Does a vitamin a day keep Alzheimer's at bay?

As regular readers of these posts know, I am generally not a big fan of using vitamins and supplements for healthy people who eat a reasonable diet. There is little solid data that these improve your health. A recent study has caused me to reconsider.

We all lose some memory function with aging, even those of us who will never develop dementia. Annoying “senior moments,” such as forgetting where we put the car keys or who wrote our favorite book, become increasingly common. What helps? Aerobic exercise has some benefit, while crossword puzzles, sudoku, etc. do not seem to do much. How about a pill?

A group of investigators from New York and Boston recently published the results of a trial studying the effects of a daily multivitamin (Centrum Silver) on memory in older adults. The trial was designed to test the effects of cocoa extract and multivitamins on cancer risk and cardiovascular outcomes but they used the trial to test other outcomes as well. It was a large trial: 12,666 women 65 or older and 8776 men 60 or older were enrolled.

The memory study used an internet-based battery of neuropsychological tests at baseline and repeated annually for 3 years. Importantly, the study used a memory test designed for healthy people.

You may recall the ridicule faced by Donald Trump in the summer of 2020 when he claimed to “have aced” a “really difficult test” that proved how smart he was. That test was the mini-mental status test (or something very similar), specifically designed to screen for dementia. Its weakness in studying healthy people is that it is so easy that most get high scores and subtle changes are hard to detect.

This study used a test called the ModRey test that is much harder and was designed to study memory changes in people without major memory impairment.

At both 1 and 3 years after they enrolled, people who were randomly assigned to take the multivitamin had significantly better memory scores than those assigned to placebo. The researchers estimated that the multivitamin improved memory performance over placebo by the equivalent of 3 years.

Since the treatment, an over-the-counter multivitamin, is harmless and cheap, it seems prudent to consider adding this to your daily routine. I plan to do so (when I remember).



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Menopause: Hot flashes or heart attack?

A new medication has just been approved by the FDA for the treatment of moderate to severe menopausal hot flashes, and I predict a barrage of television and other media advertising. In yesterday’s New York Times was an article headlined: A Movement to Make Workplaces ‘Menopause Friendly.’ Clearly a topic to be addressed.

Like most woman-specific health issues, menopause has been under-studied for years. For most of human history, women who lived long enough to pass through menopause were the lucky minority. As lifespans increased, menopause became “normal” and little but folklore was used to treat symptoms.

Menopause refers to the time a year after a woman has her last period. Perimenopause describes the years preceding, when menstrual periods may become erratic and many women begin to experience hot flashes. Each woman’s experience is different. I have had patients who will respond “I have not had a period in 6 months but feel fine,” while others have to bring a change of clothes to work. The cause of the ”vasomotor symptoms,” changes in the body's thermoregulatory system, leading to sudden feelings of heat, sweating, and skin flushing is clear: fall in estrogen. Hot flashes can occur after surgical removal of the ovaries or by medications that block estrogen, though natural perimenopause/menopause is the usual culprit.

Given the cause, the obvious treatment is estrogen, given by pill or skin patch. During the 1960’s, estrogen was widely prescribed as a panacea for all the issues of aging in women. But, a landmark study by the Woman’s Health Initiative (WHI) published in JAMA in 2002 claimed that giving hormone therapy to post-menopausal women led to more rather than fewer heart attacks and strokes, as well as increasing breast cancer risk. Prescriptions for estrogen plummeted.

At the time, I counselled my patients that the study was so flawed that it was irrelevant to them, but media coverage convinced most women that estrogen was akin to arsenic.

Why was it flawed? The study investigators set out to prove or disprove that HRT (hormone replacement therapy) prevented heart attacks. They enrolled a large number of women – over 16,600 – but were concerned there might not be enough heart attacks to result in the holy grail of “statistical significance” if they used only peri-menopausal younger women. The study group included women who were post-menopausal and 50-79 years old.

We know that menstruating women have many fewer heart attacks than men and that this protection is lost after menopause. By enrolling women who were many years or decades post-menopausal, they selected a group that were beginning to catch up to men in developing artery plaques and then exposing them to the known clot-promoting effects of estrogen. It should have been predicted that this group would have more heart attacks and strokes. How is HRT usually prescribed? It is given to women in their perimenopausal years, when they are still much less likely to have artery plaques. Much later re-analysis of the WHI data did show that the younger members of the study had fewer heart attacks when taking HRT while the older women had more.

What non-hormonal drugs can a woman take for bothersome hot flashes? Until very recently, the only approved drug was paroxetine, an anti-depressant that has been shown to reduce the severity and frequency of hot flashes. The new drug, which will be marketed as Veozah, works on the vasomotor center of the brain, and was shown in a recent study to provide superior relief to placebo. A small number of women taking it had liver test abnormalities, but side effects were generally few. The major side effect will be on the pocketbook. The drug will be marketed at a cost of $550/month, and will need to be taken for several years.

My suggestion? If your symptoms are mild, you do not need to take anything, or try soy milk.

What if your symptoms are worse?

If you are in your late 40’s or 50’s, ask your doctor about HRT. It has a good safety profile in younger women and is treating the underlying problem. Patches are generally safer than pills. If you have a history of (or strong family history of) breast cancer, HRT is not for you. In that case, see how much relief you get from paroxetine, generic and cheap. If that does not work, hope your insurance covers Veozah at a reasonable co-pay.

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