Summary: the most extensive study to date reveals a modest but significant increase in breast cancer risk from alcohol consumption that should be balanced against the risk for cardiovascular disease.

An important study just published in JAMA (the Journal of the American Medical Association) goes further than all previous studies in examining the association between modest alcohol consumption over extended periods of time and breast cancer. The authors state:

“Multiple studies have linked alcohol consumption to breast cancer risk, but the risk of lower levels of consumption has not been well quantified. In addition, the role of drinking patterns (ie, frequency of drinking and “binge” drinking) and consumption at different times of adult life are not well understood.”

This new study is important because it followed women over a longer period of time and included for factors that can also alter breast cancer risk such as pregnancy, ionizing radiation, etc. in 105,986 nurses over 28 years as the authors set out to…

“…evaluate the association of breast cancer with alcohol consumption during adult life, including quantity, frequency, and age at consumption.”

Their data show that the amount of alcohol rather than frequency of drinking is associated with breast cancer risk, and that age doesn’t matter:

“During 2.4 million person-years of follow-up, 7690 cases of invasive breast cancer were diagnosed. Increasing alcohol consumption was associated with increased breast cancer risk that was statistically significant at levels as low as 5.0 to 9.9 g per day, equivalent to 3 to 6 drinks per week. Binge drinking, but not frequency of drinking, was associated with breast cancer risk after controlling for cumulative alcohol intake. Alcohol intake both earlier and later in adult life was independently associated with risk.”

Analysis of their data also revealed a trend for a 10% increase in breast cancer risk for each 10 gram increase in alcohol consumption. The mechanism is not certain, but because the greatest impact was on hormone receptor-positive breast cancer it is likely related to the tendency for alcohol to increase circulating levels of estrogen. The authors conclude:

“Low levels of alcohol consumption were associated with a small increase in breast cancer risk, with the most consistent measure being cumulative alcohol intake throughout adult life. Alcohol intake both earlier and later in adult life was independently associated with risk.”

As with everything else in medicine, the information needs to be considered in the context of each woman’s individual health and family history, including the balance of risks for cancer and heart disease.

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A study just published in PloS Medicine (Public Library of Science) offers more evidence that alcohol consumed in moderation can promote overall health and successful aging for women. The data presented also helps to firm up guidelines for determining amounts that are beneficial and harmful. The authors state:

“Observational studies have documented inverse associations between moderate alcohol consumption and risk of premature death. It is largely unknown whether moderate alcohol intake is also associated with overall health and well-being among populations who have survived to older age. In this study, we prospectively examined alcohol use assessed at midlife in relation to successful ageing in a cohort of US women.”

They defined “successful ageing” as being free of 11 major chronic diseases and having no major cognitive impairment, physical impairment, or mental health limitations, and applied this to the 13,894 Nurses’ Health Study participants who survived to age 70 or older for whom they had comprehensive and continuously updated health data. This was correlated with habits of alcohol consumption. Their data paints an interesting picture:

“…light-to-moderate alcohol consumption at midlife was associated with modestly increased odds of successful ageing. The odds ratios were 1.0 (referent) for nondrinkers, 1.11 for ≤5.0 g/d, 1.19 for 5.1–15.0 g/d, 1.28 for 15.1–30.0 g/d, and 1.24 for 30.1–45.0 g/d. Meanwhile, independent of total alcohol intake, participants who drank alcohol at regular patterns throughout the week, rather than on a single occasion, had somewhat better odds of successful ageing; for example, the odds ratios were 1.29 and 1.47 for those drinking 3–4 days and 5–7 days per week in comparison with nondrinkers, respectively, whereas the odds ratio was 1.10 for those drinking only 1–2 days per week.”

In other words, consuming 30 to 45 grams of alcohol per day conferred a 24% increase in the odds for successful aging. Moreover, drinking 5-7 days per week increased the odds of a good outcome by 47%. The authors conclude:

“These data suggest that regular, moderate consumption of alcohol at midlife may be related to a modest increase in overall health status among women who survive to older ages.”

So how much is 30 to 45 grams of alcohol? A ‘standard drink‘ = 10 grams of pure alcohol. A 750 ml (regular size) bottle of red wine with a typical 14% alcohol volume equals approximately 8.3 standard drinks (82.8 grams of pure alcohol). A 30 ml (one ounce) shot of 80 proof (40% alcohol volume) is 9.4 grams of pure alcohol (just shy of one standard drink). An ounce of stronger spirits like 94 proof gin or vodka is 11.12 grams of pure alcohol.

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More data on the effect of alcohol on health is offered by a study recently published in the journal Acta Neurologica Scandinavica in which the authors specifically investigate its influence on the risk of dementia.

“The impact of moderate alcohol consumption on cognitive function and dementia is unclear. We examined the relationship between consumption of different alcoholic beverages and cognitive function in a large population-based study.”

Their study subjects were 5033 Norwegian men and women whose alcohol consumption was correlated with cardiovascular risk factors and cognitive function at baseline and after 7 years. What did the data show?

“Moderate wine consumption was independently associated with better performance on all cognitive tests in both men and women.“

Moreover…

“There was no consistent association between consumption of beer and spirits and cognitive test results. Alcohol abstention was associated with lower cognitive performance in women[!].“

There are a lot of good reasons to not drink alcohol; but for those whom it is not contraindicated, their conclusion is interesting:

“Light-to-moderate wine consumption was associated with better performance on cognitive tests after 7 years follow up.”

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Alcohol in excess is a significant promoter of accelerated neurodegeneration. The authors of a welcome paper recently published in Free Radical Biology and Medicine first elucidate the…

“…cellular and biochemical mechanisms of alcohol-induced oxidative damage in different types of brain cells.”

Interestingly, alcohol administration generated increased levels of reactive oxygen species (‘free radicals’) localized mainly in the astrocytes and microglia (‘housekeeper’ immune cells in the brain). As a result,

“Oxidative damage in glial cells was accompanied by their pronounced activation (astrogliosis) and coincident neuronal loss, suggesting that inflammation in glial cells caused neuronal degeneration.“

In other words, the oxidative stress induced by alcohol resulted in an autoimmune inflammatory attack on brain tissue. But here’s the good news:

“Co-administration of ALC [acetyl-L-carnitine] with alcohol showed a significant reduction in oxidative damage, neuronal loss and a restoration of synaptic neurotransmission in this brain region, suggesting that ALC protects brain cells from ethanol-induced oxidative injury. These findings suggest the potential clinical utility of ALC as a neuroprotective agent that prevents alcohol-induced brain damage and development of neurological disorders.”

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Landmark research just published in PLoS Genetics (Public Library of Science) brings to light two important points in breast cancer diagnosis and treatment. First, the authors prove that defects in methylation (addition of a methyl group) a critical process for maintaining DNA health, is a powerful prognostic indicator for breast cancer outcome. The authors first observe:

“Although tumor size and lymph node involvement are the current cornerstones of breast cancer prognosis, they have not been extensively explored in relation to tumor methylation attributes in conjunction with other tumor and patient dietary and hormonal characteristics…We investigated DNA methylation profiles in over 160 well annotated breast tumor samples and found significant relationships with standard and other known predictors of prognosis, as well as established risk factors for disease: alcohol intake and dietary folate.”

They measured the methylation patterns of critical genes primary breast tumors from 162 women. Their findings are compelling:

“Tumor grade, size, estrogen and progesterone receptor status, and triple negative status were significantly associated with altered methylation…”

The second valuable point confirms the role of alcohol intake and folate status, both known to impact methylation capability.

“Using multinomial logistic regression to adjust for potential confounders, patient age and tumor size, as well as known disease risk factors of alcohol intake and total dietary folate, were all significantly associated with methylation class membership.”

The authors’ conclusion indicates the profound importance of assessing and protecting methylation capacity:

“Breast cancer prognostic characteristics and risk-related exposures [alcohol and folate status] appear to be associated with gene-specific tumor methylation, as well as overall methylation patterns.”

I use measurements of urinary methylmalonate and formiminoglutamate, objective indicators of important methylation cofactors. One or both of these is typically abnormal in patients with breast cancer. In my opinion, measuring this and treating methylation abnormalities with physiological interventions should be part of the standard of care for breast cancer.

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Adding more concern to the reported increase in heavy alcohol consumption among adolescents is the emerging science regarding alcohol’s effect on the brain. This research just published in the Proceedings of the National Academy of Sciences elucidates the mechanism by which binge drinking damages the developing brain.

“Binge alcohol consumption in adolescents is increasing, and studies in animal models show that adolescence is a period of high vulnerability to brain insults. The purpose of the present study was to determine the deleterious effects of binge alcohol on hippocampal neurogenesis…”

The authors made a number of startling observations regarding the effect of alcohol on the brain’s center for short-term memory and adrenal regulation, the hippocampus:

“Heavy binge alcohol consumption over 11 mo dramatically and persistently decreased hippocampal proliferation and neurogenesis…Alcohol significantly decreased the number of actively dividing type 1, 2a, and 2b cell types…suggesting that alcohol interferes with the division and migration of hippocampal preneuronal progenitors. Furthermore, the lasting alcohol-induced reduction in hippocampal neurogenesis paralleled an increase in neural degeneration mediated by nonapoptotic pathways.”

Yikes. The authors sum up their findings with these memorable comments:

“Altogether, these results demonstrate that the hippocampal neurogenic niche during adolescence is highly vulnerable to alcohol… This lasting effect, observed 2 mo after alcohol discontinuation, may underlie the deficits in hippocampus-associated cognitive tasks that are observed in alcoholics.”

A fascinating paper published last month in the Journal of Neuroscience now reveals how alcohol feeds an immune inflammatory attack on the brain:

“Toll-like receptors play an important role in the innate immune response, although emerging evidence indicates their role in brain injury and neurodegeneration. Alcohol abuse induces brain damage and can sometimes lead to neurodegeneration. We recently found that ethanol can promote TLR4 signaling in glial cells by triggering the induction of inflammatory mediators and causing cell death, suggesting that the TLR4 response could be an important mechanism of ethanol-induced neuroinflammation.”

This is an extremely persuasive argument for moderation for anyone interesting in preserving brain health.

The authors go on to report that TLR4 is critical for ethanol-induced inflammatory signaling in glial cells by demonstrating that ‘turning off’ TLR4 prevents the neuroinflammatory brain damage:

“Our results demonstrate, for the first time, that whereas chronic ethanol intake upregulates…cytokine levels [interleukin (IL)-1β, tumor necrosis factor-{alpha}, IL-6] in the cerebral cortex,…TLR4 deficiency protects against ethanol-induced glial activation, induction of inflammatory mediators, and apoptosis. Our findings support the critical role of the TLR4 response in the neuroinflammation, brain injury, and possibly in the neurodegeneration induced by chronic ethanol intake.”

For us the main message is that excessive alcohol consumption fires up the brain’s glial cells (immune cells) and the resultant neuroinflammation does serious damage to the brain. This important research was highlighted in an editorial published last week in Science Translational Medicine which contains some notable comments:

“Ethanol is the most widely used psychotropic substance in the world, and chronic ethanol abuse leads to harmful changes in virtually every organ system in the body. Notably, this includes the brain, where consumption of alcohol can lead to irreversible changes in cognition, mood, and behavior. Although it has been known that this often involves degenerative, inflammatory-mediated processes, their precise nature has not been characterized. In a recent article, Alfonso-Loeches and colleagues report that much of the ethanol-induced inflammation in the brain depends on signaling through Toll-like receptors (TLRs). These receptors participate in innate immunity responses to infection but are also implicated in reactions to injury and degeneration in the brain.”

The editorial concludes with the compelling comparison of the brain damage done by activation by alcohol of neuroinflammation through Toll-like receptors with other common neurodegenerative conditions:

“These results suggest that TLRs play a critical role in alcohol-related brain changes, just as they have been previously implicated in Alzheimer’s disease, ischemic brain injury, and HIV infection.”

Besides curtailing excess and enjoying alcohol only in moderation we may be able to use coffee as protective therapy. There is abundant evidence of the benefit of coffee for the liver, including this recent study published in the journal Inflammation Research. The authors present data that:

“Treatment with caffeine significantly attenuated the elevated serum aminotransferase enzymes and reduced the severe extent of hepatic cell damage, steatosis and the immigration of inflammatory cells… Furthermore, caffeine decreased serum and tissue inflammatory cytokines levels, tissue lipid peroxidation and inhibited the necrosis of hepatocytes. Kupffer cells isolated from ethanol-fed mice produced high amounts of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α), whereas Kupffer cells from caffeine treatment mice produced less ROS and TNF-α.”

The authors conclude:

“These findings suggest that caffeine may represent a novel, protective strategy against alcoholic liver injury by attenuating oxidative stress and inflammatory response.”

Could this protective effect extend to the brain? There’s a lot of emerging evidence that suggests the answer is ‘yes’. Fascinating research published last month in the journal Experimental Neurology demonstrates that caffeine protects the brain from the kind of damage involved in Parkinson’s disease caused by pesticides:

“Environmental exposures suspected of contributing to the pathophysiology of Parkinson’s disease (PD) include potentially neurotoxic pesticides, which have been linked to an increased risk of PD. Conversely, possible protective factors such as…caffeine have been linked to a reduced risk of the disease. Here we assessed whether caffeine alters dopaminergic neuron loss induced by exposure to environmentally relevant pesticides (paraquat and maneb) over 8 weeks.”

The data led to a conclusion that increases my enthusiasm for exercising the French press:

“Caffeine at 20 mg/kg significantly reduced TH+ neuron loss (to 85% of the respective control). The results demonstrate the neuroprotective potential of caffeine in a chronic pesticide exposure model of model of PD.”

As for Alzheimer’s disease, a supplemental issue of the Journal of Alzheimer’s Disease has no less than 22 papers on the benefits of caffeine for AD and other neurodegenerative disorders. I suggest you have a look, drink alcohol in moderation (or not at all if you prefer), and enjoy your coffee and tea if there are no contraindications.

With alcohol, as with so many other substances and stimuli, we can appreciate the principle of hormesis: a small amount may have benefit while a larger amount is harmful.

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A study just published in the Archives of Internal Medicine evaluated 19,220 US women aged 38.9 years or older over a period of almost 13 years to determine the effect of light alcohol consumption (1-2 drinks per day) on weight gain over the study period. Although it appears that they expected to obtain a different result, here is their conclusion:

“Compared with nondrinkers, initially normal-weight women who consumed a light to moderate amount of alcohol gained less weight and had a lower risk of becoming overweight and/or obese during 12.9 years of follow-up.”

Two caveats: heavier drinking blows the program and backfires. Some people should not drink at all.

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Don’t let this research go to your head, but an interesting study was just published in Heart, the journal of the British Cardiovascular Society. The investigators followed 15,630 men and 25,808 women for 10 years and found that moderate, high and very high alcohol consumption (1 to 6 standard drinks per day) was associated with 30% less CHD (coronary heart disease). The authors conclude: “In men aged 29-69 years, alcohol intake was associated with a more than 30% lower CHD incidence.” Sorry ladies, the data did not show a similar benefit for you. Gentlemen, before rushing to the liquor cabinet bear in mind that there are also important reasons for individuals to limit or abstain from alcohol (such as high insulin levels, etc). This is what the data in this study shows, but discuss it with your functional medicine doc.

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