 600 mg a day.)
If your menses are regular, start taking the progesterone on the 14th day after your menstrual flow begins, and take it for 14 days straight (until cycle day 27). If your cycles are short, start on day 12 and continue for 14 days. Always take the progesterone for the full 14 days even if your menses begin before the 14 days are over. Start the next progesterone 14 days after the flow began.3
There’s no toxicity to progesterone, unlike estrogen and testosterone, neither of which I recommend. Progesterone, T3, DHEA and pregnenolone are the only hormones you really need. Supplementing progesterone also will not lower your natural production, so you don’t need to be concerned about that. In fact, it enhances your natural production.
Thyroid Hormone Supplementation
When it comes to your thyroid, most people only need T3. That said, desiccated thyroid contains both T3 and T4 and can be a good option for some. Here, unless you’re treating a specific thyroid problem, the generally recommended dose is 10 micrograms two to three times a day. Dinkov comments:
“The thyroid gland produces about 100 micrograms in a healthy person — 100 micrograms of T3 over 24-hour period. If you take more than 25 micrograms, even that is a very high dose because it has such a potent thermogenic effect, and in higher doses can be catabolic.
The body has deiodinase enzymes, and they very quickly convert the excess T3 into something called T2 and even T1 … So, in other words, you’re going to be wasting most of it. Interestingly, the same type of enzymes, T3 deactivating, are highly overexpressed in cancer cells, and cancer cells just happen to be very hypometabolic, as we’ve discussed previously.
So the thyroid gland produces T3 and T4 in a ratio of about 1 to 4 in favor of T4. T4 is actually a prohormone, it by itself does not have a very high activity directly at the thyroid receptors T3. So, it circulates and about 80% of it in the liver, in a healthy person, should get converted to T3. The other 20% can get converted to T3 peripherally, or if the dosage of T4 is too high, the excess very quickly gets converted to something called reverse T3.
This is a very dangerous state because reverse T3 acts as a thyroid hormone antagonist … Most doctors don’t take these things into account, so if they prescribe you, let’s say, 100 or 200 micrograms T4 daily. You better be praying that this will get properly converted because if it doesn’t, and gets converted to reverse T3, you’ll end up in a more hypothyroid state than if you did not take the T4 at all …
T4 is almost never a good option by itself unless the person is very young. But even then, if a person is hypothyroid, that by definition already means that the liver will be burdened, because one of the primary functions of the liver is the detox mechanisms and one of the primary things that liver detoxifies are polyunsaturated fats and estrogens.
But the detoxification mechanisms themselves depend on thyroid function. So hypothyroid means sluggish liver by definition. So, if you give a hypothyroid person T4 only, especially if the dose is higher, you’re asking for trouble. Some of that will get converted to reverse T3.”