Nutrition research in recent decades has moved with great interest towards investigating the health effects of non-nutritive compounds.
Such compounds are biologically active, but are not essential nutrients in the way vitamins and minerals would be required to sustain life.
As such, some researchers have proposed that non-nutritive bioactive compounds like (poly)phenols, are “lifespan essential”, i.e., for promoting good health over a lifetime.
Of these (poly)phenols, the flavonols in cacao have been some of the most promising for potential meaningful impacts on human health, sparking intense interest in cocoa flavanols benefits.
Characterising Flavonoids in the Diet
The major classes of bioactive food components in the human diet are known as (poly)phenols.
If you’re wondering, the ‘poly’ in parentheses denotes that some compounds may have more than one phenolic ring, a type of chemical structure.
Compounds known as flavonoids constitute the major human dietary source of polyphenols, with the primary food sources including vegetables, fruits and fruit juices, tea, red wine, coffee, and chocolate.
Within the classification of flavonoid is a diverse chemical subgroup of compounds, including anthocyanins, flavonols, flavones, isoflavones, flavan-3-ols, flavanones, anthocyanidins and proanthocyanidins.
Flavonoids are responsible for the pigmentation of fruits and vegetables, in particular purples, blues, and reds [albeit not beets, because in fact, beets are given their colour from betanins].
The diverse chemical structures of the class of flavonoids and their metabolites are associated with a wide array of biological effects, which may influence health and disease processes.
Different foods possess different flavonoid compounds. For example, citrus fruits contain flavonols, while cocoa contains flavanols, and berries contain anthocyanins.
How do flavonoids exert beneficial effects on human health? A few mechanisms have been proposed, including:
- Interaction with brain pathways that induce the growth, survival, and repair of brain cells, and synaptic plasticity;
- Increased vascular blood flow, enhanced vascular function, and angiogenesis [the formation of new blood vessels];
- Protection from inflammation and other processes, e.g., excess nitric oxide production.
These mechanisms may reflect a truism in nutrition, that “what is good for the heart is good for the head”.
That is to say, generally, there is substantial overlap between the evidence for nutrients of benefit and concern for cardiovascular health and neurological health.
So, What of Cocoa Flavonols?
The Cocoa Supplement and Multivitamin Outcomes Study [COSMOS] was a randomised controlled trial investigating the effects of a cocoa extract supplement and/or a multivitamin supplement, aiming to definitively test cocoa flavanols benefits in a large-scale population.
Participants were 21,444 men and women over 60 years of age, who were randomised to one of four groups:
- Active cocoa and active multivitamin
- Active cocoa and placebo multivitamin
- Placebo cocoa and active multivitamin
- Placebo cocoa and placebo multivitamin
This type of design is known as a 2×2 factorial design, meaning that each treatment has two levels [in this case, both the cocoa and multivitamin have both placebo and active levels].
The dose of cocoa flavanols was 500mg and 80mg epicatechin per day, while the multivitamin was the U.S. commercial brand, Centrum Silver.
The primary outcome of the study was a composite of cardiovascular disease [CVD] events.
In addition, the COSMOS-Mind substudy of 2,262 participants from the parent trial who underwent cognitive assessments during the study analysed changes in global cognition scores as the primary outcome.
Outcomes for the Heart and Head
Over 3.6 years with 77,331 total person-years of follow-up, 570 participants died and 866 suffered a cardiovascular event.
In the cocoa supplement group, there was a 10% [HR 0.90, 95% CI 0.78 to 1.02] lower risk of total CVD events compared to the placebo group, which was not statistically significant, i.e., the 95% CI crossed 1.0.
However, for the secondary outcome of CVD mortality, there was a significant 27% [HR 0.73, 95% CI 0.54 to 0.98] lower risk of CVD death in the cocoa supplement group.
The cocoa supplement group also exhibited a significant 16% [HR, 0.84; 95% CI, 0.71, 0.99] lower risk of major CVD events [a tighter definition of CVD events confined to myocardial infarction, stroke, and CVD death].
Looking good so far for the heart with cocoa flavonols, but what about the head, raising questions about the extent of cognitive cocoa flavanols benefits?
In the cocoa group, there was no significant difference in global cognitive scores compared between active and placebo groups.
However, the multivitamin group showed a significant difference in the active group compared to the placebo group.
The cocoa supplement group also showed no differences in episodic memory or executive function, while there were significant effects of the multivitamin for both of these respective secondary outcomes.
Some Surprising Results: the Head
The findings of the COSMOS-Mind substudy surprised many in the field based on the lines of evidence in favour of cocoa flavonols prior to this trial, which heavily promoted neurological cocoa flavanols benefits.
However, the evidence from human intervention trials on cocoa flavonols up to the publication of COSMOS was primarily from acute studies of either 1 day or up to 8 weeks.
Nevertheless, this is also instructive because the COSMOS-Mind trial only conducted a single, annual cognitive assessment in participants.
Human cognition has both acute, short-term, and chronic, long-term domains. And studying these changes is notoriously difficult. If there are genuine acute effects, COSMOS-Mind would not have captured any such effects of cocoa flavonols.
Nevertheless, COSMOS-Mind is the largest and longest trial of cocoa flavanols to date.
Based on that fact alone, it is sufficient to raise an amber light over whether the previous research in small studies conducted either over 1-2 hrs, a single day or 8 weeks, is representative of the potential of cocoa flavanols to improve cognition in older adults.
Some Surprising Results: the Heart
The potential for (poly)phenol compounds to be beneficial for cardiovascular health goes all the way back to the Seven Countries Study.
In that study, flavonoids were independently associated with a lower risk of coronary heart disease over 25 years.
However, the trail somewhat went cold as the potential neurological benefits of flavonoids took centre stage.
Nevertheless, there is distinct biological plausibility of the findings of lower CVD risk.
Cocoa flavonols have been shown to significantly lower blood pressure, improve vascular function and protect the vascular endothelium, and improve blood cholesterol profiles.
While these effects have been shown in human intervention studies, they have mostly been short-term of < 4 weeks duration.
Nevertheless, the doses used in shorter-term trials were similar to the levels of cocoa flavanols and epicatechins used in the COSMOS trial.
Thus, there is congruence between the benefits of cocoa flavanols on cardiovascular risk factors observed in short-term interventions and the lower CVD risk found over the 3 years of the COSMOS study, solidifying the reality of cardiovascular cocoa flavanols benefits.
Note that, depending on the method of quantifying cocoa flavanol content, and the cocoa content of the type of, chocolate it could take 1kg of chocolate to obtain levels used in COSMOS.
However, benefits on blood pressure have been demonstrated with as little as 30mg cocoa flavanols, up to 240mg, levels which could easily be obtained with 20-40g ~80% cacao dark chocolate.
In addition, for generalisability, it is important to note the characteristics of the COSMOS sample; older, well-educated, and a degree of baseline risk reflected in the prevalence of hypertension and statin treatment.
For the cognitive outcomes, whatever further research may emerge for cocoa flavanols, arguably a much more ecologically valid finding with more immediate practical application is the effects of the multivitamin.
The findings certainly challenge the “multivitamins are expensive pee” meme, and while that may be the case in younger adults with adequate dietary intake, it could be a relatively inexpensive insurance policy in older adults to protect the brain.
Yours in Science,
Alan
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