Chlorella

1.1. Sources

Chlorella is a unicellular fresh water algae, known for being a vegan source of both iron and bioavailable B12 (cobalamin), which is one of the few green algaes to possess a bioactive B12 form alongside porphyra yezoensis (Nori)^[2][3] and pleurochrysis carterae.^[4] Consuming these seaweed sources in the diet is associated with higher serum B12 concentrations in vegans when compared to vegans not consuming seaweed products.^[5]

1.2. Composition

Chlorella (the genus) tends to contain the macronutrient profile of:

• Lipids (Fatty Acids) at 12.0+/-0.56% dry weight at the low end, but sometimes estimated as high as 28-32% dry weight,^[6] containing some saturated fatty acids (myristate, palmitate, laurate).^[7] Lipids may be lost by over 70% during the process of pigment removal (bleaching) with activated clay^[8]

• Protein (chlorella pyrenoidosa) relatively high in leucine (7.3% total protein^[9]) and glutamate (9% total protein^[9])

Noncaloric micronutrients found in chlorella species include:

• Chlorophyll at 1.3% dry weight of chlorella vulgaris^[8]

• Active Vitamin B12 at 205-223mcg/100g (Cobalamin) ^[10], unlike Spirulina which does not have active B12 but instead 7-adenyl cyanocobamide (pseudovitamin B12)^[11]

1.3. Formulations and Variants

Chlorella vulgaris tends to be sold as 'Broken Cell Wall' chlorella.

For the major purpose of chlorella supplementation, an apparent detoxification of heavy minerals, limited evidence in mice suggest that breaking the cell wall is not necessary.^[12]

2.1. Cellular Kinetics

One in vitro study investigating the efficacy of chlorella in inhibiting the Breast Cancer Resistance Protein (BCRP), an efflux transporter whose inhibition may augment chemotherapy, found that Chlorella exerted moderate to weak inhibition at 22.4% of control at 1mg/mL; it was outperformed by Milk Thistle, rutin, and soybean extract at the same dosages while the active control of 5µM fumitremorgin was as effective as Soy and Rutin but outperformed all others.^[13]

2.2. Mineral Detoxification

Among plants, chlorella vulgaris as a plant is able to bioaccumulate heavy metals (as assessed by hexavalent chromium) to a larger degree than its environment^[14] which is a common property for algae in general^[15] with chlorella vulgaris being noted to accumulate up to 3,579.01μg/g heavy metal in a medium containing 100μg/mL hexavalent chromium.^[14] Other studies assessing the bioaccumulation properties of chlorella species have noted success with accumulating arsenic^[16][17] and mercury.^[18]

When looking in vitro, most algae appears to be able to accumulate metals from their surroundings to a large degree. Chlorella is implicated in this, being able to bioaccumulate heavy metals to a large degree

In mice, the chlorella source of parachlorella beijerinckii (CK-5 strain with walls intact) given to pregnant mice at 10% of the diet alongside intentional mercurcy contamination noted that the chlorella group was associated with mildly less mercurcy accumulation in the blood (15%) and brain (13.5%) of the mother with less in blood, brain, liver, and the kidney of the fetus after birth.^[12] This enhancement of mercury removal from mice has been noted elsewhere at half the dose (5% of the diet) in as little as 21 days^[19] and 100mg acutely (5,400mg/kg; estimated human equivalent of 430mg/kg) alongside a high dose of mercury (5mg/kg) has been noted to increase fecal and urinary mercury elimination in mice relative to control.^[20]

High doses of a particular strain of chlorella known as parachlorella beijerinckii CK-5 appear to have mouse evidence for increasing mercury removal from the organism following oral ingestion. This requires feasible yet high oral doses, and it is not confirmed if this extends to chlorella vulgaris (the major supplemental form of chlorella)

3.1. Anemia

Pregnancy is associated with Anemia in approximately 18% of women industrialized countries (not recent statistics)^[21] although recently has been pinpointed at 17-22% in Japan.^[22] It has previously been reported in rats that diets with chlorella (5-10%) were capable of increasing erythrocytic (red blood cell) iron content and aid the state of anemia^[23] and these results were replicated in pregnant women given 6g of Chlorella from some time point between gestation weeks 12-18 until delivery, where Chlorella was associated with significantly higher Hemoglobin (+5.6%), Hematocrit (+6.3%), and Red Blood Cell count (+4.7%) compared to control (unblinded).^[24] The amount of women remaining above a 11g/dL threshold for hemoglobin concentration was significantly enhanced with Chlorella, and no influence on blood pressure was noted.^[24]

3.2. Blood Pressure

One study investigating a GABA rich Chlorella supplement (500mg/100g) in hypertensive persons (systolic 130-159mmHg) given 10g Chlorella delivering 20mg GABA noted that over 12 weeks Chlorella was associated with lower systolic and diastolic blood pressure from week 4 onward, with more potency in persons with higher blood pressure at baseline.^[25] These results were building off a previous dose-response study in humans where the same GABA-rich Chlorella extract was associated with significant reductions in blood pressure in a hypertensive population.^[25]

Other studies that make note of blood pressure changes note no significant effect on pregnant women using 6g Chlorella daily until delivery^[24] and a lowering of systolic blood pressure in male smokers (6.3g Chlorella) that failed to reach statistical significance.^[26]

4.1. Neuroinflammation

After chronic oral consumption to rats, less astrocytic activation in the hippocampal CA1 region has been noted; indicative of antiinflammatory effects.^[27]

4.2. Cognition

One study in mice assessing cognition (via Morris Water-Maze) noted that Chlorella was ineffective in young rats regardless of mouse strain (DAL101 or C57BL/6) but suppressed the decline in memory (spatial and visual recognition) associated with premature aging in DAL101.^[27]

5.1. Mechanisms

A study in persons with signs of metabolic syndrome that measured genomic changes in response to supplementation of Chlorella noted variations in mRNA transcription involved in insulin signalling (such as the receptor itself and PTP1B) but did not precisely quantify these changes,^[28] it appeared genes involved in insuling signalling and glucose uptake (GLUT4, Akt) were enhanced while supressive proteins (PTP1B) were suppressed within the range of 0.5-2.0fold basal activity, and these were said to possibly explain the small but statistically significane reduction in blood pressure seen with Chlorella.^[28]

6.1. Fibromyalgia

10g of Chlorella taken daily for 2 months was associated with a 22% decrease in pain (assessed by TPI) in one pilot study in 18 persons with Fibromyalgia.^[29] This study required participants to have a Tender Point Index (TPI) of 22 or greater, and the average TPI of 32 at baseline decreased to 25 after 2 months and two patients noted more than 50% improvement^[29] (study duplicated in Medline^[30]).

7.1. General Immunity

One intervention using a crossover design noted that 4 weeks of Chlorella supplementation at 6g daily was able to increase salivary Immunoglobulin A concentrations,^[31] suggesting it may play a role in protecting against respiratory tract infections due to IgA's importance^[32] and significant inverse correlation to infection.^[33][34] Interestingly, increased Immunoglobulin A has also been found in the breast milk of mothers consuming Chlorella during their pregnancy.^[35]

7.2. Vaccination

One study has been conducted with 200 or 400mg Chlorella supplementation for a period of 3 weeks prior to undergoing vaccination and for 7 more days, and noted that Chlorella supplementation failed to augment the antibody response to vaccination.^[36]

One study that had no control group, but used Chlorella (9g daily; two doses of 4.5g) in either healthy persons or obese persons with symptoms similar to metabolic syndrome over a period of 12 weeks (with 4 monitored weeks thereafter) noted that there was a statistically significant reduction in body fat at week 12 in both groups, which was attenuated by week 16; the decrease was not apparent at weeks 0-8.^[28]

One study investigating the immune system but also measuring anthropometric measures noted that 4 weeks of supplementation of 6g chlorella to otherwise healthy non-obese adult men failed to modify either lean mass or fat mass.^[31] This has also been noted with a higher dose (10g) of GABA-rich Chlorella over a period of 12 weeks.^[25]

Interventions suggest either no effects, or clinically insignificant effects (small magnitude) that disappear with cessation; Chlorella is not apparently anti-obese or pro-fat loss

9.1. Estrogen

In vitro, Chlorella shows some ability to metabolize more potent estrogens (estradiol) to lesser potent forms such as estrone and an unknown metabolite; unknown if this can occur in vivo .^[37] This biodegradation has been noted elsewhere^[38] and may extend to other phenolic compounds with structural similarity like Bisphenol-A.^[39]

Appears to be able to degrade estrogens and xenoestrogens outside of the body, but whether these abilities carry over into the body is unknown (and likely doubtful, as light sensitivity implicates enzymes that may be degraded after digestion)

10.1. Kidneys

One study in pregnant women noted that 6g of Chlorella was associated with less urinary proteins, suggesting a renoprotective effect; mechanisms unknown.^[24]

10.2. Lungs

One study conducted in moderate to heavy drinking Korean Smokers (tobacco) given 6.3g Chlorella daily for 6 weeks noted an increase in serum Vitamin C (44.4%) and Vitamin E (15.7%), as well as two antioxidant enzymes in red blood cells (catalase by 5.5% and superoxide dismutase by 17.5%).^[26] Alpha and Beta-carotenes as well as red blood cell Glutathione Peroxidase did not change significantly, and this was thought to be secondary to preservation of systemic anti-oxidants from Chlorella's inherent anti-oxidant capabilities, although Chlorella itself has a Vitamin E content.^[26] DNA damage measured in lymphocytes decreased in both Chlorella and placebo.

11.1. Detoxification

One study has been conducted on the environmental estrogen Dioxin noting an inverse relationship between oral Chlorella intake in mothers and reduced Dioxin concentration in breast milk; although Immunoglobulin A was higher in the breast milk of the Chlorella group, this was not associated with Dioxin.^[35]

11.2. Pregnancy

One human study has been conducted with 6g Chlorella during pregnancy from gestational week 12-18 (variable start date) until delivery, and was generally well tolerated with no reported adverse effects on mother or apparent adverse effects on offspring.^[24]

Interestingly, toxicological reports indicate that Chlorella is associated with less leg edema (water retention and swelling) at 6g daily relative to control; with 44.7% of women in control reporting leg edema in the third trimester yet only 9.4% reporting edema with 6g Chlorella.^[24] Some changes were apparent in the second trimester (6.3% v. 18.4%) but were not statistically significant.

11.3. General

Some human and animal interventions note green discoloration of feces due to the chlorophyll content of Chlorella, seen as benign and has been noted at 6g daily.^[24] At this dose, loose stools and diarrhea are noted at times but are brief and clinically insignificant.^[25]