It’s hard to make it through the week without hearing someone talking about Ozempic or Wegovy for managing blood sugar and achieving weight loss. In some ways, this is great—we are finally having conversations about the previously taboo topics of weight management and obesity.
Tag: hormones
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How Low Can LDL Cholesterol Go on PCSK9 Inhibitors? | NutritionFacts.org
People with genetic mutations that leave them with an LDL cholesterol of 30 mg/dL live exceptionally long lives. Can we duplicate that effect with drugs?
Data extrapolated from large cholesterol-lowering trials using statin drugs suggest that the incidence of cardiovascular events like heart attacks would approach zero if LDL cholesterol could be forced down below 60 mg/dL for first-time prevention and around 30 mg/dL for those trying to prevent another one. But is lower actually better? And is it even safe to have LDL cholesterol levels that low?
We didn’t know until PCSK9 inhibitors were invented. Are PCSK9 Inhibitors for LDL Cholesterol Safe and Effective? I explore that issue in my video of the same name. PCSK9 is a gene that mutated to give people such low LDL cholesterol, and that’s how Big Pharma thought of trying to cripple PCSK9 with drugs. After a heart attack, intensive lowering of an individual’s LDL cholesterol beyond a target of 70 mg/dL does seem to work better than more moderate lowering. There were fewer cardiovascular deaths, heart attacks, or strokes at an LDL less than 30 mg/dL compared with 70 mg/dL or higher, and even compared to less than 70 mg/dL. There is a consistent risk reduction even when starting as low as an average of 63 mg/dL, and pushing LDL down to 21 mg/dL, remarkably, showed “no observed offsetting” of adverse side effects.
Maybe that shouldn’t be so surprising, since that’s about the level at which we start life. And there’s another type of genetic mutation that leaves people with LDL levels of about 30 mg/dL their whole lives, and they are known to have an exceptionally long life expectancy. So, where did we get this idea that cholesterol could fall too low?
The common claim that lowering cholesterol can be dangerous due to depletion of cell cholesterol is unsupported by evidence and does not consider the exquisite balancing mechanisms our body uses. After all, that’s how we evolved. Until recently, most of us used to have LDL levels around 50 mg/dL, so that’s pretty normal for the human species. The absence of evidence that low or lowered cholesterol levels are somehow bad for us contrasts with the overwhelming evidence that cholesterol reduction decreases risk for coronary artery disease, our number one killer.
What about hormone production, though? Since the body needs cholesterol for the synthesis of steroid hormones—like adrenal hormones and sex hormones—there’s a concern that there wouldn’t be enough. You don’t know, though, until you put it to the test. For decades, we’ve known that women on cholesterol-lowering drugs don’t have a problem with estrogen production and that lowering cholesterol doesn’t affect adrenal gland function. As well, it doesn’t impair testicular function in terms of causing testosterone levels to fall below normal. If anything, statin drugs can improve erectile function in men, which is what you’d expect from lowering cholesterol. But you’ll notice these studies only looked at lowering LDL to 70 mg/dL or below. What about really low LDL?
On PCSK9 inhibitors, you can get most people under an LDL of 40 mg/dL and some under 15 mg/dL! And there is no evidence that adrenal, ovarian, or testicular hormone production is impaired, even in patients with LDL levels below 15 mg/dL. The risk of heart attacks falls in a straight line as LDL gets lower and lower, even below 10 mg/dL, for example, without apparent safety concerns, but that’s over the duration of exposure to these drugs. The longest follow-up to date of those whose LDL, by way of using multiple medications, was kept less than 30 mg/dL is six years.
Now, we can take comfort in the fact that those with extreme PCSK9 mutations, leading to a lifelong reduction in levels of LDL to under 20 mg/dL their whole lives, remain healthy and have healthy kids. Cholesterol-affecting mutations are what cause the so-called “longevity syndromes,” but that doesn’t necessarily mean the drugs are safe. The bottom line is we should try to get our LDL cholesterol down as low as we can, but much longer follow-up data are necessary anytime a new class of drugs is introduced. So far, so good, but we’ve only been following the data for about 10 years. For example, we didn’t know statins increased diabetes risk until decades after they were approved and millions had been exposed. Also worth noting: PCSK9 inhibitors cost about $14,000 a year.
Doctor’s Note
How can we decrease cholesterol with diet? See Trans Fat, Saturated Fat, and Cholesterol: Tolerable Upper Intake of Zero.
For more on statin drugs, see the related posts below.
Michael Greger M.D. FACLM
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Feeling Foggy or Forgetful? How Menopause Changes The Brain
During the menopausal transition, gray matter, the brain tissue responsible for memory, focus, and decision-making, tends to shrink in certain regions, including the frontal and temporal cortices and the hippocampus. This helps explain why so many women describe a mental “fog” or trouble concentrating.
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Cancer Rates Are 82% Higher For Younger Women—Here’s Why
Despite these troubling trends, there’s positive news: overall cancer survival rates continue to improve, thanks to advances in early detection, targeted therapies, and lifestyle interventions. The U.S. cancer mortality rate has dropped by 34% since 1991, largely due to declines in smoking rates and better screening practices.
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How To Know If You’re Reliant On Melatonin & What To Do
Create a nighttime “power down” ritual: Your wind down routine can involve relaxing activities that don’t involve a screen, like journaling, reading, or listening to an audiobook. “A nighttime ritual helps your body know it’s time to go to bed,” Mysore notes. That said, she recommends against eating, drinking, or exercising too close to bedtime, as these things can be counterproductive.
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Move This Much Each Day To Beat Hormonal Brain Fog, Study Finds
If you’ve ever blamed your hormones for brain fog or slower thinking, you’re far from alone. Many women report feeling less focused or sharp during certain phases of their menstrual cycle. But new research published in Sports Medicine challenges that long-held assumption.
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Is Your Cortisol High? Here's How To Test Your Levels From Home In Minutes
Is your cortisol really high?
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This Free Technique Could Enhance Brain Health & Response Time, Study Finds
Lights, cells, action!
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Female Alzheimer’s Risk: Early Menopause, Hormones & More
As Lisa Mosconi, Ph.D., neuroscientist, nutritionist, and associate director of the Alzheimer’s Prevention Clinic at Weill Cornell Medical College, previously explained in a mindbodygreen podcast episode, reproductive hormones help protect our brains from the development of amyloid plaques associated with Alzheimer’s disease. As women hit menopause, their estrogen levels plummet, leaving their brains more susceptible to dementia.
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This New Wearable Helps Minimize Mood Swings & Pain For Women
It’s time to stop pushing through your cycle.
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Can’t Sleep Before Your Period? Here’s Why — & What Helps
You know that week before your period when you’re inexplicably exhausted, yet somehow can’t stay asleep? When you’re snapping at everyone and can’t figure out why? Turns out, your hormones aren’t just messing with your mood—they’re quietly impacting your sleep, too.
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The Sneaky Link Between Vitamin D & PMS Symptoms
Considering clinical vitamin D insufficiency persists in almost half of the U.S., population (41 percent1
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Sleep Disorders Show Up Differently In Women, Says An M.D.
One way to do so, Afolabi-Brown says, is to build breaks into your schedule (like, actual breaks). “We have to create pauses in the day—and we have to do so intentionally,” she says. “The day is not going to give that to us.” In addition to taking breathers throughout the day, carving out time for a consistent wind-down routine, or “buffer zone,” before bed is key.
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If kids are on the table someday, it's prime time to get into these habits.
If kids are on the table someday, it’s prime time to get into these habits.
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Bioidentical vs. Synthetic HRT: What Experts Want Every Woman To Know
Experts break it down.
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4 Hormonal Dementia Risk Factors That Directly Impact Women
“In particular, they literally push our neurons to bring glucose to make energy. So if your hormones are high, your brain energy is high. But then what happens to testosterone is that it doesn’t quite decline that much over time, whereas for women, estrogens pretty much plummet when women go through menopause,” Mosconi shares.
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How To Know If You’re Reliant On Melatonin & What To Do
Create a nighttime “power down” ritual: Your wind down routine can involve relaxing activities that don’t involve a screen, like journaling, reading, or listening to an audiobook. “A nighttime ritual helps your body know it’s time to go to bed,” Mysore notes. That said, she recommends against eating, drinking, or exercising too close to bedtime, as these things can be counterproductive.
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This Often Overlooked Nutrient Helps Balance Hormones & Lifts Mood
Are you getting enough of this hormone-friendly nutrient?
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Eating to Downregulate a Gene for Metastatic Cancer | NutritionFacts.org
Women with breast cancer should include the “liberal culinary use of cruciferous vegetables.”
Both the Women’s Intervention Nutrition Study and the Women’s Health Initiative study showed that women randomized to a lower-fat diet enjoyed improved breast cancer survival. However, in the Women’s Healthy Eating and Living Study, women with breast cancer were also randomized to drop their fat intake down to 15 to 20 percent of calories, yet there was no difference in breast cancer relapse or death after seven years.
Any time there’s an unexpected result, you must question whether the participants actually followed through with study instructions. For instance, if you randomized people to stop smoking and they ended up with the same lung cancer rates as those in the group who weren’t instructed to quit, one likely explanation is that the group told to stop smoking didn’t actually stop. In the Women’s Healthy Eating and Living Study, both the dietary intervention group and the control group started out at about 30 percent of calories from fat. Then, the diet group was told to lower their fat intake to 15 to 20 percent of calories. By the end of the study, they had in fact gone from 28.5 percent fat to 28.9 percent fat, as you can see below and at 1:16 in my video The Food That Can Downregulate a Metastatic Cancer Gene. They didn’t even reduce their fat intake. No wonder they didn’t experience any breast cancer benefit.
When you put together all the trials on the effect of lower-fat diets on breast cancer survival, even including that flawed study, you see a reduced risk of breast cancer relapse and a reduced risk of death. In conclusion, going on a low-fat diet after a breast cancer diagnosis “can improve breast cancer survival by reducing the risk of recurrence.” We may now know why: by targeting metastasis-initiating cancer cells through the fat receptor CD36.
We know that the cancer-spreading receptor is upregulated by saturated fat. Is there anything in our diet that can downregulate it? Broccoli.
Broccoli appears to decrease CD36 expression by as much as 35 percent (in mice). Of all fruits and vegetables, cruciferous vegetables like broccoli were the only ones associated with significantly less total risk of cancer and not just getting cancer in the first place, as you can see here and at 2:19 in my video.
Those with bladder cancer who eat broccoli also appear to live longer than those who don’t, and those with lung cancer who eat more cruciferous veggies appear to survive longer, too.
For example, as you can see below and at 2:45 in my video, one year out, about 75 percent of lung cancer patients eating more than one serving of cruciferous vegetables a day were still alive (the top line in red), whereas, by then, most who had been getting less than half a serving a day had already died from their cancer (the bottom line in green).
Ovarian cancer, too. Intake of cruciferous vegetables “significantly favored survival,” whereas “a survival disadvantage was shown for meats.” Milk also appeared to double the risk of dying. Below and at 3:21 in my video are the survival graphs. Eight years out, about 40 percent of ovarian cancer patients who averaged meat or milk every day were deceased (the boldest line, on the bottom), compared to only about 20 percent who had meat or milk only a few times a week at most (the faintest line, on the top).
Now, it could be that the fat and cholesterol in meat increased circulating estrogen levels, or it could be because of meat’s growth hormones or all its carcinogens. And galactose, the sugar naturally found in milk, may be directly toxic to the ovary. Dairy has all its hormones, too. However, the lowering of risk with broccoli and the increasing of risk with meat and dairy are also consistent with the CD36 mechanism of cancer spread.
Researchers put it to the test in patients with advanced pancreatic cancer who were given pulverized broccoli sprouts or a placebo. The average death rate was lower in the broccoli sprout group compared to the placebo group. After a month, 18 percent of the placebo group had died, but none in the broccoli group. By three months, another 25 percent of the placebo group had died, but still not a single death in the broccoli group. And by six months, 43 percent of the remaining patients in the placebo group were deceased, along with the first 25 percent of the broccoli group. Unfortunately, even though the capsules for both groups looked the same, “true blinding was not possible,” and the patients knew which group they were in “because the pulverized broccoli sprouts could be easily distinguished from the methylcellulose [placebo] through their characteristic smell and taste.” So, we can’t discount the placebo effect. What’s more, the study participants weren’t properly randomized “because many of the patients refused to participate unless they were placed into the [active] treatment group.” That’s understandable, but it makes for a less rigorous result. A little broccoli can’t hurt, though, and it may help. It’s the lack of downsides of broccoli consumption that leads to “Advising Women Undergoing Treatment for Breast Cancer” to include the “liberal culinary use of cruciferous vegetables,” for example.
It’s the same for reducing saturated fat. The title of an editorial in a journal of the National Cancer Institute asked: “Is It Time to Give Breast Cancer Patients a Prescription for a Low-Fat Diet?” “Although counseling women to consume a healthy diet after breast cancer diagnosis is certainly warranted for general health, the existing data still fall a bit short of proving this will help reduce the risk of breast cancer recurrence and mortality.” But what do we have to lose? After all, it’s still certainly warranted for general health.
Michael Greger M.D. FACLM
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Treating Hashimoto’s Disease (Hypothyroidism) Naturally with Diet | NutritionFacts.org
What were the results of a randomized, double-blind, placebo-controlled trial of a daily half teaspoon of powdered black cumin in Hashimoto’s patients?
“Autoimmune thyroiditis, also known as Hashimoto’s thyroiditis, is an organ-specific autoimmune disorder,” where our body attacks our own thyroid gland, often leading to hypothyroidism due to destruction and scarring of the gland itself. We know there’s a genetic component, since identical twins are more likely to share the disease than fraternal twins. “However, even with identical twins, the concordance rate was only about 50%, emphasizing that important factors such as the environment play a role in disease pathogenesis.” Indeed, even if your identical twin, who has basically your exact same DNA, has the disease, there’s only like a flip of a coin’s chance you’ll get it. Genes load the gun, but the environment may pull the trigger.
More than 90 synthetic chemicals were noted to show disruption of hormonal balance or thyroid dysfunction.” However, only a few such ‘pollutants show evidence that they contribute to autoimmune thyroid disease.” These include polyaromatic hydrocarbons. Smokers get a lot of them from cigarettes, but in nonsmokers, exposure comes almost entirely from food, as you can see below and at 1:18 in my video Diet for Hypothyroidism: A Natural Treatment for Hashimoto’s Disease.
Polycyclic aromatic hydrocarbons are primarily formed when muscle meats, such as beef, pork, fish, or chicken, are cooked using high-temperature methods, such as grilling. PBBs, polybrominated biphenols, are a type of flame-retardant chemical no longer manufactured in the United States, but are still found in the aquatic food chain. PCBs, polychlorinated biphenols, are used in a number of industrial processes and end up in people’s bodies, again, largely through the consumption of fish, but also eggs and other meats, as seen here and at 1:41 in my video.
So, one might suspect those eating plant-based diets would have lower rates of hypothyroidism, and, indeed, despite their lower iodine intake, vegan diets tended to be protective. But they’ve never been put to the test in an interventional trial. A modification of the Paleolithic diet has been tried in Hashimoto’s patients, but it didn’t appear to improve thyroid function. What did, though, is Nigella Sativa. That name should sound familiar to anyone who’s read my book How Not to Diet or watched my live Evidence-Based Weight Loss presentation. Nigella Sativa is the scientific name for black cumin, which is just a simple spice that’s also used for a variety of medicinal purposes.
In one study, Hashimoto’s patients received a half teaspoon of powdered black cumin every day for eight weeks in a randomized, double-blind, placebo-controlled trial. Not only was there a significant reduction in body weight, which is why I profiled it in my book, but the black cumin also significantly reduced the thyroid-stimulating hormone, a sign that thyroid function was improving. It even lowered the level of autoimmune anti-thyroid antibodies, as well as increased blood levels of thyroid hormone T3 in these Hashimoto’s patients. In addition, there was a significant drop in Interleukin 23, a proinflammatory cell signal thought to help promote the autoimmune inflammation of the thyroid, which “further confirms the anti-inflammatory nature of the plant.” And what were the side effects? There was a 17 percent drop in “bad” LDL cholesterol, as shown below and at 3:19 in my video.
Given the fact that patients with Hashimoto’s may be at particularly high risk of developing heart disease, this is exactly the kind of side effects we’d want. “Considering these health-promoting effects of N. Sativa [black cumin], it can be considered as a therapeutic approach in the management of Hashimoto-related metabolic abnormalities.”
A similar trial failed to find a benefit, though. Same dose, same time frame, but no significant changes in thyroid function. In contrast with the previous study, though, the study participants were not all Hashimoto’s patients, but rather hypothyroid for any reason, and that may have diluted the results. And it’s possible that telling patients to take the black cumin doses with their thyroid hormone replacement therapy may have interfered with its absorption, which is an issue similar to other foods and drugs, and why patients are normally told to take it on an empty stomach. Since there are no downsides—it’s just a simple spice—I figure, why not give it a try? The worst that can happen is you’ll have tastier food.
Doctor’s Note:
I get a lot of questions about thyroid function, and I am glad to have been able to do this series. If you missed any of the other videos, see the related posts below.
For more on black cumin, see my book How Not to Diet and my presentation Evidence-Based Weight Loss.
Michael Greger M.D. FACLM
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