Mother Nature creates delicious fruits full of ingredients that can help give us long lives free from disease and many of the infirmities of aging. But then, in a perverse act of peevishness, she makes these ingredients largely unavailable to us.
I'm talking about the class of chemicals known as polyphenols. Many have a multitude of tantalizing biological effects but, unfortunately, they just aren't absorbed that well. Many just pass largely unaltered through the digestive system and into the sewage system.
Blueberries in particular contain a particularly powerful (and elusive) branch of polyphenols known as anthocyanins. Harnessing their power could convey an impressive list of beneficial effects, from limiting abdominal obesity to mimicking the life-extending capabilities of calorie restriction diets.
Getting at these anthocyanins, though, is hard, unless you ingest them with the milk-protein casein.
You know casein, right? It's generally thought to be the best muscle-building protein and it's the basis of the best protein powders. If, however, you were to examine a high-quality casein through an electron microscope, you'd likely see peptides (short chains of amino acids) joined together in amorphous but stable agglomerates known as micelles.
From a muscle-building perspective, casein that's rich with micelles is particularly desirable because micellar casein is the only protein that's been definitively shown in lab studies to actually be anti-catabolic (Boire, 1997). That means that not only does it increase protein synthesis, it helps prevent muscle breakdown during and after intense exercise.
But there's something else particularly unusual and beneficial about these micelle agglomerates – their internal structure is porous. Look inside them and you see channels a tad bigger than 5 nanometers. Look further and you see inner cavities ranging in size from 20 to 30 nanometers.
It's these channels and cavities that are of particular interest to us when it comes to blueberry anthocyanins (and probably other polyphenols from a variety of sources).
The channels and cavities actually provide "shelter" and "safe passage" to anthocyanins and their metabolites, allowing them to bypass the stomach lining and enter the bloodstream where they can work their magic to make you healthier.
This isn't just theory, either. Scientists recently combined blueberries with casein and, after feeding the mixture to rats, found that absorption of anthocyanins and their metabolites increased anywhere from 1.5 to 10.1 times, depending on the specific anthocyanin or metabolite.
And maybe you think this phenomenon is limited to rats, but there's absolutely no reason to think it doesn't work with humans, too.
We all know, through momma's advice and rote learning, that blueberries are "good for us," but it's sometimes worth the effort to dig into exactly what they can do.
Their superpowers come from a number of anthocyanins and metabolites (cyanidin-3-glucoside, ferulic acid, vanillic acid, gallic acid, delphinidin-3-glucoside, etc.), but probably the one that's of most interest to humans is cyanidin-3-glucoside, or C3G.
This particular anthocyanin, responsible for much of the blueberry's color, has been found to have the following effects on mammalian physiology:
- C3G enhances the uptake of glucose by myotubes, causing calories to be preferentially used by muscle fibers instead of being stored as fat.
- C3G raises levels of adipokinectin, which regulates glucose levels and increases fatty acid breakdown.
- C3G decreases levels of leptin, a hormone directly connected to body fat and obesity.
- C3G improves endurance by increasing the production of chemical intermediates involved in the production of ATP, the cell's energy currency.
- C3G increases insulin sensitivity.
- C3G limits weight gain.
- C3G, taken before a workout, helps shuttle energy from pre-workout nutrition directly to muscle cells.
- C3G enhances the activity of brown adipose tissue.
- C3G induces the transformation of white adipose tissue to brown adipose tissue.
- C3G increases mitochondrial number and function.
- C3G prevents mitochondrial dysfunction.
- C3G limits abdominal obesity.
- C3G reduces systemic inflammation.
- C3G reduces triglycerides.
- C3G lowers blood sugar.
- C3G reduces cholesterol.
- C3G reduces chances of developing cancer.
- C3G improves survival rates of cancer.
- C3G improves skeletal muscle endurance by increasing levels of ATP.
- C3G improves night vision and helps prevent eye fatigue.
- C3G promotes liver health and fortifies it against damage from alcohol.
- C3G reduces risk of heart attack.
- C3G mimics the life-extending benefits seen in calorie restriction diets.
- C3G reduces inflammation in fat cells, causing them to shrink.
- C3G compares favorably in laboratory experiments with acarbose, a prescription glucose-disposal drug.
You clearly want to get C3G and other blueberry anthocyanins and metabolites into your system, but just eating a handful of naked blueberries isn't the best way to do it. You want to combine your blueberries with a casein-based protein drink, as in a blended protein drink.
However, there's another alternative that works even better.
Biotest faced the anthocyanin-absorption problem several years ago when it wanted to bring its Indigo-3G® product to market. Its solution was to combine cyanidin-3-glucoside with a pharmaceutical standby called gelucire.
Gelucire is a mixture of mono, di, and triglycerides that's used to increase the bioavailability of various drugs. In other words, it's a blend of fatty acids that have extreme hydrophobicity and low density, making it an ideal compound/drug carrier.
So Biotest took pure cyanidin-3-glucoside, each batch chemically harvested from an impressive amount of blueberries, and combined it with gelucire to make an extremely potent anthocyanin delivery system. The exact calculations are beyond me right now, but you'd have to have a gastronomically contraindicated number of blueberry/casein shakes to approximate the dosage and effects of one serving of Indigo-3G.
However, IF you've got some blueberries handy and you're preparing a protein (casein-based) drink, blend them together to thwart nature's mischievous intent and get the most out of those blueberries.
- Lang Y et al. Effects of Alpha-Casein on the Absorption of Blueberry Anthocyanins and Metabolites in Rat Plasma Based on Pharmacokinetic Analysis. J Agric Food Chem. 2021 Jun 9;69(22):6200-6213. PubMed.
- You Y et al. Cyanidin 3-glucoside attenuates high-fat and high-fructose diet-induced obesity by promoting the thermogenic capacity of brown adipose tissue. Journal of Functional Foods. 2018 Feb;41:62-71.
- Shi M et al. The effect of cyanidin-3-O-β-glucoside and peptides extracted from yoghurt on glucose uptake and gene expression in human primary skeletal muscle myotubes from obese and obese diabetic participants. Journal of Functional Food. 2018 Dec;51:55-64.
- Guo H et al. Cyanidin-3-O-β-glucoside regulates fatty acid metabolism via an AMP-activated protein kinase-dependent signaling pathway in human HepG2 cells. Lipids Health Dis. 2012 Jan 13;11:10. PubMed.
- Wei X et al. Cyanidin-3-O-β-glucoside improves obesity and triglyceride metabolism in KK-Ay mice by regulating lipoprotein lipase activity. J Sci Food Agric. 2011 Apr;91(6):1006-13. PubMed.
- Guo H et al. Cyanidin 3-glucoside attenuates obesity-associated insulin resistance and hepatic steatosis in high-fat diet-fed and db/db mice via the transcription factor FoxO1. J Nutr Biochem. 2012 Apr;23(4):349-60. PubMed.
- Sasaki R et al. Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice. Biochem Pharmacol. 2007 Dec 3;74(11):1619-27. PubMed.
- Tsuda T et al. Anthocyanin enhances adipocytokine secretion and adipocyte-specific gene expression in isolated rat adipocytes. Biochem Biophys Res Commun. 2004 Mar 26;316(1):149-57. PubMed.
- Guo H et al. Cyanidin 3-glucoside protects 3T3-L1 adipocytes against H2O2- or TNF-alpha-induced insulin resistance by inhibiting c-Jun NH2-terminal kinase activation.Biochem Pharmacol. 2008 Mar 15;75(6):1393-401. PubMed.
- Tsuda T et al. Microarray profiling of gene expression in human adipocytes in response to anthocyanins. Biochem Pharmacol. 2006 Apr 14;71(8):1184-97. PubMed.
- Tsuda T et al. Gene expression profile of isolated rat adipocytes treated with anthocyanins. Biochim Biophys Acta. 2005 Apr 15;1733(2-3):137-47. PubMed.
- Grace MH et al. Hypoglycemic activity of a novel anthocyanin-rich formulation from lowbush blueberry, Vaccinium angustifolium Aiton. Phytomedicine. 2009 May;16(5):406-15. PubMed.
- Tsuda T et al. Dietary cyanidin 3-O-beta-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. J Nutr. 2003 Jul;133(7):2125-30. PubMed.