This is part 2 of this article. To get more context, read part 1 first.

Grape Pomace

Grape pomace is the remaining skin and seed byproduct leftover after grapes are pressed. This waste product is often thrown away or put back into the soil, or sometimes given to animals in their feed to improve their health, as it is a potent antioxidant.  Occasionally it is used for resale as a nutritional supplement.  It appears that few have explored its potential for use with migraine headache, although this company (Two Willows Farm) is selling grape seed and skins with or without pine bark (which has also been effective in alleviating migraines).

As it turns out, grape pomace also contains proanthocyandins, (the main constituent of Sangre de Grado), although it is unclear whether it is due to proanthocyandins that it affects CGRP levels. As mentioned in the section above on Sangre de Grado, proanthocyandins – specifically, those from grape seed – inhibit proinflammatory prostaglandin E associated with migraine.

Grape pomace is also high in the flavonoid quercetin, which is a known mast-cell stabilizer (and therefore reduces histamine levels). Brain mast cells can also secrete pro-inflammatory and vasodilatory molecules such as interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), selectively in response to corticotropin-releasing hormone (CRH), a mediator of stress which is known to precipitate or exacerbate migraines. (Source)

In Italy, researchers found melatonin or melatonin-like stubstances in different grape varieties.  Low melatonin levels are associated with migraine.  As it turns out, melatonin also inhibits CGRP levels (at least in rats).  (Low melatonin is also associated with adrenal insufficiency, so presumable, improved melatonin levels would help with kidney/adrenal health as well).

Concentration-dependent dilation of the rat middle cerebral artery produced by CGRP . . . was significantly inhibited in the presence of . . . melatonin. . . In addition, CGRP-mediated increase in adenylate cyclase activity was also significantly attenuated by the receptor mediated action of melatonin. These results indicate that melatonin may interact with CGRP to regulate cerebral arterial tone. (Source).

A study at George Mason University (Effect of Grape Pomace Extract on In Vitro CGRP Secretion as a Proxy for Migraine) concluded that “Results from the study provide evidence that chemicals in grape pomace extract reduce the levels of CGRP secreted.”  In other words, they don’t work as CGRP receptor antagonists, but rather prevent the secretion of CGRP in the first place. Another set of rats orally fed grape seed extract for 14 days had lower basal expression of CGRP in the neurons and microglia of the trigeminal nucleus caudalis than control rats.

In the study “Impact of Food Components on in vitro Calcitonin Gene-Related Peptide Secretion—A Potential Mechanism for Dietary Influence on Migraine”, impacts of grape pomace, ginger, and S-petasin (a compound found in butterbur) were studied on cell cultures.

Interestingly, grape pomace extracts displayed the strongest ability to inhibit CGRP secretion of any of the tested substances. This is notable not only for the scale of the inhibition, but also because the grape pomace extracts did not significantly inhibit calcium uptake upon stimulation. This suggests that inhibition of CGRP release of grape pomace extracts occurs by a mechanism different from calcium channel inhibition. . . Presumably, as red grapes, both pomace extracts would also contain anthocyanins, procyanidins, flavonols, and catechins. It is reasonable to propose these phenolic acids and polyphenolics may be responsible for the activity witnessed here.(Source)

As with many studies of plant compounds, the conclusions about the role grape pomace plays in CGRP levels were reached based off of analysis of results obtained from studies in cell cultures or animals, and not consumption by human beings.  But there have bee studies of grape pomace’s effects on other health markers in humans.  Grape pomace extracts and procyanidins have been associated with reduced risk of cardiovascular diseases such as atherosclerosis and shown to slow down degradation of skin collagen and elasticity associated with ageing.

Additional research has shown that in ruminants, grape pomace consumption increase sperm motility and improved faecal microflora in lambs.  Grape pomace also was shown to enrich soil phosphorus levels in soils supplemented with grape pomace biochar.  The dietary fiber and phenols in grape phenolic extract (1mg/mL) also induced a “significant biomass increase of L. acidophilus grown in liquid culture media“, which could theoretically translate into improved gut health and microflora when consumed by humans.

Currently, I am in the process of sourcing whole, dried, organic grape pomace in the Columbia Gorge region where I live to feature in my shop. The drying process does reduce the total phenolic content as compared to consumption of fresh grape pomace, but the end product still contains significant beneficial properties. My hope is to find a source in whole dried form that can then be powdered on the spot in a spice grinder for optimal freshness by the migraineur, preventing oxidation that would occur with pre-ground grape pomace powders.

Ginger & Butterbur

As the above cited study states, both ginger and butterbur (in the form of s-petasin) demonstrated “a mild decrease in calcium uptake as well as a mild reduction in CGRP secretion”, which may have been affected by the calcium channel blocking effects of these two plants.

While there may be other properties in both ginger and butterbur that help with migraine through other mechanisms, it appears that neither have such significant effects on lowering CGRP levels on their own as compared to either Sangre de Grado or grape pomace, which do not seem to be calcium channel blockers.  Perhaps a blend of these herbs and foods would have a more positive synergistic effect?

Other Plant Compounds that Affect CGRP Levels

Plants, as a rule, possess dynamic properties – with multiple molecules working together in synergistic (and unpredictable ways).  I wanted to share some notes I’ve taken about different plant compounds and how those compounds may affect CGRP, without concluding that all plants containing these compounds will necessarily help reduce migraines (as indicated by the fact that theobroma cacao lowers CGRP levels but is also a known migraine trigger.  It could be that the tyramine levels in cacao due to fermentation have a stronger physiological effect than the CGRP-inhibitory effect of the theobroma).  Notice that many compounds that inhibit CGRP also happen to reduce glutamate levels and are vasoconstrictive. CGRP and glutamate levels are both affected by calcium channel activation.

Compounds that Lower CGRP (Potentially Helpful in Alleviating Migraine)

  • Piperine – found in black pepper; also vasoconstrictive.
  • L-malate (ie, malic acid) – found in apples and many other tart fruits. It is a precursor to oxaloacetate, which reduces glutamate levels as well.
  • Ferulic acid – found in flax seeds, rice bran, and the Chinese herb Danshen (Salvia miltiorrhiza). Also reduces glutamate leves. Flax seeds also contain prebiotic gums.
  • Caffeic acid – in coffee, danshen and other plants such as celery.
  • Rosmarinic acid, an ester of caffeic acid – found in the herb Danshen and rosemary essential oil; also known to be a vasoconstrictor.
  • Interestingly, theobroma cacao from chocolate (a known migraine trigger) was also shown to decrease CGRP levels (in rats). Perhaps the tyramines overshadow the benefits of reduced cgrp!

Compounds that Raise CGRP (best avoided)

  • Capsaisin – present in chilli.
  • Cannabidiol – in cannabis; also a vasodilator. “the cannabidiol-evoked CGRP release depended on extracellular calcium.”

Stay Tuned for More Info . . .

Stay tuned for future blog posts in which we will explore the role that GABA, Serotonin, gut bacteria, melatonin, and electrolytes play in CGRP levels.

Please note that this information is for educational purposes only and is not intended to diagnose or treat migraines, or act as a replacement for medical care from a medical professional.

Empower Yourself to Heal from Chronic Migraine

The SimplyWell Protocol is available in our shop along with other e-books and products related to nutritional healing of migraine.

Or go to our services page to book a one-on-one coaching session or hair tissue mineral analysis with Marya Gendron (includes a copy of the SimplyWell Protocol and other e-books).

Marya Gendron

Marya Gendron is a biodynamic craniosacral therapist and health coach specializing in chronic migraine headache relief and alleviation of brain fog, indigestion, and histamine intolerance through plant-based solutions and hair mineral analysis. She practices out of White Salmon, Washington.