Metformin For Weight-Loss & More
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Metformin Without Diabetes?
Metformin is a diabetes drug; it works by:
- decreasing glucose absorption from the gut
- decreasing glucose production in the liver
- increasing glucose sensitivity
It doesn’t change how much insulin is secreted, and is unlikely to cause hypoglycemia, making it relatively safe as diabetes drugs go.
It’s a biguanide drug, and/but so far as science knows (so far), its mechanism of action is unique (i.e. no other drug works the same way that metformin does).
Today we’ll examine its off-label uses and see what the science says!
A note on terms: “off-label” = when a drug is prescribed to treat something other than the main purpose(s) for which the drug was approved.
Other examples include modafinil against depression, and beta-blockers against anxiety.
Why take it if not diabetic?
There are many reasons people take it, including just general health and life extension:
However, its use was originally expanded (still “off-label”, but widely prescribed) past “just for diabetes” when it showed efficacy in treating pre-diabetes. Here for example is a longitudinal study that found metformin use performed similarly to lifestyle interventions (e.g. diet, exercise, etc). In their words:
❝ Lifestyle intervention or metformin significantly reduced diabetes development over 15 years. There were no overall differences in the aggregate microvascular outcome between treatment groups❞
But, it seems it does more, as this more recent review found:
❝Long-term weight loss was also seen in both [metformin and intensive lifestyle intervention] groups, with better maintenance under metformin.
Subgroup analyses from the DPP/DPPOS have shed important light on the actions of metformin, including a greater effect in women with prior gestational diabetes, and a reduction in coronary artery calcium in men that might suggest a cardioprotective effect.
Long-term diabetes prevention with metformin is feasible and is supported in influential guidelines for selected groups of subjects.❞
Source: Metformin for diabetes prevention: update of the evidence base
We were wondering about that cardioprotective effect, so…
Cardioprotective effect
In short, another review (published a few months after the above one) confirmed the previous findings, and also added:
❝Patients with BMI > 35 showed an association between metformin use and lower incidence of CVD, including African Americans older than age 65. The data suggest that morbidly obese patients with prediabetes may benefit from the use of metformin as recommended by the ADA.❞
We wondered about the weight loss implications of this, and…
For weight loss
The short version is, it works:
- Effectiveness of metformin on weight loss in non-diabetic individuals with obesity
- Metformin for weight reduction in non-diabetic patients: a systematic review and meta-analysis
- Metformin induces weight loss associated with gut microbiota alteration in non-diabetic obese women
…and many many more where those came from. As a point of interest, it has also been compared and contrasted to GLP-1 agonists.
Compared/contrasted with GLP-1 agonists
It’s not quite as effective for weight loss, and/but it’s a lot cheaper, is tablets rather than injections, has fewer side effects (for most people), and doesn’t result in dramatic yoyo-ing if there’s an interruption to taking it:
Or if you prefer a reader-friendly pop-science version:
Ozempic vs Metformin: Comparing The Two Diabetes Medications
Is it safe?
For most people yes, but there are a stack of contraindications, so it’s best to speak with your doctor. However, particular things to be aware of include:
- Usually contraindicated if you have kidney problems of any kind
- Usually contraindicated if you have liver problems of any kind
- May be contraindicated if you have issues with B12 levels
See also: Metformin: Is it a drug for all reasons and diseases?
Where can I get it?
As it’s a prescription-controlled drug, we can’t give you a handy Amazon link for this one.
However, many physicians are willing to prescribe it for off-label use (i.e., for reasons other than diabetes), so speak with yours (telehealth options may also be available).
If you do plan to speak with your doctor and you’re not sure they’ll be agreeable, you might want to get this paper and print it to take it with you:
Off-label indications of Metformin – Review of Literature
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What Flexible Dieting Really Means
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When Flexibility Is The Dish Of The Day
This is Alan Aragon. Notwithstanding not being a “Dr. Alan Aragon”, he’s a research scientist with dozens of peer-reviewed nutrition science papers to his name, as well as being a personal trainer and fitness educator. Most importantly, he’s an ardent champion of making people’s pursuit of health and fitness more evidence-based.
We’ll be sharing some insights from a book of his that we haven’t reviewed yet, but we will link it at the bottom of today’s article in any case.
What does he want us to know?
First, get out of the 80s and into the 90s
In the world of popular dieting, the 80s were all about calorie-counting and low-fat diets. They did not particularly help.
In the 90s, it was discovered that not only was low-fat not the way to go, but also, regardless of the diet in question, rigid dieting leads to “disinhibition”, that is to say, there comes a point (usually not far into a diet) whereby one breaks the diet, at which point, the floodgates open and the dieter binges unhealthily.
Aragon would like to bring our attention to a number of studies that found this in various ways over the course of the 90s measuring various different metrics including rigid vs flexible dieting’s impacts on BMI, weight gain, weight loss, lean muscle mass changes, binge-eating, anxiety, depression, and so forth), but we only have so much room here, so here’s a 1999 study that’s pretty much the culmination of those:
Flexible vs. Rigid Dieting Strategies: Relationship with Adverse Behavioral Outcomes
So in short: trying to be very puritan about any aspect of dieting will not only not work, it will backfire.
Next, get out of the 90s into the 00s
…which is not only fun if you read “00s” out loud as “naughties”, but also actually appropriate in this case, because it is indeed important to be comfortable being a little bit naughty:
In 2000, Dr. Marika Tiggemann found that dichotomous perceptions of food (e.g. good/bad, clean/dirty, etc) were implicated as a dysfunctional cognitive style, and predicted not only eating disorders and mood disorders, but also adverse physical health outcomes:
Dieting and Cognitive Style: The Role of Current and Past Dieting Behaviour and Cognitions
This was rendered clearer, in terms of physical health outcomes, by Dr. Susan Byrne & Dr. Emma Dove, in 2009:
❝Weight loss was negatively associated with pre-treatment depression and frequency of treatment attendance, but not with dichotomous thinking. Females who regard their weight as unacceptably high and who think dichotomously may experience high levels of depression irrespective of their actual weight, while depression may be proportionate to the degree of obesity among those who do not think dichotomously❞
Aragon’s advice based on all this: while yes, some foods are better than others, it’s more useful to see foods as being part of a spectrum, rather than being absolutist or “black and white” about it.
Next: hit those perfect 10s… Imperfectly
The next decade expanded on this research, as science is wont to do, and for this one, Aragon shines a spotlight on Dr. Alice Berg’s 2018 study with obese women averaging 69 years of age, in which…
In other words (and in fact, to borrow Dr. Berg’s words from that paper),
❝encouraging a flexible approach to eating behavior and discouraging rigid adherence to a diet may lead to better intentional weight loss for overweight and obese older women❞
You may be wondering: what did this add to the studies from the 90s?
And the key here is: rather than being observational, this was interventional. In other words, rather than simply observing what happened to people who thought one way or another, this study took people who had a rigid, dichotomous approach to food, and gave them a 6-month behavioral intervention (in other words, support encouraging them to be more flexible and open in their approach to food), and found that this indeed improved matters for them.
Which means, it’s not a matter of fate or predisposition, as it could have been back in the 90s, per “some people are just like that; who’s to say which factor causes which”. Instead, now we know that this is an approach that can be adopted, and it can be expected to work.
Beyond weight loss
Now, so far we’ve talked mostly about weight loss, and only touched on other health outcomes. This is because:
- weight loss a very common goal for many
- it’s easy to measure so there’s a lot of science for it
Incidentally, if it’s a goal of yours, here’s what 10almonds had to say about that, along with two follow-up articles for other related goals:
Spoiler: we agree with Aragon, and recommend a relaxed and flexible approach to all three of these things
Aragon’s evidence-based approach to nutrition has found that this holds true for other aspects of healthy eating, too. For example…
To count or not to count?
It’s hard to do evidence-based anything without counting, and so Aragon talks a lot about this. Indeed, he does a lot of counting in scientific papers of his own, such as:
and
The effect of protein timing on muscle strength and hypertrophy: a meta-analysis
…as well as non-protein-related but diet-related topics such as:
But! For the at-home health enthusiast, Aragon recommends that the answer to the question “to count or not to count?” is “both”:
- Start off by indeed counting and tracking everything that is important to you (per whatever your current personal health intervention is, so it might be about calories, or grams of protein, or grams of carbs, or a certain fat balance, or something else entirely)
- Switch to a more relaxed counting approach once you get used to the above. By now you probably know the macros for a lot of your common meals, snacks, etc, and can tally them in your head without worrying about weighing portions and knowing the exact figures.
- Alternatively, count moderately standardized portions of relevant foods, such as “three servings of beans or legumes per day” or “no more than one portion of refined carbohydrates per day”
- Eventually, let habit take the wheel. Assuming you have established good dietary habits, this will now do you just fine.
This latter is the point whereby the advice (that Aragon also champions) of “allow yourself an unhealthy indulgence of 10–20% of your daily food”, as a budget of “discretionary calories”, eventually becomes redundant—because chances are, you’re no longer craving that donut, and at a certain point, eating foods far outside the range of healthiness you usually eat is not even something that you would feel inclined to do if offered.
But until that kicks in, allow yourself that budget of whatever unhealthy thing you enjoy, and (this next part is important…) do enjoy it.
Because it is no good whatsoever eating that cream-filled chocolate croissant and then feeling guilty about it; that’s the dichotomous thinking we had back in the 80s. Decide in advance you’re going to eat and enjoy it, then eat and enjoy it, then look back on it with a sense of “that was enjoyable” and move on.
The flipside of this is that the importance of allowing oneself a “little treat” is that doing so actively helps ensure that the “little treat” remains “little”. Without giving oneself permission, then suddenly, “well, since I broke my diet, I might as well throw the whole thing out the window and try again on Monday”.
On enjoying food fully, by the way:
Mindful Eating: How To Get More Nutrition Out Of The Same Food
Want to know more from Alan Aragon?
Today we’ve been working heavily from this book of his; we haven’t reviewed it yet, but we do recommend checking it out:
Enjoy!
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No Time to Panic – by Matt Gutman
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Matt Gutman is not a doctor or a psychologist. He’s a journalist, accustomed to asking questions and then asking more probing questions, unrelenting until he gets the answers he’s looking for.
This book is the result of what happened when he needed to overcome his own anxiety and panic attacks, and went on an incisive investigative journey.
The style is as clear and accessible as you’d expect of a journalist, and presents a very human exploration, nonetheless organized in a way that will be useful to the reader.
It’s said that “experience is a great teacher, but she sends hefty bills”. In this case as in many, it’s good to learn from someone else’s experience!
By the end of the book, you’ll have a good grounding in most approaches to dealing with anxiety and panic attacks, and an idea of efficacy/applicability, and what to expect.
Bottom line: without claiming any magic bullet, this book presents six key strategies that Gutman found to work, along with his experiences of what didn’t. Valuable reading if you want to curb your own anxiety, or want to be able to help/support someone else with theirs.
Click here to check out No Time To Panic, and find the peace you deserve!
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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
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Grapefruit vs Orange – Which is Healthier?
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Our Verdict
When comparing grapefruit to orange, we picked the orange.
Why?
It’s easy, when guessing which is the healthier out of two things, to guess that the more expensive or perhaps less universally available one is the healthier. But it’s not always so, and today is one of those cases!
In terms of macros, they are very similar fruits, with almost identical levels of carbohydrates, proteins, and fats, as well as water. Looking more carefully, we find that grapefruit’s sugars contain a slightly high proportion of fructose; not enough to make it unhealthy by any means (indeed, no whole unprocessed fruit is unhealthy unless it’s literally poisonous), but it is a thing to note if we’re micro-analysing the macronutrients. Also, oranges have slightly more fiber, which is always a plus.
When it comes to vitamins, oranges stand out with more of vitamins B1, B2, B3, B6, B9, C, and E, while grapefruit boasts more vitamin A (hence its color). Still, we’re calling this category another win for oranges.
In the category of minerals, oranges again sweep with more calcium, copper, iron, magnesium, manganese, potassium, and selenium, while grapefruit has just a little more phosphorus. So, another easy win for oranges.
One final consideration that’s not shown in the nutritional values, is that grapefruit contains furanocoumarin, which can inhibit cytochrome P-450 3A4 isoenzyme and P-glycoptrotein transporters in the intestine and liver—slowing down their drug metabolism capabilities, thus effectively increasing the bioavailability of many drugs manifold. It can also be found in lower quantities in Seville (sour) oranges, and it’s not present (or at least, if it is, it’s in truly tiny quantities) in most oranges.
This may sound superficially like a good thing (improving bioavailability of things we want), but in practice it means that in the case of many drugs, if you take them with (or near in time to) grapefruit or grapefruit juice, then congratulations, you just took an overdose. This happens with a lot of meds for blood pressure, cholesterol (including statins), calcium channel-blockers, anti-depressants, benzo-family drugs, beta-blockers, and more. Oh, and Viagra, too. Which latter might sound funny, but remember, Viagra’s mechanism of action is blood pressure modulation, and that is not something you want to mess around with unduly. So, do check with your pharmacist to know if you’re on any meds that would be affected by grapefruit or grapefruit juice!
All in all, today’s sections add up to an overwhelming win for oranges!
Want to learn more?
You might like to read:
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Is “Extra Virgin” Worth It?
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It’s Q&A Day at 10almonds!
Have a question or a request? We love to hear from you!
In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!
As ever: if the question/request can be answered briefly, we’ll do it here in our Q&A Thursday edition. If not, we’ll make a main feature of it shortly afterwards!
So, no question/request too big or small
❝I was wondering, is the health difference important between extra virgin olive oil and regular?❞
Assuming that by “regular” you mean “virgin and still sold as a food product”, then there are health differences, but they’re not huge. Or at least: not nearly so big as the differences between those and other oils.
Virgin olive oil (sometimes simply sold as “olive oil”, with no claims of virginity) has been extracted by the same means as extra virgin olive oil, that is to say: purely mechanical.
The difference is that extra virgin olive oil comes from the first pressing*, so the free fatty acid content is slightly lower (later checked and validated and having to score under a 0.8% limit for “extra virgin” instead of 2% limit for a mere “virgin”).
*Fun fact: in Arabic, extra virgin is called “البكر الممتاز“, literally “the amazing first-born”, because of this feature!
It’s also slightly higher in mono-unsaturated fatty acids, which is a commensurately slight health improvement.
It’s very slightly lower in saturated fats, which is an especially slight health improvement, as the saturated fats in olive oil are amongst the healthiest saturated fats one can consume.
On which fats are which:
The truth about fats: the good, the bad, and the in-between
And our own previous discussion of saturated fats in particular:
Can Saturated Fats Be Healthy?
Probably the strongest extra health-benefit of extra virgin is that while that first pressing squeezes out oil with the lowest free fatty acid content, it squeezes out oil with the highest polyphenol content, along with other phytonutrients:
If you enjoy olive oil, then springing for extra virgin is worth it if that’s not financially onerous, both for health reasons and taste.
However, if mere “virgin” is what’s available, it’s no big deal to have that instead; it still has a very similar nutritional profile, and most of the same benefits.
Don’t settle for less than “virgin”, though.
While some virgin olive oils aren’t marked as such, if it says “refined” or “blended”, then skip it. These will have been extracted by chemical means and/or blended with completely different oils (e.g. canola, which has a very different nutritional profile), and sometimes with a dash of virgin or extra virgin, for the taste and/or so that they can claim in big writing on the label something like:
a blend of
EXTRA VIRGIN OLIVE OIL
and other oils…despite having only a tiny amount of extra virgin olive oil in it.
Different places have different regulations about what labels can claim.
The main countries that produce olives (and the EU, which contains and/or directly trades with those) have this set of rules:
International Olive Council: Designations and definitions of Olive Oils
…which must be abided by or marketers face heavy fines and sanctions.
In the US, the USDA has its own set of rules based on the above:
USDA | Olive Oil and Olive-Pomace Oil Grades and Standards
…which are voluntary (not protected by law), and marketers can pay to have their goods certified if they want.
So if you’re in the US, look for the USDA certification or it really could be:
- What the USDA calls “US virgin olive oil not fit for human consumption”, which in the IOC is called “lamp oil”*
- crude pomace-oil (oil made from the last bit of olive paste and then chemically treated)
- canola oil with a dash of olive oil
- anything yellow and oily, really
*This technically is virgin olive oil insofar as it was mechanically extracted, but with defects that prevent it from being sold as such, such as having a free fatty acid content above the cut-off, or just a bad taste/smell, or some sort of contamination.
See also: Potential Health Benefits of Olive Oil and Plant Polyphenols
(the above paper has a handy infographic if you scroll down just a little)
Where can I get some?
Your local supermarket, probably, but if you’d like to get some online, here’s an example product on Amazon for your convenience
Enjoy!
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Can kimchi really help you lose weight? Hold your pickle. The evidence isn’t looking great
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Fermented foods have become popular in recent years, partly due to their perceived health benefits.
For instance, there is some evidence eating or drinking fermented foods can improve blood glucose control in people with diabetes. They can lower blood lipid (fats) levels and blood pressure in people with diabetes or obesity. Fermented foods can also improve diarrhoea symptoms.
But can they help you lose weight, as a recent study suggests? Let’s look at the evidence.
Remind me, what are fermented foods?
Fermented foods are ones prepared when microbes (bacteria and/or yeast) ferment (or digest) food components to form new foods. Examples include yoghurt, cheese, kefir, kombucha, wine, beer, sauerkraut and kimchi.
As a result of fermentation, the food becomes acidic, extending its shelf life (food-spoilage microbes are less likely to grow under these conditions). This makes fermentation one of the earliest forms of food processing.
Fermentation also leads to new nutrients being made. Beneficial microbes (probiotics) digest nutrients and components in the food to produce new bioactive components (postbiotics). These postbiotics are thought to contribute to the health benefits of the fermented foods, alongside the health benefits of the bacteria themselves.
What does the evidence say?
A study published last week has provided some preliminary evidence eating kimchi – the popular Korean fermented food – is associated with a lower risk of obesity in some instances. But there were mixed results.
The South Korean study involved 115,726 men and women aged 40-69 who reported how much kimchi they’d eaten over the previous year. The study was funded by the World Institute of Kimchi, which specialises in researching the country’s national dish.
Eating one to three servings of any type of kimchi a day was associated with a lower risk of obesity in men.
Men who ate more than three serves a day of cabbage kimchi (baechu) were less likely to have obesity and abdominal obesity (excess fat deposits around their middle). And women who ate two to three serves a day of baechu were less likely to have obesity and abdominal obesity.
Eating more radish kimchi (kkakdugi) was associated with less abdominal obesity in both men and women.
However, people who ate five or more serves of any type of kimchi weighed more, had a larger waist sizes and were more likely to be obese.
The study had limitations. The authors acknowledged the questionnaire they used may make it difficult to say exactly how much kimchi people actually ate.
The study also relied on people to report past eating habits. This may make it hard for them to accurately recall what they ate.
This study design can also only tell us if something is linked (kimchi and obesity), not if one thing causes another (if kimchi causes weight loss). So it is important to look at experimental studies where researchers make changes to people’s diets then look at the results.
How about evidence from experimental trials?
There have been several experimental studies looking at how much weight people lose after eating various types of fermented foods. Other studies looked at markers or measures of appetite, but not weight loss.
One study showed the stomach of men who drank 1.4 litres of fermented milk during a meal took longer to empty (compared to those who drank the same quantity of whole milk). This is related to feeling fuller for longer, potentially having less appetite for more food.
Another study showed drinking 200 millilitres of kefir (a small glass) reduced participants’ appetite after the meal, but only when the meal contained quickly-digested foods likely to make blood glucose levels rise rapidly. This study did not measure changes in weight.
Kefir, a fermented milk drink, reduced people’s appetite.
Ildi Papp/ShutterstockAnother study looked at Indonesian young women with obesity. Eating tempeh (a fermented soybean product) led to changes in an appetite hormone. But this did not impact their appetite or whether they felt full. Weight was not measured in this study.
A study in South Korea asked people to eat about 70g a day of chungkookjang (fermented soybean). There were improvements in some measures of obesity, including percentage body fat, lean body mass, waist-to-hip ratio and waist circumference in women. However there were no changes in weight for men or women.
A systematic review of all studies that looked at the impact of fermented foods on satiety (feeling full) showed no effect.
What should I do?
The evidence so far is very weak to support or recommend fermented foods for weight loss. These experimental studies have been short in length, and many did not report weight changes.
To date, most of the studies have used different fermented foods, so it is difficult to generalise across them all.
Nevertheless, fermented foods are still useful as part of a healthy, varied and balanced diet, particularly if you enjoy them. They are rich in healthy bacteria, and nutrients.
Are there downsides?
Some fermented foods, such as kimchi and sauerkraut, have added salt. The latest kimchi study said the average amount of kimchi South Koreans eat provides about 490mg of salt a day. For an Australian, this would represent about 50% of the suggested dietary target for optimal health.
Eating too much salt increases your risk of high blood pressure, heart disease and stroke.
Evangeline Mantzioris, Program Director of Nutrition and Food Sciences, Accredited Practising Dietitian, University of South Australia
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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