TOPLEY’S TOP 10 May 13, 2025

Daily Top Ten No Comments

1. The Countries “Projected” to Take Over Economic Leadership vs. America are Bleeding High Net Worth Citizens—China, UK, and India

First Trust Economic Blog

2. Investors Buying Defensive Sectors Pre-China Trade Announcement

Credit: BofA’s private clients have been exiting leveraged finance assets.

The Daily Shot

3. Investors Get Defensive but QQQ Closes Above 200-Day

Subu Trade

4. Coinbase Joins S&P 500—Sits $150 Off 2024 Highs

StockCharts

5. Charles Schwab $10 Trillion in Assets Under Management—Breaks Out to New Highs

StockCharts

6. April Large Budget Surplus

Presenting Exhibit A: in April, the US Treasury generated a $258.4 billion surplus after last month’s $160.5 billion deficit; this the second biggest surplus on record, with just the $308 billion bumper surplus in 2021 bigger.

ZeroHedge

7. Trump in Saudi Arabia Asking for Investment in U.S. but MBS Betting Trillions on Home Mega Projects

Bloomberg

8. Latin American Exports 42% to U.S.

Semafor

9. How Do Universities Make Money?

Voronoi

10. Stop Chasing Comfort, Start Building the Future You

Stop Chasing Comfort, Start Building the Future YouThe future you is an unfinished prototype.

KEY POINTS

  • Growth comes from embracing discomfort, not from seeking comfort or immediate results.
  • Identity evolution requires releasing outdated roles and accepting productive discomfort.
  • Mental toughness and resilience are built by pushing through perceived limits, not avoiding them.
  • Psychological safety and feedback are essential for personal development and successful transitions.

Via Psychology Today: In a world obsessed with instant results, busyness is often mistaken for progress. Meetings, emails, and endless tasks can create the illusion of momentum, but are we moving forward? True growth doesn’t come from checking boxes; it comes from leaning into the uncomfortable, uncertain work of becoming who we’re meant to be.

Psychologists like Walter Mischel and Carol Dweck have shown that while we’re wired for immediate gratification, lasting development requires embracing productive discomfort. Discomfort, in the right context, isn’t a warning sign; it’s proof that growth is happening.

The best leaders, teams, and organizations don’t avoid discomfort, they use it. It’s their edge for innovation, resilience, and transformation.—Brene Brown, University of Houston

The future you is an unfinished prototype

Through repeated endurance challenges, I discovered the true power of the 40 Percent Rule: the real limit isn’t physical, it’s mental. Discomfort wasn’t a sign to stop; it was my mind clinging to the familiar. Resilience isn’t just about pushing through, it’s about realizing how much more you’re capable of.

These experiences revealed something deeper: discomfort isn’t the enemy, it’s the entry point. Life’s transitions, whether chosen or forced, are often uncomfortable. But that discomfort? It’s not just to be survived, it’s a catalyst for growth.

Five ways to embrace it.

1. Lean Into Stretch Experiences

Growth rarely happens in comfort. Transitions often feel heavy because we carry the weight of outdated expectations and identity scripts. Our narrative identity is the evolving story we tell ourselves about who we are. To move forward with intention, we must first release what no longer serves us. Rituals of release, like writing a letter to your former self and burning it or leaving behind a symbolic object on a walk, can create psychological closure, a process linked to emotional integration and renewal.

Next, seek out stretch experiences: take a solo trip, learn a new skill, or pursue a goal that intimidates you. These challenges activate the growth mindset, the belief that abilities evolve through effort. Stretching yourself builds confidence, neural adaptability, and a deeper capacity for uncertainty.

The goal isn’t to erase the past. It’s to loosen your grip on who you were, so you can grow into who you’re becoming.

2. Invite Honest Feedback and Self-Reflection

Life transitions often trigger identity dissonance: the uncomfortable gap between your past self and your emerging one. Clinging to outdated roles, like the overachiever, the people-pleaser, or the expert, can lead to identity foreclosure, where we lock ourselves into fixed narratives too early or for too long.

To evolve, we need mirrors. Honest feedback from trusted mentors, friends, or colleagues can offer blind-spot clarity and help expand our sense of self. At the same time, self-reflection practices like journaling, mindfulness, or even voice-memo reflection can deepen self-concept clarity and a stable, coherent understanding of who you are across time.

Treat identity as a draft, not a declaration, ask: What part of me is ready to be released? What values no longer fit?

This isn’t about erasing the past. It’s about consciously reauthoring the story of you.—Cory Muscara, author and former monk

3. Focus on Progress, Not Perfection

Nature doesn’t grow in straight lines, and neither do you. Progress is often irregular, nonlinear, and full of feedback loops. Instead of forcing a rigid plan, consider a fractal mindset: the idea that small, self-similar shifts across different areas of life can lead to exponential transformation.

This is how change works in the real world: through micro-adjustments.Shift your morning routine by five minutes. Reframe one piece of internal dialogue. Swap one unhelpful habit for something nourishing. Each act wires your brain for change, reinforcing the principle of neuroplasticity, that your brain is always capable of rewiring toward who you’re becoming.

Progress isn’t about having it all figured out. It’s about showing up, again and again, with just enough curiosity and courage to take the next small step.—Woody Allen, filmmaker

4. Expose Yourself to Controlled Discomfort

Just like in physical training, emotional resilience is built by repeated exposure to challenge, not all at once, but in small, deliberate doses. This controlled exposure is a principle rooted in cognitive-behavioral therapy, where gradual, repeated contact with discomfort rewires our response to stress.

Proactively shake up your routine: Disrupt yourself before the world does. With time, these intentional acts of discomfort increase your psychological flexibility and the ability to adapt, recover, and respond creatively under pressure.

But true growth isn’t just about leaving your comfort zone occasionally, it’s about disrupting patterns intentionally before life forces your hand. If you only stretch when circumstances demand it, you’re always in reaction mode. And that’s the real power of resilience.—Unknown

5. Cultivate Psychological Safety for Yourself

Transitions feel destabilizing because they disrupt our sense of control or our internal locus of control, the belief that we can influence our outcomes. When that center is shaken, it’s easy to feel unmoored. But discomfort doesn’t have to break you, it can become the raw material for reinvention.

Uncertainty, when approached with intention, becomes a laboratory for growth. Acknowledge your fears without giving them the microphone. This is the essence of cognitive reappraisal, the ability to reinterpret challenges in ways that empower rather than paralyze.

Treat your transition like an art project. Surround yourself with people who value growth over perfection. Learn to say no to misaligned obligations and protect your energy for what aligns with your evolving self.

What can you experiment with? Which constraints can be reframed as creative catalysts? The goal isn’t to eliminate uncertainty, it’s to become someone who thrives within it.—Viktor Frankl, neurologist and psychologist

The Competitive Advantage of Embracing Discomfort

The challenge is not to seek the easiest path but to identify the right kind of discomfort, the kind that fuels progress rather than paralyzing fear. It’s the discomfort that helps us grow as humans and challenges us with the fundamental question: What am I supposed to be learning from this experience?

Growth requires a mindset shift: challenges aren’t roadblocks, they’re signs we’re operating at our edge, where real development takes place. The “future you” isn’t a finished product; it’s a prototype in motion. Time spent in uncertainty, awkwardness, or even doubt isn’t a detour; it is the path forward.

The real question isn’t just Where do I want to go? But, am I willing to embrace the discomfort it takes to get there? When we do, today’s challenges become stepping stones.

True transformation begins not in mastering the present, but in daring to evolve into what’s next.—Søren Kierkegaard, philosopher and theologian.

TOPLEY’S TOP 10 May 12, 2025

Daily Top Ten No Comments

1. Chinese Stocks Erase Losses Since Liberation Day

Bloomberg

2. Japan ETF Breaks Out of Sideways Pattern

StockCharts

3. Foreign Investors Own 32% of Japan Stocks

According to the Tokyo Stock Exchange’s latest data, foreign investors now own 32% of Japan’s stock market, up sharply from 5% in the 1970s, while locals hold just 17%. And the gap might keep growing: as US stocks slumped amid tariff threats in April, foreign investors pumped a net $8.3 billion (¥1.2 trillion) into Japanese equities — a severe reversal from net outflows in the previous two months, per Japan Exchange Group.

Now, Japan is trying to lure its young, less trauma-ridden locals back into the market. The Tokyo Stock Exchange plans to lower the minimum investment threshold, aiming to make stocks more accessible, while the government expanded tax exemptions for retail investors last year. It’s also promoting financial literacy among millennials and Gen Zs.

All of this might be starting to pay off: according to the Investment Trusts Association, 36% of people in their 20s in Japan invested in mutual funds, stocks, and bonds last year, up nearly 3x from 2016.

Sherwood News

4. Short Interest in Stocks was Below Average 2020-2024…Got Back to Average on Tariffs

The Irrelevant Investor

5. Here is the Gold vs. U.S. Dollar Chart…Dollar Rallying on Chinese Trade Deal Today

yahoo!finance

6. Trump Exec Order to Lower Drug Prices…XLV will Open Below Long-Term 200 Week Moving Average….Next Support 2023 Levels

StockCharts

7. Where Can Younger Buyers Afford Homes?

NY Times

8. Washington DC Homes for Sale

Liz Ann Sonders

9. Wit and Wisdom from Warren Buffett

Via Ted Merz: Few people are as quotable as Warren Buffett.

I attended the Berkshire Hathaway annual meeting this weekend. It ended Saturday afternoon in dramatic fashion with the 94-year old money manager announcing he was stepping down after 60 years. The crowd gave him a standing ovation.

Before the bombshell announcement, Buffett spent four-and-a-half hours dropping wit and wisdom in a way only he can do.

I find that sometimes quotes convey the feeling from the room much better than a narrative article so I compiled a list of my favorites from the meeting.

It’s worth reminding readers that all of these comments came on the fly in response to specific questions from shareholders about business and life.

“People have emotions but you have to check them at the door when you invest.”

“The world is not going to adapt to you, you need to adapt to the world.”

“Everyone has setbacks, it’s part of life. You certainly have a setback when you die.”

“You get a few breaks in life in the people who you will meet. You need a handful of them. And when you have them, you treasure them.”

“Patience is not a constant asset or liability. You don’t want to be patient when the time comes to act.”

“If every time you swung you hit a homerun the game wouldn’t be very interesting.”

“Make the most of the people you meet who are going to make you a better person and forget about the rest frankly.”

“Every now and again you get an extraordinary opportunity. Most of the time you don’t have much of an edge.”

“If you are in something in which you are going to lose you should quit.”

“We are not in the business of solving unsolvable problems.”

“Don’t take a position on anything unless you can argue the opposite just as well.”

“Values change and they don’t always change upward.”

“If you need lots of money you should probably behave in a way that encourages them to give you money.”

“I was born in 1930 and things got much more attractive over the next two years and I didn’t do anything about it. That was the opportunity of a lifetime and I blew it by worrying about the kid in the next crib.”

“If Berkshire went down 50 percent I would regard that as a fantastic opportunity.”

“I don’t get fearful the way other people are afraid in a financial way.”

“It’s not that I don’t have emotions, but I don’t have emotions about the price of stocks.”

“It’s always better to make a lot of money without putting up capital.”

“You can’t blame humans for behaving like humans but you should understand their motivations.”

“Look around to see what interests you. I wouldn’t try to be someone else.”

“You can’t say the system is a failure but you can say it’s very difficult to make major changes.”

“It’s easier for an organization to see its quality go downward than upward.”

“I’ve already told you more than I know so let’s move on.”

10. Nine Soft Skills for Career

Ben Meer

TOPLEY’S TOP 10 May 09, 2025

Daily Top Ten No Comments

1. Buybacks in Last Month $518bn — the biggest rolling three-month sum on record, FT reports

FT.com

2. Last Month was Fewest American M&A Deals Since 2009

Reuters.com

3. Ethereum Bounces 40% Off Lows

The Market Ear

4. Bitcoin ETF Making Run at Highs

Stock Charts

5. Trump’s crypto dealings are jeopardizing a bipartisan stablecoin bill

By Filip De Mott for Business Insider

President Donald Trump’s crypto ventures are getting in the way of his own agenda.

The fate of a bipartisan stablecoin bill has fallen into doubt as congressional Democrats show frustration with the president’s crypto moves.

The so-called GENIUS Act, once considered a quick win for the industry, is now losing support on one side of the aisle.

Pushback has grown as Trump and his family dabble in a range of crypto endeavors.

These include the issuance of his own meme coin before his inauguration, involvement in a new stablecoin, a possible family stake in Binance, and a partnership between the Trump Media & Technology Group and crypto.com.

6. India vs. Pakistan Military Size

Daily shot Brief

7. China to Vietnam to U.S. Trade Route

Reuters

8. U.S. Automakers are Huge Importers

Liz Ann Sonders

9. 50% of World in Poverty to 10%

Peter Mallouk

10. Opinion: 7 life lessons from Warren Buffett that have nothing to do with picking stocks

Via MarketWatch

We all have the ability to emulate the Oracle of Omaha in the ways that really matter By Brett Arends

I’ve been following Buffett and writing about him for a quarter-century, which is long by some measures and no time at all by others. (He has been managing money for nearly three times that long.) Now that he has announced, at age 94, that he is at last retiring as CEO of Berkshire Hathaway, there are all the usual encomia about his investment genius and his stock-picking skills. And those are extraordinary, no question: It is very unlikely we would see his like again, even if we lived 10 lifetimes.

But it’s all the other stuff that has really struck me over the years — the smart decisions about life and money he’s made that don’t get so much attention. And that’s a pity, because those who try to replicate Buffett’s investment success probably won’t succeed. But everyone can learn from the other stuff.

1. He never moved to New York. Buffett never left Omaha, Neb., where the cost of living is a fraction of New York City and the quality of life, for him and probably for most people, is going to be much higher. (Bankrate reckons the cost of living in Omaha is 60% below that in Manhattan — meaning someone in Omaha need only earn $40,000 a year to have the same standard of living of someone in New York with an income of $100,000.)

Compare and contrast with all those people paying through the nose to live in a nice home in an expensive locale, or living in a shoebox, or spending 90 minutes commuting each way. Employers are now pushing everyone back to the office. Fair enough. But how about if more employers moved their offices somewhere more livable and affordable? It’s not the office that workers hate so much as the commute.

2. He didn’t waste money on stuff. Not for him the yachts, expensive cars, luxury properties or other toys of the rich and bored. Buffett seemed to understand early and instinctively what it has taken psychologists decades to conclude: That beyond a certain level, more spending will add little or nothing to your happiness. (When giving away his money, he said that spending beyond about 1% of his net worth on himself and his family would add nothing to their well-being or happiness.)

Psychologists refer to “the hedonic treadmill.” This is the futility — hence “treadmill” — of trying to achieve happiness by constantly buying more and bigger and better stuff.

The problem is that the human brain adapts to whatever we have. We get used to it. This is why lottery winners typically end up no happier years later than anyone else, and why if you visit a place where really rich people hang out — Palm Beach, Fla., or a five-star luxury hotel — and look around, you probably won’t see them all grinning madly about the fact that they are rich and marveling at all the things they can afford. But while “stuff” is costly to the rich, it’s lethal to the rest of us: That’s money we will need. The only way to beat the treadmill is to get off it.

3. He has a job he loves. From a financial standpoint, Buffett hasn’t had to work since he was in his 40s, but he kept going for another half-century — and loved it. “I’ve always worked in a job I love,” he once said. “I loved it just as much when it was a big deal if I made a thousand bucks, and I urge you to work in jobs you love.” Another time he described his job more as “play” than “work.”

This is priceless advice. Most of us will spend most of our waking hours, for the bulk of our lives, either working, traveling to or from work, getting ready for work or recovering from it. What is the dollar value of that time? It was a wise person who first observed that if you do a job you love, you’ll never work a day in your life.

Tailor your MarketWatch experience to your needs. Update your interests to help us recommend the most relevant MarketWatch features to you.

4. He has given, and is continuing to give, most of his money away. It’s almost impossible to imagine all the good that will be achieved with the hundreds of billions of dollars that Buffett has accumulated during his lifetime and that he is giving away to good causes. “Were we to use more than 1% of my claim checks (Berkshire Hathaway stock certificates) on ourselves,” he writes, “neither our happiness nor our well-being would be enhanced. In contrast, that remaining 99% can have a huge effect on the health and welfare of others.”

5. He didn’t care what the crowd thought. After more than a quarter of a century of writing about markets and finance, I’ve come to think my main expertise — possibly my only expertise — is on the subject of “popular delusions and the madness of crowds.” From ancient Greece to the COVID-19 crisis, it’s a subject that has fascinated me. And learning about it has made me especially fond of Buffett.

It wasn’t only during the dot-com bubble that he stood against the crowd’s insanity. He closed down his first partnership in the 1960s rather than join in the bubble of the “go-go years.” He invested, and publicly urged others to invest, during the epic bear market of the 1970s. He did it again during the 2008 crash. He made his money by courageously standing up against mass insanity and sticking to his principles. Bravo.

6. He’s humble. I’ve always said I don’t trust anyone until I have heard them say “I don’t know” and “I was wrong.” Buffett’s willingness to do both has been among his greatest and most profitable attributes. He has frequently emphasized that he invests only within his “circle of competence,” meaning he only invests in what he knows. And he admits there is a lot he doesn’t know.

“During the 2019-23 period, I have used the words “mistake” or “error” 16 times in my letters to you,” he wrote to stockholders in the 2024 Berkshire Hathaway annual report. “Many other huge companies have never used either word over that span.” For them, he added, “it has generally been happy talk and pictures.”

7. He’s acted like a grown-up. Can you imagine Warren Buffett standing around on a stage (in a graphic T-shirt) waving a chainsaw in the air and laughing about the middle-class jobs he was going to eliminate? Can you imagine him bragging about using bankruptcy laws to stiff his creditors? Can you imagine him running a bank so recklessly that it would end up crashing the global economy, but cashing out of his own stock before the stuff hit the fan, and then walking away with a shrug? I can’t. But I’ve seen billionaires and Wall Street tycoons do exactly those things in the recent past.

If you want to see how a billionaire should behave — in my view, anyway — watch Buffett’s remarkable statement to Congress during the Salomon Brothers hearings in 1991. There are billionaires, and then there are billionaires. We have too many of one kind, and too few of the other.

TOPLEY’S TOP 10 May 07, 2025

Daily Top Ten No Comments

1. Mag 7 Revenues and EPS at Record Highs…Not Dead Yet

Mag 7 vs. SPX. The Mag-7’s forward revenues and forward earnings share both are at new record highs of 11.8% and 22.6%.

Yardeni Quick Takes

2. S&P Ex-NVDA Trails Japan and Europe Since 2022

The Irrelevant Investor

3. VIX Volatility Index -50% in One Month

StockCharts

4. Valuations Back to Highs

Bloomberg

5. U.S. GDP Growth Turns Negative

yahoo!finance

6. Private Equity Distributions 11% vs. Average 25%

Bloomberg

7. Import Surge of Pharmaceuticals

Michael McDonough

8. Monthly Payment for Mortgage Doubled in Last 5 Years

The biggest constraint continues to be affordability, with the median housing payment needed to afford the median priced home nearly doubling over the past five years.

Charlie Bilello

9. Money Pours into American Soccer

More money is pouring into US soccer as the sport’s popularity grows in the country. Sponsorship revenue for Major League Soccer is up more than 10% so far this year compared to 2024, CNBC reported, alongside a surge in ticket and merch sales; much of that is owed to Argentinian superstar Lionel Messi joining Inter Miami in 2023. Newfound corporate support — coupled with next year’s men’s World Cup in North America — bodes well for soccer’s future in the US, an expert wrote in Sports Business Journal: American clubs still pale financially in comparison to the European giants, but “a perfect storm exists for one of the world’s oldest sports to reach a new zenith of popularity.”

Semafor

10. Face the Criticism (The Daily Stoic)

Marcus Aurelius was the public face of an empire. Seneca published plays and books. Cato and Cicero ran for office. Epictetus was a slave to a powerful Roman, at his whim and his mercy.

In other words, they knew what it was like to be criticized. They knew what it was like to be received warmly by the audience…and not so warmly. They were subject to withering abuse, talked about as if they were not standing right there or as if they didn’t have normal human feelings.

But of course they did.

So what Stoicism aimed to help them with was enduring the pains and blows of feedback and critique and attack. “If only they really knew me,” Epictetus once joked, “they say even worse things!” This was his way of making light of the cruel things he would have often heard from his abusive owner. “We care about ourselves more than other people,” Marcus Aurelius writes with bafflement in Meditations, “but care about other people’s opinions more than our own.” In another passage, he reminds himself to consider the character and the habits of the person attacking him—thinking about what they were doing in private just a few minutes ago.

These public-facing Stoics would have loved the response of the Canadian Prime Minister Pierre Trudeau when he was told that Richard Nixon had called him an “asshole.” “I have been called worse things by better people,” he said with a shrug.

Being criticized is part of the job—any and every job. So is being misunderstood. Being abused isn’t fair…but no one gets out of life without experiencing some share of it.

We have to be ready for it…and ready to put it in its proper context. We have to be ready to shrug it off…and count ourselves as lucky that it wasn’t worse. Because it always can be!

TOPLEY’S TOP 10 May 06, 2025

Daily Top Ten No Comments

1. Pre and Post Liberation Day Sector Returns

Fundstrat

2. Nine-Day S&P Win Streak a 99th Percentile Event

DorseyWright

3. U.S. Dollar Chart-#1 to Watch 2025…Hit First Level of Support

StockCharts

4. Amazon Rally Stops Below 200-Day

StockCharts

5. No Slowdown in AI Captial Spending with Amazon Posting Biggest Projected Number

VettaFi

6. The Updated Chart—Exit from Mutual Funds to ETFs

Investment Company Institute

7. China Exempts 25% of American Imports from Tariffs

Bloomberg

8. Student Loan Data

Axios

9. Warren Buffett’s Rules

Dave Ahern

10. Ever experienced a headache from drinking red wine? Researchers may have identified a reason

Quercetin, a bioactive flavonoid present in red wine, can impair alcohol metabolism.

Via Peter Attia: While many of us enjoy a few alcoholic beverages with friends and family now and then, the consequences of overindulgence are famously unpleasant. Headache, nausea, fatigue, and general malaise are commonly experienced by over-imbibers and can be temporarily debilitating. The post-consumption headache is particularly common, but many find that not all sources of alcohol are equally likely to result in this symptom. Red wine, in particular, is notorious for inducing headaches and does so roughly 3-fold more frequently than other beverages,1 often within 30 minutes and after only a single glass.

But what might explain such an effect? One study suggests that the polyphenol quercetin, a biologically active molecule present at relatively high concentrations in red wine, might be responsible.2

What causes alcohol-related headaches?

Alcohol (or more precisely, ethanol, the type of alcohol present in alcoholic beverages) has direct effects on many physiological systems and is responsible for the “buzz” sensations people experience when drinking. However, the metabolism of alcohol involves production of an intermediate compound known as acetaldehyde, and it is the build up of acetaldehyde that appears to induce the unpleasant side effects of alcoholic beverages.

Production of acetaldehyde is the first step in alcohol metabolism, after which this intermediate compound is further metabolized by the enzyme acetaldehyde dehydrogenase (ALDH) into harmless end-products. Slowing the rate of this second step can therefore lead to accumulation of acetaldehyde and the consequent headaches and other negative sensations associated with alcohol intake.

Indeed, the strongest evidence of acetaldehydes’ culpability in the undesirable effects of alcohol overconsumption comes from studies of individuals with a genetic defect in the ALDH2 gene. Those with a homozygous ALDH2 defect demonstrate almost no ALDH2 activity, and subsequently experience greatly increased acetaldehyde levels following even moderate alcohol consumption.3 Similarly, suppression of ALDH2 by the drug disulfiram also leads to increased serum acetaldehyde. Importantly, the undesirable effects of alcohol consumption, including headache, are highly prevalent in both those with ALDH2 defects and those taking disulfiram.4

But some data5 suggest that ALDH2 activity may also be impaired by quercetin, a biologically active flavonoid compound found in high levels in red wine. Red wine contains roughly 10-100 times higher concentrations of quercetin than beer, white wine, or spirits,6 so if the suppression of ALDH2 by quercetin is sufficient to significantly raise serum acetaldehyde levels, this might easily explain why undesirable effects seem more pronounced with red wine relative to other sources of alcohol. Investigators Devi et al. thus sought to determine the magnitude of the specific effects of quercetin on ALDH2 activity.

What they did

This study was designed to assess the ability of quercetin and its metabolites to affect the activity of ALDH2. To accomplish this, the researchers utilized an in vitro biochemical assay in which quercetin or related compounds were added to a solution containing human ALDH2 enzyme, and enzyme inhibition was measured by spectroscopy.

Quercetin at a concentration of 20 μM was found to inhibit ALDH2 by 28%, but in addition to this direct effect of quercetin itself, a major metabolite of quercetin — quercetin-3-glucuronide (Q3G) — caused an astounding ~78% inhibition of ALDH2. The IC-50 (the concentration of a substance required to reduce a biological process by half its maximal value) for quercetin and Q3G was calculated to be 26.5 μM and 9.6 μM, respectively. (For reference, the IC-50 of the ALDH2 inhibitor disulfiram was calculated to be 1.45 μM, indicating a stronger inhibitory effect by disulfiram than either quercetin or Q3G.)

Based on reports that quercetin is present in red wine at a concentration of about 50 μM and that most quercetin that reaches circulation is converted to Q3G, the authors calculated that consumption of a 150-ml glass of red wine would lead to serum Q3G concentrations of approximately 5 μM (out of a total quercetin concentration of ~6 μM). Given the findings of their in vitro tests, they then estimated that this amount of Q3G would impair ALDH2 activity by ~37%.

Interpreting these data

Though this study was well executed, its results only go so far. The use of an in vitro model, in which reagents are simply added together in a test tube, certainly presents a limitation to extrapolating these data to humans. When humans consume quercetin-containing food or drink, it must first be absorbed by the gastrointestinal tract and undergo first-pass metabolism by the liver before reaching circulation. What is the ultimate bioavailability of oral quercetin? The source (many vegetables and herbs contain quercetin, particularly capers, dill, fennel, and onions), presence of other macronutrients, and interindividual variation all appear to significantly impact absorption.7 Indeed, studies measuring serum quercetin levels after wine consumption have reported highly variable results, and although the 6 μM concentration estimated by Devi et al. does fall within reported ranges, it’s important to keep in mind that this was an estimate — they performed no in vivo experiments to actually measure the resulting quercetin concentrations.

This brings us to another noteworthy caveat, which is that these experiments also did not attempt to determine the effect of 37% ALDH2 inhibition on acetaldehyde build-up — the key variable in assessing whether ALDH2 inhibition by quercetin might translate to noticeable differences in the negative symptoms of alcohol intake. (Again, this is weaker inhibition than is seen with disulfiram, which is known to have a very strong effect on alcohol-related side effects.) While it is possible that red wine consumption could increase serum quercetin metabolite concentrations high enough to significantly impact ALDH2 activity and therefore increase serum acetaldehyde to a level sufficient to induce a headache, Devi et al. demonstrate only one isolated link in this chain of events — albeit a critical one for which we had the least prior evidence. No study has yet attempted to simultaneously measure all of these variables, let alone in human subjects.

Can you enjoy red wine but avoid the headache?

Still, if we assume these results reflect a genuine, significant pathway underlying the dreaded “red wine headache,” does this mean that you can never enjoy a cabernet or merlot without pain? Not exactly, as various strategies exist for mitigating the headache-inducing effects.

The simplest approaches are old standbys: drink less in total, make sure to consume plenty of water while drinking wine, and extend the consumption window to allow more time for acetaldehyde metabolism to occur and prevent it from building up in the blood. But wines also vary significantly in their quercetin content. White wines and rosés contain far less quercetin than reds, and even among reds, some varieties and vintages will have higher or lower levels than others. (In fact, some winemakers take intentional steps to reduce quercetin content through filtration and fining agents during the winemaking process, as quercetin tends to cause precipitates to form in wine.) Choosing a variety with a low level of quercetin may be advantageous, though this can be challenging since factors such as soil properties and sun exposure — which can change from year to year and aren’t generally disclosed on a bottle’s label — can have substantial impacts.

Unfortunately, these mitigation strategies don’t apply universally. If you happen to carry two copies of a defective ALDH gene (common for those of East Asian descent) and experience symptoms after any alcohol consumption, it is unlikely any of these approaches will provide much relief. Further, if quercetin contributes to headaches with red wine, it may not be the only factor that does so. Some individuals find that at-home wine filters, which remove many sulfites and histamines but do not affect quercetin, help to prevent wine-related headaches, suggesting that these other molecules play a role in generating this particular symptom. Finally, we must emphasize that these strategies might prevent the short-term negative effects of alcohol, but, with the exception of reducing total intake, we have no evidence that they would reduce alcohol’s numerous long-term negative effects on health.

The bottom line

Devi et al. identified a plausible mechanism to explain the headache and hangover symptoms commonly experienced by red wine drinkers. A study using human subjects and simultaneously measuring the quercetin content of alcoholic beverages, serum acetaldehyde, serum quercetin content following consumption, and the presence and severity of headache and hangover symptoms would help confirm the proposed links between red wine and headaches, though there would still exist some possibility that quercetin is not the only culprit.

In the meantime, those who wish to enjoy wine without the headache might try various mitigation strategies to lessen symptoms, but of course, the surest strategy — and the one that is best for long-term health, as well — is to reduce overall intake.