Semaglutide’s Surprisingly Unexamined Effects
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Semaglutide’s Surprisingly Big Research Gap
GLP-1 receptor agonists like Ozempic, Wegovy, and other semaglutide drugs. are fast becoming a health industry standard go-to tool in the weight loss toolbox. When it comes to recommending that patients lose weight, “Have you considered Ozempic?” is the common refrain.
Sometimes, this may be a mere case of kicking the can down the road with regard to some other treatment that it can be argued (sometimes even truthfully) would go better after some weight loss:
How weight bias in health care can harm patients with obesity: Research
…which we also covered in fewer words in the second-to-last item here:
But GLP-1 agonists work, right?
Yes, albeit there’s a litany of caveats, top of which are usually:
- there are often adverse gastrointestinal side effects
- if you stop taking them, weight regain generally ensues promptly
For more details on these and more, see:
…but now there’s another thing that’s come to light:
The dark side of semaglutide’s weight loss
In academia, “dark” is often used to describe “stuff we don’t have much (or in some cases, any) direct empirical evidence of, but for reasons of surrounding things, we know it’s there”.
Well-known examples include “dark matter” in physics and the Dark Ages in (European) history.
In the case of semaglutide and weight loss, a review by a team of researchers (Drs. Sandra Christenen, Katie Robinson, Sara Thomas, and Dominique Williams) has discovered how little research has been done into a certain aspect of GLP-1 agonist’s weight loss effects, namely…
Dietary changes!
There’s been a lot of popular talk about “people taking semaglutide eat less”, but it’s mostly anecdotal and/or presumed based on parts of the mechanism of action (increasing insulin production, reducing glucagon secretions, modulating dietary cravings).
Where studies have looked at dietary changes, it’s almost exclusively been a matter of looking at caloric intake (which has been found to be a 16–39% reduction), and observations-in-passing that patients reported reduction in cravings for fatty and sweet foods.
This reduction in caloric intake, by the way, is not significantly different to the reduction brought about by counselling alone (head-to-head studies have been done; these are also discussed in the research review).
However! It gets worse. Very few studies of good quality have been done, even fewer (two studies) actually had a registered dietitian nutritionist on the team, and only one of them used the “gold standard” of nutritional research, the 24-hour dietary recall test. Which, in case you’re curious, you can read about what that is here:
Dietary Assessment Methods: What Is A 24-Hour Recall?
Of the four studies that actually looked at the macros (unlike most studies), they found that on average, protein intake decreased by 17.1%. Which is a big deal!
It’s an especially big deal, because while protein’s obviously important for everyone, it’s especially important for anyone trying to lose weight, because muscle mass is a major factor in metabolic base rate—which in turn is much important for fat loss/maintenance than exercise, when it comes to how many calories we burn by simply existing.
A reasonable hypothesis, therefore, is that one of the numerous reasons people who quit GLP-1 agonists immediately put fat back on, is because they probably lost muscle mass in amongst their weight loss, meaning that their metabolic base rate will have decreased, meaning that they end up more disposed to put on fat than before.
And, that’s just a hypothesis and it’s a hypothesis based on very few studies, so it’s not something to necessarily take as any kind of definitive proof of anything, but it to say—as the researchers of this review do loudly say—more research needs to be done into this, because this has been a major gap in research so far!
Any other bad news?
While we’re talking research gaps, guess how many studies looked into micronutrient intake changes in people taking GLP-1 agonists?
If you guessed zero, you guessed correctly.
You can find the paper itself here:
What’s the main take-away here?
On a broad, scoping level: we need more research!
On a “what this means for individuals who want to lose weight” level: maybe we should be more wary of this still relatively new (less than 10 years old) “wonder drug”. And for most of those 10 years it’s only been for diabetics, with weight loss use really being in just the past few years (2021 onwards).
In other words: not necessarily any need to panic, but caution is probably not a bad idea, and natural weight loss methods remain very reasonable options for most people.
See also: How To Lose Weight (Healthily!)
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Clean Needles Save Lives. In Some States, They Might Not Be Legal.
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Kim Botteicher hardly thinks of herself as a criminal.
On the main floor of a former Catholic church in Bolivar, Pennsylvania, Botteicher runs a flower shop and cafe.
In the former church’s basement, she also operates a nonprofit organization focused on helping people caught up in the drug epidemic get back on their feet.
The nonprofit, FAVOR ~ Western PA, sits in a rural pocket of the Allegheny Mountains east of Pittsburgh. Her organization’s home county of Westmoreland has seen roughly 100 or more drug overdose deaths each year for the past several years, the majority involving fentanyl.
Thousands more residents in the region have been touched by the scourge of addiction, which is where Botteicher comes in.
She helps people find housing, jobs, and health care, and works with families by running support groups and explaining that substance use disorder is a disease, not a moral failing.
But she has also talked publicly about how she has made sterile syringes available to people who use drugs.
“When that person comes in the door,” she said, “if they are covered with abscesses because they have been using needles that are dirty, or they’ve been sharing needles — maybe they’ve got hep C — we see that as, ‘OK, this is our first step.’”
Studies have identified public health benefits associated with syringe exchange services. The Centers for Disease Control and Prevention says these programs reduce HIV and hepatitis C infections, and that new users of the programs are more likely to enter drug treatment and more likely to stop using drugs than nonparticipants.
This harm-reduction strategy is supported by leading health groups, such as the American Medical Association, the World Health Organization, and the International AIDS Society.
But providing clean syringes could put Botteicher in legal danger. Under Pennsylvania law, it’s a misdemeanor to distribute drug paraphernalia. The state’s definition includes hypodermic syringes, needles, and other objects used for injecting banned drugs. Pennsylvania is one of 12 states that do not implicitly or explicitly authorize syringe services programs through statute or regulation, according to a 2023 analysis. A few of those states, but not Pennsylvania, either don’t have a state drug paraphernalia law or don’t include syringes in it.
Those working on the front lines of the opioid epidemic, like Botteicher, say a reexamination of Pennsylvania’s law is long overdue.
There’s an urgency to the issue as well: Billions of dollars have begun flowing into Pennsylvania and other states from legal settlements with companies over their role in the opioid epidemic, and syringe services are among the eligible interventions that could be supported by that money.
The opioid settlements reached between drug companies and distributors and a coalition of state attorneys general included a list of recommendations for spending the money. Expanding syringe services is listed as one of the core strategies.
But in Pennsylvania, where 5,158 people died from a drug overdose in 2022, the state’s drug paraphernalia law stands in the way.
Concerns over Botteicher’s work with syringe services recently led Westmoreland County officials to cancel an allocation of $150,000 in opioid settlement funds they had previously approved for her organization. County Commissioner Douglas Chew defended the decision by saying the county “is very risk averse.”
Botteicher said her organization had planned to use the money to hire additional recovery specialists, not on syringes. Supporters of syringe services point to the cancellation of funding as evidence of the need to change state law, especially given the recommendations of settlement documents.
“It’s just a huge inconsistency,” said Zoe Soslow, who leads overdose prevention work in Pennsylvania for the public health organization Vital Strategies. “It’s causing a lot of confusion.”
Though sterile syringes can be purchased from pharmacies without a prescription, handing out free ones to make drug use safer is generally considered illegal — or at least in a legal gray area — in most of the state. In Pennsylvania’s two largest cities, Philadelphia and Pittsburgh, officials have used local health powers to provide legal protection to people who operate syringe services programs.
Even so, in Philadelphia, Mayor Cherelle Parker, who took office in January, has made it clear she opposes using opioid settlement money, or any city funds, to pay for the distribution of clean needles, The Philadelphia Inquirer has reported. Parker’s position signals a major shift in that city’s approach to the opioid epidemic.
On the other side of the state, opioid settlement funds have had a big effect for Prevention Point Pittsburgh, a harm reduction organization. Allegheny County reported spending or committing $325,000 in settlement money as of the end of last year to support the organization’s work with sterile syringes and other supplies for safer drug use.
“It was absolutely incredible to not have to fundraise every single dollar for the supplies that go out,” said Prevention Point’s executive director, Aaron Arnold. “It takes a lot of energy. It pulls away from actual delivery of services when you’re constantly having to find out, ‘Do we have enough money to even purchase the supplies that we want to distribute?’”
In parts of Pennsylvania that lack these legal protections, people sometimes operate underground syringe programs.
The Pennsylvania law banning drug paraphernalia was never intended to apply to syringe services, according to Scott Burris, director of the Center for Public Health Law Research at Temple University. But there have not been court cases in Pennsylvania to clarify the issue, and the failure of the legislature to act creates a chilling effect, he said.
Carla Sofronski, executive director of the Pennsylvania Harm Reduction Network, said she was not aware of anyone having faced criminal charges for operating syringe services in the state, but she noted the threat hangs over people who do and that they are taking a “great risk.”
In 2016, the CDC flagged three Pennsylvania counties — Cambria, Crawford, and Luzerne — among 220 counties nationwide in an assessment of communities potentially vulnerable to the rapid spread of HIV and to new or continuing high rates of hepatitis C infections among people who inject drugs.
Kate Favata, a resident of Luzerne County, said she started using heroin in her late teens and wouldn’t be alive today if it weren’t for the support and community she found at a syringe services program in Philadelphia.
“It kind of just made me feel like I was in a safe space. And I don’t really know if there was like a come-to-God moment or come-to-Jesus moment,” she said. “I just wanted better.”
Favata is now in long-term recovery and works for a medication-assisted treatment program.
At clinics in Cambria and Somerset Counties, Highlands Health provides free or low-cost medical care. Despite the legal risk, the organization has operated a syringe program for several years, while also testing patients for infectious diseases, distributing overdose reversal medication, and offering recovery options.
Rosalie Danchanko, Highlands Health’s executive director, said she hopes opioid settlement money can eventually support her organization.
“Why shouldn’t that wealth be spread around for all organizations that are working with people affected by the opioid problem?” she asked.
In February, legislation to legalize syringe services in Pennsylvania was approved by a committee and has moved forward. The administration of Gov. Josh Shapiro, a Democrat, supports the legislation. But it faces an uncertain future in the full legislature, in which Democrats have a narrow majority in the House and Republicans control the Senate.
One of the bill’s lead sponsors, state Rep. Jim Struzzi, hasn’t always supported syringe services. But the Republican from western Pennsylvania said that since his brother died from a drug overdose in 2014, he has come to better understand the nature of addiction.
In the committee vote, nearly all of Struzzi’s Republican colleagues opposed the bill. State Rep. Paul Schemel said authorizing the “very instrumentality of abuse” crossed a line for him and “would be enabling an evil.”
After the vote, Struzzi said he wanted to build more bipartisan support. He noted that some of his own skepticism about the programs eased only after he visited Prevention Point Pittsburgh and saw how workers do more than just hand out syringes. These types of programs connect people to resources — overdose reversal medication, wound care, substance use treatment — that can save lives and lead to recovery.
“A lot of these people are … desperate. They’re alone. They’re afraid. And these programs bring them into someone who cares,” Struzzi said. “And that, to me, is a step in the right direction.”
At her nonprofit in western Pennsylvania, Botteicher is hoping lawmakers take action.
“If it’s something that’s going to help someone, then why is it illegal?” she said. “It just doesn’t make any sense to me.”
This story was co-reported by WESA Public Radio and Spotlight PA, an independent, nonpartisan, and nonprofit newsroom producing investigative and public-service journalism that holds power to account and drives positive change in Pennsylvania.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
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The Circadian Code – by Dr. Satchin Panda
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There’s a lot more to circadian rhythm than “sleep during these hours”. And there’s a lot more to bear in mind than “don’t have blue/white light at night”.
In fact, Dr. Satchin Panda explains, there’s a whole daily symphony of movements in our body as different biochemical processes wax and wane according to what time of day it is.
There are several important things he wants us to know about this:
- Our body needs to know what time it is, for those processes to work correctly
- Because of these daily peaks and troughs of various physiological functions, we get “correct” times for things we do every day. Not just sleeping/waking, but also:
- The best time to eat
- The best time to exercise
- The best time to do mental work
- The best times to take different kinds of supplements/medications
Dr. Panda also looks at what things empower, or disempower, our body to keep track of what time it is.
Bottom line: if you’d like to optimize your days and your health, this book has a lot of very valuable practicable tips.
Click here to check out The Circadian Code, and make the most of yours!
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Vodka vs Beer – Which is Healthier?
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Our Verdict
When comparing vodka to beer, we picked the vodka.
Why?
As you might have guessed, neither are exactly healthy. But one of them is relatively, and we stress relatively, less bad than the other.
In the category of nutrients, vodka is devoid of nutrients, and beer has small amounts of some vitamins and minerals—but the amounts are so small, that you would need to drink yourself to death before benefiting from them meaningfully. And while beer gets touted as “liquid bread”, it really isn’t. A thousand years ago it will have been a lot less alcoholic and more carby, but even then, it wasn’t a health product aside from that it provided a way of making potentially contaminated water safer to drink.
In the category of carbohydrates, vodka nominally has none, due to the distillation process, and beer has some. Glycemic index websites often advise that the GI of beers, wines, and spirits can’t be measured as their carb content is not sufficient to get a meaningful sample, but diabetes research tells a more useful story:
Any alcoholic drink will generally cause a brief drop in blood sugars, followed by a spike. This happens because the liver prioritises metabolizing alcohol over producing glycogen, so it hits pause on the sugar metabolism and then has a backlog to catch up on. In the case of alcoholic drinks that have alcohol and carbs, this will be more pronounced—so this means that the functional glycemic load of beer is higher.
That’s a point in favor of vodka.
Additionally, in terms of the alcohol content, correctly-distilled vodka’s alcohol is pure ethanol, while beer will contain an amount of methanol that will vary per beer, but an illustrative nominal figure could be about 16mg/L. Methanol is more harmful than ethanol.
So that’s another point in favor of vodka.
Once again, neither drink is healthy; both are distinctly unhealthy. But unit for unit, beer is the least healthy of the two, making vodka the lesser of two evils.
Want to learn more?
You might like to read:
- Can We Drink To Good Health? (answer: we cannot, but this was about alcohol’s proposed heart-healthy benefits)
- Guinness Is Good For You* (it isn’t, but this was the long-time slogan and marketing campaign that fooled many)
- How To Reduce Or Quit Alcohol
- How To Unfatty A Fatty Liver
Take care!
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Healthy Habits For Your Heart – by Monique Tello
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Did you guess we’d review this one today? Well, you’ve already had a taste of what Dr. Tello has to offer, but if you want to take your heart health seriously, this incredibly accessible guide is excellent.
Because Dr. Tello doesn’t assume prior knowledge, the first part of the book (the first three chapters) are given over to “heart and habit basics”—heart science, the effect your lifestyle can have on such, and how to change your habits.
The second part of the book is rather larger, and addresses changing foundational habits, nutrition habits, weight loss/maintenance, healthy activity habits, and specifically addressing heart-harmful habits (especially drinking, smoking, and the like).
She then follows up with a section of recipes, references, and other useful informational appendices.
The writing style throughout is super simple and clear, even when giving detailed clinical information. This isn’t a dusty old doctor who loves the sound of their own jargon, this is good heart health rendered as easy and accessible as possible to all.
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Strawberries vs Blackberries – Which is Healthier?
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Our Verdict
When comparing strawberries to blackberries, we picked the blackberries.
Why?
Shocking nobody, both are very healthy options. However, blackberries do come out on top:
In terms of macros, the main thing that sets them apart is that blackberries have more than 2x the fiber. Other differences in macros are also in blackberries’ favor, but only very marginally, so we’ll not distract with those here. The fiber difference is distinctly significant, though.
In the category of vitamins, blackberries lead with more of vitamins A, B2, B3, B5, B9, E, and K, as well as more choline. Meanwhile, strawberries boast more of vitamins B1, B6, and C. So, a 8:2 advantage for blackberries (and some of the margins are very large, such as 9x more choline, 4x more vitamin E, and nearly 18x more vitamin A).
When it comes to minerals, things are not less clear: blackberries have considerably more calcium, copper, iron, magnesium, manganese, and zinc. The two fruits are equal in other minerals that they both contain, and strawberries don’t contain any mineral in greater amounts than blackberries do.
A discussion of these berries’ health benefits would be incomplete without at least mentioning polyphenols, but both of them are equally good sources of such, so there’s no distinction to set one above the other in this category.
As ever, enjoy both, though! Diversity is good.
Want to learn more?
You might like to read:
- Strawberries vs Cherries – Which is Healthier?
- Blackberries vs Blueberries – Which is Healthier?
- Strawberries vs Raspberries – Which is Healthier?
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Blood-Brain Barrier Breach Blamed For Brain-Fog
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Move Over, Leaky Gut. Now It’s A Leaky Brain.
…which is not a headline that promises good news, and indeed, the only good news about this currently is “now we know another thing that’s happening, and thus can work towards a treatment for it”.
Back in February (most popular media outlets did not rush to publish this, as it rather goes against the narrative of “remember when COVID was a thing?” as though the numbers haven’t risen since the state of emergency was declared over), a team of Irish researchers made a discovery:
❝For the first time, we have been able to show that leaky blood vessels in the human brain, in tandem with a hyperactive immune system may be the key drivers of brain fog associated with long covid❞
~ Dr. Matthew Campbell (one of the researchers)
Let’s break that down a little, borrowing some context from the paper itself:
- the leaky blood vessels are breaching the blood-brain-barrier
- that’s a big deal, because that barrier is our only filter between our brain and Things That Definitely Should Not Go In The Brain™
- a hyperactive immune system can also be described as chronic inflammation
- in this case, that includes chronic neuroinflammation which, yes, is also a major driver of dementia
You may be wondering what COVID has to do with this, and well:
- these blood-brain-barrier breaches were very significantly associated (in lay terms: correlated, but correlated is only really used as an absolute in write-ups) with either acute COVID infection, or Long Covid.
- checking this in vitro, exposure of brain endothelial cells to serum from patients with Long Covid induced the same expression of inflammatory markers.
How important is this?
As another researcher (not to mention: professor of neurology and head of the school of medicine at Trinity) put it:
❝The findings will now likely change the landscape of how we understand and treat post-viral neurological conditions.
It also confirms that the neurological symptoms of long covid are measurable with real and demonstrable metabolic and vascular changes in the brain.❞
~ Dr. Colin Doherty (see mini-bio above)
You can read a pop-science article about this here:
Irish researchers discover underlying cause of “brain fog” linked with long covid
…and you can read the paper in full here:
Want to stay safe?
Beyond the obvious “get protected when offered boosters/updates” (see also: The Truth About Vaccines), other good practices include the same things most people were doing when the pandemic was big news, especially avoiding enclosed densely-populated places, washing hands frequently, and looking after your immune system. For that latter, see also:
Beyond Supplements: The Real Immune-Boosters!
Take care!
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- the leaky blood vessels are breaching the blood-brain-barrier