rewrite this title Alcohol and Cancer, Sugary Drinks and Diabetes, and Ketamine and Depression

Let’s get the COVID news over with. It’s not gone, but it’s diminishing. For example, the hospitalization and death rates have dropped by a major percentage during the past year. At the end of 2023, the hospitalization rate in the US was 7.8 per 100,000 population. Almost a year later, in mid December 2024, that rate had dropped by three-quarters, to 2.6 per 100,000 population. The COVID death rate has declined similarly, from a total of 2,364 per week as of 20 January 2024, to 445 per week as of 11 January 2025. And, just to emphasize the scope of the total drop in the weekly COVID death rate, at its peak as of January 9, 2021, COVID took the lives of an estimated 25,974 persons in the US. The most recent rate, according to my calculation, is about 0.17% of the peak rate. Not gone, but greatly diminishing.

So, what is there to worry about? Some public health experts specifically point to elevated levels of the coronavirus in waste water. The finding comes from measurements of the virus found in the CDC’s National Wastewater Surveillance System. An increase in virus activity in wastewater nationwide for the week ending December 14, having risen to a moderate level, up from a low level the week before, suggests an increased risk of infection, the CDC says. Twenty-one states – more than 40% – have high or very high levels of COVID virus in the wastewater.

Noah Greenspan, program director of the Pulmonary Wellness & Rehabilitation Center in New York City, observed that this shouldn’t be a surprise and it’s likely the CDC would also find increased levels of pneumonia and respiratory syncytial virus (RSV) in wastewater.

But it comes at the time of year when people may not as careful as they need to be to keep themselves safe. Greenspan pointed out that “At a time when people are spending more time indoors, attending holiday events and gatherings, and there is an increase in circulating pathogens, people really need to take precautions if they don’t want to get sick.”

Michael Hoerger, a public health expert at Tulane University School of Medicine who tracks COVID-19 trends, stated in a December 16th post that based on previous COVID pandemic waves, the wastewater findings suggest the country is now heading into a large winter wave. He estimated that one in 64 persons in the US is actively infectious. He commented that the current COVID situation should be taken seriously, suggesting that there is a one in eight chance of exposure in a family gathering of 10 people if none of those individuals is testing or isolating. He added that “This is a very risky time in terms of lots of people interacting indoors, so we don’t really know how quickly transmission can pick up.”

Levels of the coronavirus in wastewater increased in three regions (Northeast, Midwest, and South) during the week ending December 14th. These levels declined slightly in the West from the week ending December 7th to the week ending December 14th, according to the CDC.

Northeast: Overall, levels were low, although New Hampshire registered as very high.
Midwest: This region registers as high, up from moderate. Missouri and South Dakota registered very high levels of the coronavirus in wastewater; however, reporting coverage in those states was limited.
South: Coronavirus levels increased slightly, but remained fairly low.
West: Overall, levels in this region fell slightly and remain low. New Mexico was an exception, with very high coronavirus levels in wastewater.

I report those statements from public health officials with a modicum of skepticism. Public health officials are duty bound to be on the alert to any threats to the health of the public, of course, but the actual figures that we’re seeing regarding hospitalizations and deaths should be reassuring. The data about levels of the COVID-causing coronavirus are certainly of interest, but the actual numbers of COVID cases resulting in hospitalization or mortality are very low, as pointed out above. The numbers of cases of infection not resulting in hospitalization or death are exceedingly difficult to estimate with a reasonable degree of confidence, but if the huge decline in those more serious cases is any indication, the numbers of less serious cases must also have greatly diminished.

Even though coronavirus levels of wastewater in New Hampshire were classified as “very high” as of mid-December 2024, that does not seem to be reflected in the actual numbers of reported cases. The most recent statistics for New Hampshire were for the week ending April 27, 2024, when there was one reported new case for every 100,000 population. This compares with a case rate of 31.3 new cases per 100,000 population as of January 18, 2022. The number or unreported new cases is certainly higher, but the general trend is unmistakable. COVID is not gone, but much, much less of a threat than it was.

Moderate alcohol consumption or teetotalitarianism – which?

A polite quarrel looms. A December review from the National Academy of Sciences, Engineering, and Medicine restated the hypothesis that moderate drinking has a number of benefits. Specifically, this august body stated that moderate drinkers generally experience fewer fatalities from heart attacks and strokes and a lower overall death rate than persons who never partake of alcoholic beverages.

This perspective has been opposed by several other august bodies, such as the National Cancer Institute and the World Health Organization.

The argument has been going on for centuries. Back in the 18th century, an English physician wrote an essay in which he claimed that moderate drinkers lived longer than either drunkards or total abstainers. He described moderate drinking as perhaps a glass of sherry before dinner, some wine with dinner, and a nip of brandy after dinner. He contrasted this with the drunkards, who went to the pub and got totally wasted on large quantities of beer or whiskey, and also with the teetotalers. Neither the drunkards nor the teetotalers lived as long as the moderate imbibers, or so this doctor claimed.

His claims were promptly rebutted on the grounds that his moderate drinkers came from a comfortably well-off sector of society, whereas the drunkards and the teetotalers were more apt to be poor manual laborers who perished at younger ages due to natural causes from which the well-off were more likely to be shielded.

The same general picture persists to the present. There have been many studies reporting what is labeled as an inverse association between moderate alcohol consumption and the risk of death from a range of cardiovascular causes, meaning that moderate drinking lowers – not raises! – the risk of death from those causes. These studies were, of course, not randomized, placebo-controlled studies, but based on self-report. Which is to say, persons were asked whether they partook of alcoholic beverages, and, if they did, how much. These responses would then be compared with data from healthcare providers, who presumably had reliable information as to survival. Based on this data, the healthcare system can draw conclusions about the relationship between alcohol consumption and survival, and these conclusions should be reliable.

But, as with the conclusions of that English physician back in the 18th century, other factors certainly come into play. Self-reported moderate drinkers are probably more careful in general about their health than heavy drinkers. They probably see their healthcare providers more regularly and follow their guidance. So the benefits that are reported may be due to difference in lifestyle more than to the specific effects of alcohol on the human physiology.

A paper from the Harvard T.H. Chan School of Public Health has the following to say on this contentious subject:

“The idea that moderate drinking protects against cardiovascular disease makes sense biologically and scientifically. Moderate amounts of alcohol raise levels of high-density lipoprotein (HDL, or “good” cholesterol), and higher HDL levels are associated with greater protection against heart disease. Moderate alcohol consumption has also been linked with beneficial changes ranging from better sensitivity to insulin to improvements in factors that influence blood clotting, such as tissue type plasminogen activator, fibrinogen, clotting factor VII, and von Willebrand factor. Such changes would tend to prevent the formation of small blood clots that can block arteries in the heart, neck, and brain, the ultimate cause of many heart attacks and the most common kind of stroke.  (https://nutritionsource.hsph. harvard.edu/healthy-drinks/drinks-to-consume-in-moderation/alcohol-full-story/)

So, there is some genuine scientific evidence supporting the premise that moderate alcohol consumption conveys benefits in terms of heart health. This position will be reiterated in the next edition of the U. S. Dietary Guidelines. This is based on an evidence review, by the National Academy of Sciences, Engineering, and Medicine, which is soon to be published.

However, the U.S. Surgeon General, Dr Vivek Murthy made a public statement on Friday, January 3rd, sharply contesting the view that alcohol had any health benefits whatever. He focused his comments specifically on the link between alcohol consumption and the risks of cancer, stating that alcohol directly contributes to 100,000 cancer cases and 20,000 related deaths per year, not addressing the evidence that alcohol had protective effects in terms of cardiovascular disease.

He noted that the absolute risk of breast cancer over a woman’s life span is about 11.3% for those who have less than one drink per week. That risk increases to 13.1% for women who have one drink per day and to 15.3% for those who have two drinks per day. For men, the absolute life-time risk of developing any cancer increases from about 10% for teetotalers to 11.4% for the one-drink-per-day group and to 13% for the group that has two drinks per day on average.

Dr Murthy observed that alcohol was the third leading preventable cause of cancer, after tobacco and obesity. He was quoted in the NYTimes as follows:

“I wish we had a magic cutoff we could tell people is safe. What we do know is that less is better when it comes to reducing your cancer risk. If an individual drinks occasionally for a special event, or if you’re drinking a drink or two a week, your risk is likely to be significantly less than if you’re drinking every day.”

So, as regards heart disease risks, no clear answer from Dr Murthy, who did not address any possible connection between alcohol and heart disease. Speaking as a moderate imbiber, I’m not terribly concerned about that at-most 3% increase in my life-time cancer risk related to my life-long practice of wine with dinner. And I wonder whether the cardiac benefits, which Dr Murthy ignores, may to some degree compensate for that small increase.

I also can’t help but wonder whether the emphasis on the association between drinking alcoholic beverages and health risk may be colored, to some degree, by underlying religious or moral views. Prohibition, as we remember, was instituted not to improve our health, but to mend our sinful ways.

And, as has been abundantly noted in these missives as well as elsewhere, wine is an elemental component of the Mediterranean diet, which has been linked to health benefits and longevity. The contrarian voices will rapidly proclaim that those benefits are conveyed by resveratrol, which is present in red wine only, and have nothing to do with alcohol. However, the benefits of the Mediterranean diet are surely not limited to meals accompanied by red wine. Fish and chicken, for example, are accompanied by white wine in the Mediterranean diet, and that does not adversely affect the benefits of the Mediterranean diet.

As I said at the start of this section, it is a polite quarrel. I don’t see a truce on the horizon.

Sugary drinks are linked to a global increase in diabetes and heart disease

A study, published online in Nature Medicine on January 6th. estimates that 2.2 million new cases of type 2 diabetes and 1.2 million new cases of cardiovascular disease occur each year globally due to consumption of sugar-sweetened beverages.

In developing countries, the case count is particularly sobering. In Sub-Saharan Africa, the study found that sugar-sweetened beverages contributed to more than 21% of all new diabetes cases. In Latin America and the Caribbean, they contributed to nearly 24% of new diabetes cases and more than 11% of new cases of cardiovascular disease.

Colombia, Mexico, and South Africa are countries that have been particularly hard hit.   More than 48% of all new diabetes cases in Colombia were attributable to consumption of sugary drinks. Nearly one third of all new diabetes cases in Mexico were linked to sugary drink consumption. In South Africa, 27.6% of new diabetes cases and 14.6% of cardiovascular disease cases were attributable to sugary drink consumption.

The reason sugary soda-pop is a specific menace has been evident for some time. In contrast with sugar-sweetened comestibles, sugary drinks mostly do not pass from the stomach into the intestines, which is what happens with comestibles. When we eat a nice slice of apple pie, we digest the foodstuffs in the pie, extract the sugar and use it for energy. Actually, we convert a lot of the food, especially carbohydrates, into sucrose and use it for energy.

This does not happen with sugar in sugary soft drinks. Instead, the sugar – immediately converted to sucrose – quickly goes into the bloodstream, where it has the potential to cause significant problems. Our mechanism for converting sucrose into energy depends on the secretion on insulin, which comes from a section of the pancreas called the islets of Langerhans. There are several categories of cells in these islets, some of which release insulin. Insulin is the hormone that stimulates the glucose uptake by our muscle tissue. Glucose is the fuel that keeps our muscles and other body parts running, and insulin is what triggers those tissues to absorb the sucrose and do their jobs.

But when there is too much glucose in our bloodstream, it puts a strain on those islet cells. They get fatigued and don’t do their jobs as effectively. What this leads to is an excess of sucrose in the bloodstream, i.e., diabetes, specifically, type 2 diabetes mellitus, or T2DM as it is commonly abbreviated. And the consequences of diabetes can be very serious, including damage to the heart itself and damage to the blood vessels. A common result of untreated T2DM is deterioration of the circulatory system in the extremities, especially of the lower legs and feet. This can lead to amputation.

People in the US and in Europe do drink a lot of sugary soda-pop, but the well-off and well-educated classes are more likely to shun sugary soda-pop that their less well-off well-educated brethren. A New York City study several years ago found that within Harlem, diet soda was more likely to be the drink of choice in the higher rent neighborhoods. In a way, the choice of sugary soda-pop makes a certain amount of sense. You’re paying money, you may as well get some calories out of it. The sugar feels good. Worries about your health get pushed away.

So the consumption of sugary soda-pop is one more instance of the lifestyle habits of the less well-off and less well-educated that contribute to health problems. In the past decades we have seen a significant decline in the fraction of tobacco smokers in the population of the more developed parts of the world. Perhaps in the coming years there will be a similar decline in the consumption of sugary soft drinks.

The global prevalence of diabetes has greatly increased, but it is undertreated

This is based on a pooled analysis of 1,108 population-based studies with 141 million participants, published in Lancet on November 23, 2024. (Lancet 404;10467,pp2077-2093).

The findings in this study were, in my opinion, nothing short of shocking. In 2022, according to these studies, an estimated 828 million persons over the age of 18 had diabetes. This represents an increase of 630 million over the 198 million estimated for 1990, which means that if those figures are correct, the number of persons with diabetes were 4.3 times higher in 2022 than in 1990. Those figures are based on a very large number of separate studies with different criteria for determining the number of individuals with diabetes, and Lancet offers no qualifying comments on the validity of those figures. But, no matter how you slice it, it certainly seems that the increase in the prevalence of diabetes is huge.

According to their meta-analysis, the prevalence of diabetes in women increased in 131 countries, and the prevalence in men increased in 155 countries. The largest increases were in low-income and middle-income countries in southeast Asia (e.g., Malaysia), South Asia (e.g., Pakistan), the Middle East and North Africa (e.g., Egypt), and Latin America and the Caribbean (e.g., Jamaica, Trinidad and Tobago, and Costa Rica).

This steep increase in the prevalence of diabetes reminds me of a similarly steep and rapid increase in the prevalence of obesity among Navajos in Arizona. The link, and the highly likely cause, was the coming of several fast-food franchises to the Navajo reservation. Before the arrival of those places, the residents of the reservation relied on whatever food they could raise on their arid land, much as their ancestors had for centuries. But when the fast-food places turned up, obesity came quickly.

The lowest prevalence of diabetes in the world in 2022 was in Western Europe and East Africa for both sexes, and in Japan and Canada for women. The highest prevalence in the world in 2022 was in countries in Polynesia and Micronesia, some countries in the Caribbean and the Middle East and north Africa, as well as Pakistan and Malaysia.

Another disturbing statistic from this meta-analysis is that in 2022, 445 million adults aged 30 years or older with diabetes with diabetes did not receive any form of treatment. This figure was estimated to be three to five times greater than the number of untreated adults with diabetes in 1990. That is despite the estimate that diabetes treatment for women increased in 118 countries, and for men in 98 countries. Based on these figures, it seems abundantly clear – at least, according to the estimates – that most of the new cases of diabetes since 1990 are not being treated.

The largest improvement in treatment coverage was in some countries from central and western Europe and Latin America, Canada, South Korea, Russia, Seychelles, and Jordan. There was no increase in treatment coverage in most countries in sub-Saharan Africa, the Caribbean, Pacific island nations, and south, southeast, and central Asia. In 2022, treatment coverage was lowest in countries in sub-Saharan Africa and south Asia, and treatment coverage was less than 10% in some African countries. Treatment coverage was 55% or higher in South Korea, many high-income western countries, and some countries in central and eastern Europe, Latin America, and the Middle East and north Africa.

Based on the statistics quoted in Lancet, it certainly appears that in most countries, especially in low-income and middle-income countries, diabetes treatment has not increased at all or has not increased sufficiently in comparison with the rise in prevalence. The burden of diabetes and untreated diabetes is increasingly borne by low-income and middle-income countries. This is not unexpected, and it is certainly the case that most diseases affect lower-income populations disproportionately.

However, diabetes is a serious threat in that it can lead to major complications, as we have noted, such as amputation, loss of vision, and kidney failure. And treatment of diabetes is neither expensive nor complicated. Non-insulin-dependent persons with diabetes can usually manage that disease with metformin, which is neither rare nor expensive. Of course, many persons with diabetes live in areas where medical care of any kind is difficult to access, and there is no convenient pharmacy where they can just walk in and pick up a package of metformin. But diabetes is a neglected target for healthcare systems. If a treatment coverage percentage of 55% is considered “high” in high-income western countries, that, in my view, is evidence of a failure in the healthcare systems in those countries.

There is no rational alibi for the undertreatment of diabetes in nations that can easily afford to keep this disease under control.

Ketamine for depression: might be risky. but for some persons, it’s what works

This update is based on a November report in Harvard Health about the program at the Ketamine Clinic for Depression at Massachusetts General Hospital. Many of the clinic’s patients have not been helped by traditional treatments, including psychological counseling, antidepressant medication, transcranial magnetic stimulation, and electroconvulsive therapy. The clinic’s founder and director, Cristina Cusin, says that with its rapid antidepressant effects, ketamine is sometimes the only option that provides relief. It by no means provides a permanent or lasting cure for depression – just temporary relief. Thus, ketamine injections are administered periodically, based on need.

Ketamine was first used in Belgium in the 1960s as an anaesthesic for animals. The FDA approved it as an anaesthetic for humans in 1970. It was used in the treatment of injured soldiers on the battlefields in the Vietnam War.

Ketamine as a treatment for depression is a totally different story. Depression is a mental health disorder, characterized by feelings of sadness and hopelessness, which affects 18% of Americans. One-third of those diagnosed with depression don’t respond to standard treatments, with acute consequences to their personal and professional lives. The stigma associated with depression makes it harder for people to seek treatment.

“We don’t have good weapons to treat some severe forms of depression, just like we don’t have treatments for advanced-stage cancer,” said Dr Cusin, who is also an associate professor in psychiatry at Harvard Medical School. “We’re always looking for the next thing so that we can continue to offer hope to patients who don’t respond to standard treatments.”“In our society, if you suffer from depression, you may be told to ‘try harder,’ ‘stop complaining,’ ‘pick yourself up by your bootstraps,’ and so on. But there are some forms of depression that have a strong biological component; there are neurocircuits in the brain that are not functioning right. In many cases, it’s not for lack of trying.”

Patients must follow a strict protocol in order to be admitted to the MGH Ketamine Clinic. Not only do they have to be referred by their primary prescribers, but they must also have received prior treatments for depression that did not have the desired outcomes. At the Ketamine clinic, therapy is integrated with other treatments and is done in the clinic under medical supervision and in coordination with patients’ primary medical teams. The clinic does not admit self-referred patients or those with active substance use disorders or a history of psychosis. Ketamine produces hallucinogenic effects and dissociation, which can exacerbate psychotic symptoms.

Other risks associated with ketamine are the possibility of developing addiction, as well as several other medical problems. Low doses of ketamine can result in problems with attention, learning ability, and memory. In high doses, ketamine can cause delirium or extreme confusion, memory loss, problems with physical movement, high blood pressure, and depression. There is also a very small chance of breathing problems that can be fatal.

However, for some patients who experience rapid relief from their symptoms of depression after treatment, ketamine is a game-changer. Dr Cusin said, “Our patients have failed other treatments, so they don’t have a lot of other options. If this is the only thing that works, they keep coming.”

Scientists continue researching ketamine’s antidepressant effects on treatment-resistant depression. A recent clinical trial found that, in patients whose depression was not due to psychosis, ketamine was as effective for treatment-resistant depression as electroconvulsive therapy (ECT), which has long been the gold standard for hard-to-treat depression.The study found that 55% of those receiving ketamine and 41% of those receiving ECT had at least a 50% improvement in their self-reported depression symptoms.

A follow-up clinical trial is now underway comparing ketamine and ECT treatments among patients with suicidal depression. If ketamine can temper suicidal thoughts, it could be lifesaving.

Even though doctors and researchers are hopeful about the promise of ketamine, there is growing concern about the proliferation of private ketamine clinics, which began to crop up around the country after restrictions on telemedicine relaxed during the pandemic. These clinics offer IV ketamine infusions, with prices ranging from $600 to $800 per infusion, which raise the issue of affordability. Ketamine treatment for depression is not a “one shot and you’re done” matter; patients will need repeated treatment and many patients with depression cannot afford repeated treatments at this price.

Most ketamine private clinics operate in a gray zone, with almost no oversight, and function as for-profit businesses. Ketamine is not nearly as addictive as alcohol or opioids, but its use as a recreational drug poses serious risks.

At the MGH clinic, patients receive low doses of ketamine in long intervals and have mixed experiences. While some report feeling relaxed, others find it unpleasant, but most say their symptoms of depression improve and don’t interfere with day-to-day functioning.

Still, Dr Cusin warns that ketamine should not be a first-option treatment for depression. She pointed out that there are alternatives – perhaps as many as 80 different treatments to consider. She said, “It’s rare that somebody has tried everything. Usually, there are entire classes of medications or treatments that have not been considered. There is always hope.”

This is an exceptionally tricky topic for Doc Gumshoe to comment on. Depression can run the gamut from a fairly normal response to the circumstances of life to a psychological disorder. A person can feel depressed as a consequence of something like being terminated from a job or losing a close friend. But some individuals feel depressed when there is no specific factor that would rationally account for that feeling. A treatment option that works about 50% of the time in about 50% of the individuals who use it is certainly better than nothing. If we were discussing a potentially fatal disease, those one out of four odds of survival would sound pretty good. But when we’re talking about depression, I’m wondering if other forms of therapy might not work just as well, or even better – e.g., talking therapy, physical or intellectual activity, communication with a friend. The prospect of using a drug like ketamine to treat depression leaves Doc Gumshoe with serious doubts.

*****

The subjects that I addressed in this epistle are perhaps not the most positive and encouraging. I hope I have not cast a pall over the prospects for this new year. In the next Doc Gumshoe, I will take one more look at what’s going on in the Alzheimer’s disease front. A hint: there are some positive developments!

Many, many thanks for comments, and may this new year bring health and happiness!

Best to all, Michael Jorrin (aka Doc Gumshoe)