Angiogenesis and Why It Matters

In the beginning – there was angiogenesis – the creation of blood vessels. Tumors use it to keep growing. And, as it turns out – our fatty tissue also needs it to expand. So, might an anti-angiogenic approach work for weight loss, too?

Many of our modern front-line therapies against cancer incorporate “anti-angiogenesis” strategies, from the Greek words angio-, meaning vessel and genesis, meaning creation. So, anti-angiogenesis is opposing the creation of blood vessels. In other words, fighting cancer by cutting off tumor supply lines.

Some cancers are only able to grow to about the size of the tip of a ballpoint pen without a blood supply. Tumor growth then stalls. Autopsy studies show that virtually everyone has these tiny tumors in them by age 70. Cancer-without-disease can, therefore, be considered the normal state during aging.

To commandeer a blood supply, tumors diabolically release angiogenic factors, chemicals that cause new blood vessels to sprout toward the cancer. Once a blood vessel reaches the tumor and attaches, it’s off to the races—the tumor can then take off exponentially. By starving cancer of its blood supply, chemotherapy that blocks this process can sometimes cause tumors to shrink. But ideally, we wouldn’t have to wait until such a late stage to nip them in the bud. That’s where our diet can come in. Many of the phytonutrients we know and love in tea, spices, berries, broccoli, and beans have anti-angiogenic properties. Given the power of plants, the foundation of an anti-angiogenic approach to cancer has been considered a whole food plant-based diet.

But, the title of this video is, “Targeting angiogenesis to lose weight.” What does this have to do with obesity? Well, think about it. Tumors aren’t the only tissue in the body with expanding volume. The average tumor picked up by mammograms is only about the size of a marble, and it can take breast cancer decades to grow. Whereas, overfeed people and you can easily add an entire pound of fatty tissue in a matter of days. And, body fat is highly vascularized. Each fat cell in our body is essentially surrounded by tiny blood vessels. In large liposuction operations, a third of what’s vacuumed out is straight blood.

Throughout adulthood, our fatty tissue is constantly remodeling, expanding, and shrinking based on our day-to-day energy demands. This requires the development and retreat of extensive networks of new blood vessels. The human body already contains 60,000 miles of blood vessels. Imagine how many more miles have to be constructed when we gain weight. Without angiogenesis, without the sprouting of all these new blood vessels, we wouldn’t be able to add all that fat. Now, do you see where this is all going?

To expand, fat cells release the same kind of chemicals that tumors do to swell its blood supply. Fatty tissue is so angiogenic, open-heart surgeons have even tried grafting fatty tissue directly onto the heart after a heart attack, in hopes it would foster the growth of arteries to bypass the blockages. You can take fat samples from obese individuals during bariatric surgery, place them on living membranes of a fertile chicken eggs, and within a week, the fat is literally engulfed in blood vessels. That may even help explain why excess body fat can accelerate cancer growth.

Obesity increases the risk of more than a dozen different cancers, increasing the overall risk of getting and then dying from cancer by about 20 percent. All those angiogenic factors released from our increasing body fat may spill out into our bloodstream, resulting in higher blood levels among overweight individuals, which can then drop back down when we lose weight. So, maybe we could get the best of both worlds if we treated obesity like a tumor, using anti-angiogenic strategies to prevent the expansion of our fat mass in the first place. There are anti-angiogenic drugs, as well as anti-angiogenic foods. We’ll explore both, next. 

Body fat is probably the most highly vascularized tissue in the body—meaning has the most blood vessels. In fact, each individual fat cell is surrounded by an extensive network of tiny blood vessels. And, since the formation of these blood vessels appears to play a critical role in fatty tissue growth and reduction, the regulation of angiogenesis––the blood vessel formation process––may contribute to weight gain and weight loss. So, researchers tried injecting anti-angiogenic drugs into overfed lab animals and were able to induce profound weight loss in mice as well as in “nonhuman primates” (which is how scientists often refer to monkeys). The problem is that anti-angiogenic drugs can cause a variety of rare but fatal side effects. We may be willing to accept those risks in the context of cancer treatment, but when it comes to cancer prevention or obesity, anti-angiogenic diets would seem a safer bet (not to mention cheaper—anti-angiogenic drugs can cost $6,000 per dose). So, which foods are the most anti-angiogenic?

It’s interesting how they figured out that dietary components could be anti-angiogenic at all. Realizing that those eating plant-based diets were protected from diseases of excess angiogenesis, like cancer and diabetic vision loss, researchers took a group of plant-based eaters and starting pitting various components of their urine against the growth of human blood vessel cells harvested from discarded umbilical cords. The concentration of phytonutrients in the urine of vegetarians can be 30 times higher than that of the general population. Using this method, they identified a number of natural anti-angiogenic compounds in our diet. The question then became: could the levels required to block angiogenesis in a petri dish be reached in the bloodstream after eating a meal? The answer, researchers soon realized, is yes.

Anti-angiogenic concentrations of broccoli compounds can be reached in the bloodstream within an hour, eating less than three quarters of a cup of broccoli soup. So, these are totally doable kinds of quantities. You’ll note most of these compounds may cleared from our body within six hours, though, and fall back to nearly zero within 24 hours. So, we should strive to eat cruciferous vegetables at least once a day. Anti-angiogenic concentrations of b-cryptoxanthin can be reached within hours of eating two cups of red-fleshed papaya. One and a quarter cup of boiled onions may get you an anti-angiogenic dose of quercetin circulating in your blood in less than an hour. The level of protective soybean compounds that may be necessary has been found in the bloodstream of those eating ordinary Japanese diets. Now, I’m not dreaming up some sort of broccoli-papaya-onion-tofu casserole; these are just examples showing anti-angiogenic concentrations can be achieved within your bloodstream after eating reasonable serving sizes.

In general, the most concentrated dietary sources of polyphenols, the class of phytonutrients containing many of the anti-angiogenic compounds discovered to date, are herbs and spices. The only others to place in the top ten (out of more than 450 foods tested) were berries, cocoa powder, and ground flaxseeds. On a per-serving basis, most of the top contenders are berries, with artichokes leading the vegetables and whole grain rye leading the grains. Ironically, yogurt is a leading source in the United States, but only because most are fruit-flavored, with many containing berries as ingredients, whereas even plain soy yogurt makes it into the top 25.

For cancer prevention, researchers suggest the “constant consumption” of anti-angiogenic foods. Do we have evidence that it’s having an effect? Well, based on the analysis of more than a thousand tumors from one of Harvard’s studies of male health professionals, men eating the most tomato products had significantly less angiogenesis within their tumor, which then appeared to translate into a reduced risk of fatal disease. Yeah, but would the same anti-angiogenic potential of fruits and vegetables also help keep our bellies from growing? There’s only one way to find out!

A meta-analysis of more than a dozen randomized controlled trials of fruits and vegetable interventions for overweight individuals found six extra pounds of weight loss. But, that could be from a whole variety of factors, like decreased calorie density from the fiber and water content. But, maybe angiogenesis inhibition is playing a role?