Hemp Protein

Hemp is the common name for the plant Cannabis sativa, which has a history of being a multipurpose crop for fiber, food, and medicinal products; farming of Hemp was banned around 1930 due to the psychoactives in Marijuana and was repermitted in 1998 (Canadian data but appears to extend to Australia, Austria, China, Great Britain, France and Spain but not the US^[1]) due to Hemp being bred to contain less than 0.3% of the main main marijuana psychoactive (delta-9-tetrahydrocannabinol).^[2] All hemp products sold as food products (legally) abide by this and appear to contain less than 0.3% THC (in reference to total product weight).^[3][4]

Hemp can be cultivated for the oil component or the fiber component with the latter being more popular economically, and has some roots in Traditional Chinese Medicine where the seed kernel is referred to as Huo Ma Ren^[5] for the treatment of constipation, gastrointestinal disease, and aging.^[6] Hempseeds are also referred to as Fructus cannabis (fruits of cannabis).^[6]

The seeds of Hemp tend to contain Around 2200kJ (525kcal) per 100g 30.4+/-2.7% and 24.0+/-2.1% fatty acids and proteins respectively, with an ash (4.8+/-0.7%) and nondigestible fiber (22.2%) content. Other bioactives found somewhat exclusively in hempseeds include:^[7]

• Cannabidiolic acid^[8] and its parent molecule, Cannabidiol (both nonintoxicating)
• Cannabisin B^[9] at 66mg/g (6.6%) of a 60% methanolic extract^[5]
• N-trans-Caffeoyltyramine at 33mg/g (3.3%) of a 60% methanolic extract^[5]

With compounds not seen as unique to hemp including:

• Vitamin E (90mg/100g)^[7]
• Thiamin (0.4mg/100g)^[7]
• Riboflavin (0.1mg/100g)^[7]
• Phosphorus (1160mg/100g)^[7]
• Potassium (859mg/100g)^[7]
• Magnesium (483mg/100g)^[7]
• Calcium (145mg/100g)^[7]
• Iron (14mg/100g)^[7]
• Sodium (12mg/100g)^[7]
• Manganese and Zinc (7mg/100g)^[7]
• Copper (2mg/100g)^[7]

Much hemp oil can be extracted from the seeds via cold-processing and sold as its own nutritional supplement,^[7] the product after cold-processing is known as seed cake or seed meal and is approximately 10% fatty acids (oil) by weight with a comparably high protein content (30-50%).^[10][11][7]

When looking at the fatty acid composition overall, it appears to contain:

• Linoleic acid as omega-6 (56%)
• Alpha-linoleic acid as omega-3 (22%)
• Oleic acid (9%)
• Palmitic acid (5%)
• Gamma-linoleic acid (4%)
• Stearic acid (2%)
• Stearidonic acid (2%), an omega-3 fatty acid with the designation 18:4

The omega-6 and omega-3 ratio appears to be between 3:1 and 2:1,^[7] and Hemp is one of the few sources of Stearidonic acid (the other common source being blackcurrant oil).

Hemp seeds are fairly balanced in their macronutrient profile, and extraction of fatty acids to produce hemp oil leads a seed meal as byproduct; this seed meal is higher in protein (30-50%) and used as 'hemp protein'. The seeds are surprisingly low in sodium, and have a somewhat balanced omega fatty acid profile; like many plants, they may have a few unique polyphenolics or bioactives in them (these are cannabinoid compounds, although the psychoactive THC in Marijuana is not present in high amounts in commerical hemp anymore)

The composition of the seed meal appears to be:

• Around 1700kJ (406kcal) per 100g^[7]
• 40.7+/-8.8% protein content
• 10.2+/-2.2% fatty acid content
• 6.7+/-1% ash content
• 26.3% nondigestible fiber^[7]

When looking at the amino acid composition of the protein fragment, Hemp appears to contain:^[2][12]

• Threonine 2.66+/-0.67%
• Aspartate 1.35+/-0.23%
• Glutamine 1.73+/-0.32%
• Serine 6.03+/-1.24%
• Glycine 1.59+/-0.32%
• Proline 1.66+/-0.35%
• Alanine 1.61+/-0.32%
• Arginine 94−128 mg/g
• Cysteine 0.70+/-0.15%
• Valine 1.91+/-0.30%
• Methionine 0.88+/-0.25%
• Isoleucine 1.45+/-0.23%
• Leucine 2.35+/-0.45%
• Tyrosine 1.15+/-0.28%
• Phenylalanine 1.62+/-0.30%

When comparing the amino acid profile against other sources, Hemp is comparatively high in Arginine and Tyrosine (greater than all other common sources tested) and is high in Alanine and Aspartic acid alongside Soy (both being greater than other sources).^[7]

The protein of hemp appears to be incomplete as, although it contains all essential amino acids, some are in insufficient quantity to provide the bare minimum of essential human nutrition; The limiting amino acids in Hemp appear to usually be Lysine, with Leucine and L-Tryptophan being the second and third limiting amino acids.^[2] This makes it, from a complementary protein perspective, having comparable insufficiencies as grain products.^[2]

In assessing the digestability of the protein from 30 samples of hemp (hempseed either hulled or dehulled as well as seedmeal) using a rat bioassay and rating the score via PDCAAS noted a digestability of approximately 86.7% (the reference protein, casein, scored 97.6%) when looking at the seed meal.^[2] It appears that using dehulled seeds, prior to extraction of the oil, had a comparable absorption to casein (94.9+/-3.5%)^[2] and according to PDCAAS (reference of casein at 100) Hemp scored between 50 and 60, comparable to lentils, due to the deficient quantity of Lysine.^[2]

Hemp protein appears to be an incomplete amino acid source, but has decent protein absorption rates. Comparatively high in Arginine and Tyrosine and low in Lysine and Leucine

Hemp protein may be hydrolyzed via simulated gastric digestion, and some bioactives peptides appear to have antioxidative properties in in vitro oxidative assays (metal chelation, DPPH).^[13]

The two main cannabinoids in Hemp as a food product, Cannabidiol and its metabolite Cannabidiolic acid, are not agonists of the cannabinoid receptors (CB1 and CB2)^[14] although cannabidiol may be able to act as an inverse agonist at 1µM^[15] and impair the actions of other agonists at lower concentrations.^[15] As mentioned earlier, legally produced hemp must contain less than 0.3% Delta-9-THC by weight and is unlikely to confer the psychoactive properties of this molecule (which are causative of the known effects of Marijuana).

Due to depletion of THC, there are not any major intoxicating effects of hemp protein which would mostly be due to the THC content. Cannabidiol retains the potential to impair the activity of other agonists at the CB1 receptor

Hempseed extract, in vitro, appears to activate calcineurin in a concentration dependent manner with maximal activity at 10mg/mL increasing activity by 35+/-5%.^[6]

Oral ingestion of 200-800mg/kg hempseeds to mice for 7 days, where anti-memory agents (sodium nitrate, high acute dose of alcohol, and scopolamine) were introduced on days 8-10 during cognitive tested noted that preloading with all doses appeared to have anti-amnesiac effects (the best dose seemed to vary widely depending on test).^[6]

May have minor pro-cognitive effects at higher doses, bioactive mediating these effects is not yet known (if a cannabinoid, then it may be novel to hemp protein supplementation; if due to an amino acid, this may apply to protein in general)

A rat study using ovariectomized rats (research model of menopause) using 1%, 5%, or 10% hempseed in the diet appeared to reduce menopause-related anxiety at all groups in a dose-dependent manner relative to control; the increase in serum cholesterol (including HDL) and calcium seen in ovariectomized control was similarly reduced with hempseed ingestion.^[16]

At least one study suggests benefit to menopausal rats, active component not known

Hempseed has been investigated for its cardiovascular effects, particularly the fatty acid fragment.^[1] Dietary inclusion of hempseed at 5-10% expectedly gives rise to plasma omega-6 and omega-3 concentrations in animals and may reduced platelet aggregation secondary to that;^[17][18] an effect attributed to omega fatty acids in general.^[19]

The oil from hempseed given to otherwise healthy persons at 30mL on top of a regular diet for 4 weeks noted a reduction in triglycerides (1.23+/-0.64mmol/L to 1.03+/-0.44mmol/L) which was also observed with the other group given flaxseed; there was no observable change of HDL-C nor LDL-C with either treatment,^[20] and this lack of efficacy on LDL-C and HDL-C was replicated elsewhere with 12 weeks of hempseed oil ingestion at 2g daily (although this study also noted a lack of effect on triglycerides).^[21]

There may be minor heart protective effects secondary to reducing clotting potential, but these are attributed to the omega-6 and omega-3 fatty acid content (up to 10% in hempseed protein) and not solely unique to this product. Linoleic and Alpha-Linonelic acid are common fatty acids in nature

Cannabidiolic acid appears to be a selective COX-2 inhibitor, although fairly weak with an IC₅₀ of 2mM on COX-2 and 9.1-fold selectivity for COX-2 over COX-1.^[22]

Unlikely to be biologically relevant due to the high concentration required paired with the low oral intake of cannabidiolic acid in hempseed meal

Cannabidiolic acid and its parent molecule Cannabidiol appear to have anti-migration properties on invasive MDA-MB-231 cells, with 5μM ; this appeared to be independent of COX2 inhibition (noted with these molecules), and appears to be due to activation of RhoA due to inhibiting its phosphorylation (possibly downstream of PKA inhibition).^[8]

Oral ingestion of 30mL hempseed oil over 8 weeks relative to placebo (olive oil) in persons with atopic dermatitis noted that there was a trend to reduce transepidermal water loss (TEWL) in persons using hempseed from 12.2+/-5.3 at baseline to 9.6+/-3.7, although this failed to reach statistical significnace; the decrease in subjective skin dryness and itchiness did reach significance in the hempseed oil group.^[23]

Possible benefits against atopic dermatitis associated with the fatty acid fragment of hempseed oil, may not be unique to hempseed