PhosphatidylSerine & PhosphatidylCholine by InterPlexus

POSSIBLY EFFECTIVE

• Ulcerative colitis. Clinical research suggests that taking slow-release, phosphatidylcholine-rich phospholipids (Sterpur P-30 Granulat, Stern-Lecithin and Soja GmbH) improves symptoms and remission rate in patients with ulcerative colitis (68839,93389,93390,105728). A pooled analysis of 3 small randomized clinical trials in adults with chronic, active, ulcerative colitis at a single site shows that taking this specific form of phosphatidylcholine 1-4 grams daily for 3 months increases the odds of achieving clinical remission by 9.7 times when compared with placebo. Overall, 49% of the patients taking phosphatidylcholine achieved clinical remission. Taking phosphatidylcholine also improved quality of life and clinical improvement scores. In one study, this product also decreased the need for steroids, resulting in complete withdrawal of steroid therapy without exacerbation of disease in 80% of patients (93390). However, most patients in these studies were not treated with other standard therapies for ulcerative colitis, such as immunosuppressants and aminosalicylic acids. Subgroup analyses by dose suggest that the effective dose of this product is at least 1 gram daily; however, taking 3-4 grams daily may be more effective (93389,105728). In patients not responsive to mesalamine, some preliminary clinical research suggests taking LT-02 (Lipid Therapeutics GmbH), a modified-release formula of phosphatidylcholine, 3.2 grams daily for 12 weeks, improves symptoms of ulcerative colitis. Overall disease activity was improved by 52%, compared with 33% in those taking placebo. The effects on remission rate and mucosal healing were unclear; however, response rates were increased from 60% in the placebo group to 83% in the phosphatidylcholine group. In an 8-week follow-up, relapse was also less likely in patients treated with this product (93387).

POSSIBLY INEFFECTIVE

• Hepatitis A. Taking phosphatidylcholine orally does not seem to reduce serum bilirubin or liver enzyme levels in patients with hepatitis A (5225).
• Infant development. Clinical research suggests that taking phosphatidylcholine (PhosChol, Nutrasal) 5 grams daily, containing choline 750 mg daily, from 18 weeks' gestation to 90 days postpartum does not improve cognitive function in the infant at 10-12 months of age when compared with corn oil placebo (93386).
• Peritoneal dialysis. Taking phosphatidylcholine orally does not seem to improve ultrafiltration in peritoneal dialysis (5222).
• Tardive dyskinesia. Taking phosphatidylcholine orally does not seem to improve tardive dyskinesia (5223).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Preliminary clinical research suggests that topical application of a cream containing niacinamide and linoleic acid-rich phosphatidylcholine (4% niacinamide-phospholipidic; N-PHCL emulsion) once daily for 12 weeks appears to improve skin hydration and reduce acne lesions and inflammation when compared with a 1% clindamycin cream or a carrier-only cream in patients 15 years and older with moderate acne (93388).
• Alcohol-related liver disease. Preliminary clinical research suggests that taking polyunsaturated phosphatidylcholine 6 grams daily for 24 months does not increase survival compared to placebo in patients with acute alcoholic hepatitis (68843).
• Dementia. Population research in a sample of 1259 men in Finland found that those in the highest quartile of daily phosphatidylcholine intake have a 28% lower risk of being diagnosed with dementia than those in the lowest quartile, over a mean follow-up of about 22 years (103178).
• Fatty deposits. Preliminary clinical evidence suggests that subcutaneous injections of phosphatidylcholine can reduce localized fatty deposits on the chin, thigh, hips, abdomen, back, neck, and elsewhere, based on subjective visual assessments (15621,15625,15627). Improvements appear to last for 2-3 years or longer (15621,15627). In one study, phosphatidylcholine injections markedly or moderately reduce localized fatty deposits on the face in about 80% of patients for a period of up to 3 years based on subjective patient self-assessment (15621). The findings of these studies are severely limited by poor study quality.
• Hepatic encephalopathy. Clinical research suggests that taking polyunsaturated phosphatidylcholine 1050 mg daily for 6-8 weeks, either orally or through a nasogastric tube, does not improve recovery from encephalopathy compared with control in patients with acute or subacute liver failure. However, polyunsaturated phosphatidylcholine seems to reduce mortality compared to control in patients with subacute, but not acute, liver failure (68835).
• Hepatitis B. Clinical research using phosphatidylcholine for hepatitis B show conflicting results (5224,5226).
• Hepatitis C. Preliminary clinical research suggests that taking the polyunsaturated form of phosphatidylcholine orally, in combination with interferon, seems to help reduce liver enzymes in patients with chronic hepatitis C (5226).
• Hyperlipoproteinemia. Clinical research suggests that taking polyunsaturated phosphatidylcholine 1.8 grams daily for 28 days in combination with clofibrate does not significantly reduce total cholesterol, triglycerides, or phospholipids compared to clofibrate alone in patients with primary hyperlipoproteinemia of Fredrickson Types II or IV. However, taking the combination of polyunsaturated phosphatidylcholine plus clofibrate seems to significantly attenuate the relative increase in low-density lipoprotein (LDL) cholesterol compared to clofibrate alone (68840).
• Lipoma. An anecdotal report suggests that injecting a phosphatidylcholine solution directly into a lipoma can shrink the tumor by about 35%. However, in this report a major inflammatory reaction occurred, resulting in undesirable fibrotic changes to the tissue and eventual surgical excision of the lipoma (15622).
• Memory. Preliminary clinical evidence shows that taking a single dose of phosphatidylcholine 25 grams (PC-55, TwinLab) can improve some measures of memory in healthy college students (5228).
• Nonalcoholic fatty liver disease (NAFLD). Preliminary clinical research shows that taking phosphatidylcholine 600 mg orally three times daily for 24 weeks qualitatively improves liver echogenicity and structure on an ultrasound scan, suggesting a reduction in hepatic steatosis. There is also a small decrease in liver function test values, but with considerable variability both at baseline and at 24 weeks (103176,103177). Preliminary clinical evidence also suggests that taking a combination of the milk thistle constituent silybin, phosphatidylcholine, and vitamin E (Realsil, Instituto Biochimico Italiano) orally twice daily for 12 months improves liver function tests (LFTs) and liver histology in people with NAFLD (63244).
• Periorbital fat pad herniation. Preliminary clinical research suggests that injecting a phosphatidylcholine solution markedly reduces lower eyelid fat pads in people with bulging fat pads due to herniation. In some people, benefits appeared to last for a period of 9 months to 2 years or longer (15623,15628). More evidence is needed to rate phosphatidylcholine for these uses.

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POSSIBLY EFFECTIVE

• Age-related cognitive decline. Oral bovine cortex-derived phosphatidylserine seems to improve attention and memory in patients with age-related cognitive decline. It is unclear if plant-derived phosphatidylserine is beneficial or whether phosphatidylserine is beneficial for preventing cognitive decline. Details: Clinical studies in people with age-related cognitive decline show that phosphatidylserine improves attention, arousal, verbal fluency, and memory (2440,2441,7119,7120,15539). Bovine- and plant-sourced phosphatidylserine 100 mg three times daily for up to 6 months has been used in these studies (2440,2441,15539). Most clinical studies have used phosphatidylserine derived from bovine cortex. However, most supplements now use soy- or cabbage-derived phosphatidylserine. There is some preliminary evidence that plant-derived phosphatidylserine also improves memory in people with age-associated memory impairment (15539). Also, clinical research in elderly females with complaints of memory loss shows that taking 1-3 capsules of a specific product (Vayacog, Enzymotec Ltd.) containing soybean-derived phosphatidylserine 100 mg/capsule, enriched with docosahexaenoic acid (DHA) 19.5 mg/capsule and eicosapentaenoic acid (EPA) 6.5 mg/capsule, daily for 15 weeks modestly improves immediate memory and sustained attention when compared with placebo (66055,90711). A post-hoc analysis of the results from this study suggests that cognitive improvements are greatest in patients with relatively good cognitive performance at baseline (66055). There is also interest in using phosphatidylserine to prevent age-related cognitive decline. In 2003, the US Food and Drug Administration (FDA) determined that it would allow a qualified health claim stating that consuming phosphatidylserine may reduce the risk of developing age-related cognitive decline. However, the FDA has determined that there is very little scientific evidence supporting this claim (102363).
• Alzheimer disease. Oral bovine cortex-derived phosphatidylserine seems to improve cognitive function and behavior in patients with Alzheimer disease when used for up to 12 weeks, although benefits may disappear after 16 weeks. It is unclear if plant-derived phosphatidylserine is beneficial. Details: Taking phosphatidylserine orally can improve cognitive function and global improvement rating scales and improve behavioral rating scales over 6-12 weeks of treatment (2255,2437,2438,2439,7114,7118). Bovine-sourced phosphatidylserine 300-400 mg in divided doses daily for up to 16 weeks has been used (2255,2437,2438,2439). Phosphatidylserine seems to be most effective in patients with less severe symptoms (2437,2439). Phosphatidylserine might lose its effectiveness with extended use. After 16 weeks of treatment, progression of Alzheimer disease seems to overcome any benefit of phosphatidylserine (2255). Most clinical studies have used phosphatidylserine derived from bovine cortex. However, most supplements now use soy- or cabbage-derived phosphatidylserine. Clinical studies have not yet evaluated phosphatidylserine from soy or other sources. It is not known if phosphatidylserine from these sources is as effective as bovine-derived products.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. It is unclear if oral phosphatidylserine is beneficial for athletic performance. Details: One small clinical trial in golfers shows that taking nutritional bars containing phosphatidylserine 200 mg daily for 6 weeks improves the number of good ball flights, which may improve golf score; however, perceived stress levels and heart rate are not significantly affected (68855). A clinical study in recreationally active adults shows that taking phosphatidylserine 400 mg and caffeine 100 mg daily, along with niacin 28 mg, vitamin C 60 mg, vitamin B1 1.5 mg, vitamin B5 10 mg, vitamin B6 2 mg, vitamin E 12 IU, calcium 100 mg, magnesium 40 mg, and carbohydrates in the form of evaporated cane juice, brown rice syrup, and rice syrup solids 16 grams (Nutravail Technologies) for 14 days modestly reduces post-exercise mood disturbances and perception of fatigue when compared with vitamins and minerals alone. The combination does not appear to improve cognitive function or reaction time (91463). It is not clear if the effect of the combination supplement is due to phosphatidylserine, caffeine, or the combination.
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral phosphatidylserine is beneficial for ADHD. Details: A meta-analysis of three generally low-quality randomized clinical trials shows that taking phosphatidylserine 200-300 mg daily for 8-15 weeks modestly improves symptoms of inattention in children with ADHD when compared with placebo. However, there were no significant effects on hyperactivity-impulsivity or on overall ADHD symptoms. Also, two of the three clinical trials included in the analysis investigated the effects of phosphatidylserine in combination with the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (105247). One preliminary clinical trial included in the analysis shows that taking soy-derived phosphatidylserine 200 mg daily for 2 months improves ADHD symptoms, including inattention, hyperactivity-impulsivity, and short-term memory, when compared to baseline in treatment-naïve children with ADHD aged 4-14 years. However, results from this study are limited due to a lack of statistical comparison to the placebo group (89498).
• Cognitive function. Although there is interest in using oral phosphatidylserine for improving cognitive function in healthy adults, there is insufficient reliable information about the clinical effects of phosphatidylserine for this purpose.
• Dementia. It is unclear if oral phosphatidylserine is beneficial for dementia prevention or treatment. Details: In 2003, the FDA determined that it would allow a qualified health claim stating that consuming phosphatidylserine may reduce the risk of dementia in the elderly. However, the FDA has determined that there is very little scientific evidence supporting this claim (102363).
• Depression. It is unclear if oral phosphatidylserine is beneficial for depression. Details: One very small clinical study in elderly adults with depression shows that taking phosphatidylserine 300 mg daily for 30 days modestly improves depression scores when compared to baseline (7113).
• Exercise-induced muscle soreness. It is unclear if oral phosphatidylserine is beneficial for exercise-induced muscle soreness. Details: One small clinical study in athletes shows that taking soybean-derived phosphatidylserine 800 mg daily for 2 weeks during periods of over-training reduces muscle soreness post-exercise when compared with those not taking phosphatidylserine (2264). More evidence is needed to rate phosphatidylserine for these uses.

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POSSIBLY SAFE ...when used orally and appropriately. Large doses up to 30 grams per day for 6 weeks (5223) and smaller doses of up to 6 grams daily for up to 24 months have been well tolerated (68839,68843,105728). ...when used subcutaneously and appropriately, short-term. Some research suggests that subcutaneous injections of 0.2 mL to 5 mL of a 5% phosphatidylcholine solution do not cause significant serious adverse effects when doses are administered up to five times and spaced apart by 2-4 weeks (15621,15623,15624,15625). ...when used topically as an emulsion also containing niacinamide for up to 12 weeks (93388).

PREGNANCY: POSSIBLY SAFE
when used orally from 18 weeks of gestation at doses of up to 5 grams daily (93386)

LACTATION:
Insufficient reliable information available; avoid using.

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POSSIBLY SAFE ...when used orally and appropriately. Phosphatidylserine has been used with apparent safety at dose of up to 300 mg daily for up to 6 months (2255,2437,2438,2439,2440,2441,7118,15539,68855).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term (7117). Phosphatidylserine has been used with apparent safety in clinical research in doses of 200-300 mg daily for up to 4 months in children aged 4-18 years (7117,89498).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, phosphatidylserine might decrease the effectiveness anticholinergic drugs.  Details Phosphatidylserine is thought to increase acetylcholine levels (2437,8857,8858), which could theoretically interfere with the activity of anticholinergic agents.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, phosphatidylserine might have additive effects with cholinergic drugs.  Details Phosphatidylserine is thought to increase acetylcholine levels (2437,8857,8858), which could theoretically lead to additive cholinergic effects when used with cholinergic drugs.

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General ...Phosphatidylcholine is generally well tolerated when used orally, subcutaneously, or topically. Orally, bloating, diarrhea, altered taste, nausea, vomiting, sweating, and itching have been reported with phosphatidylcholine (5229,63244,68843,93389,93390,105728). Ingesting large amounts of around 30 grams daily is associated with a higher incidence of gastrointestinal upset and diarrhea (5223). Subcutaneously, pain, burning, itching, tenderness to touch, bruising, edema, nodules, hematoma, and erythema at the injection site have been reported with phosphatidylcholine (1562,15623,15624,15625,15626,15627,15628). High subcutaneous doses exceeding 1.2 grams of phosphatidylcholine can cause nausea and abdominal pain in some people (15624). Injecting phosphatidylcholine directly into a lipoma can result in a significant inflammatory response and undesirable fibrotic tissues changes (15622).

Dermatologic ...When taken orally, phosphatidylcholine may increase sweating (5229) and itching (63244). When given subcutaneously, phosphatidylcholine can cause pain, burning, itching, tenderness to touch, bruising, edema, and erythema at the injection site. The pain, itching and erythema usually resolve within 2 days of treatment; however localized tenderness can last longer (15623,15624,15626,15627,15628). Edema and bruising usually resolve within 10 days of treatment (15621,15623,15625). Some people can also develop nodules or hematoma at the injection site. This usually resolves within 30 days (15627).

Gastrointestinal ...Ingesting large amounts of phosphatidylcholine (30 grams per day) can cause gastrointestinal upset and diarrhea (5223). However, bloating, diarrhea, altered taste, nausea, and vomiting have been reported with smaller doses (63244,68843,93389,93390,105728). Although moderate subcutaneous doses do not usually cause systemic side effects, high doses exceeding 1.2 grams of phosphatidylcholine can cause nausea and abdominal pain in some people (15624).

Musculoskeletal ...Injecting phosphatidylcholine directly into a lipoma can result in a significant inflammatory response and undesirable fibrotic tissue changes (15622).

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General ...Orally, phosphatidylserine is generally well tolerated.
Most Common Adverse Effects:
Orally: Flatulence, gastrointestinal upset, headache, insomnia, and nausea.

Gastrointestinal ...Orally, phosphatidylserine can cause gastrointestinal upset such as flatulence or nausea. Gastrointestinal upset can occur at doses of 200-300 mg/day (7116,7121,15539,68862,90711).

Neurologic/CNS ...Orally, phosphatidylserine can cause insomnia. Insomnia is more likely to occur with a higher dose of 600 mg (7121,68844). Headache has also been reported (90711).

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